Coadministration of abacavir and lopinavir/ritonavir has no effect on lopinavir or ritonavir pharmacokinetics, but appears to decrease abacavir exposure by ~30%. The clinical significance of this is unknown.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abatacept is a fusion protein consisting of the extracellular domain of human CTLA-4 linked to a modified Fc portion of human IgG1 and is likely to be eliminated via proteolytic catabolism throughout the body. Lopinavir/ritonavir is metabolized by CYP3A4.

Coadministration has been studied and is not recommended. Abemaciclib is metabolized by CYP3A4 and is a substrate of P-gp and BCRP. Clarithromycin (a strong CYP3A4 inhibitor) increased abemaciclib AUC by 3.4-fold and increased the AUC of abemaciclib with its three active metabolites by 2.2-fold. A similar effect is expected with lopinavir/ritonavir. Furthermore, lopinavir may cause QTc interval prolongation. No large QTc prolonging effect has been observed for abemaciclib, but the net effect on QT prolongation has not been reported and it is unknown whether there is a warning in place. Coadministration should be avoided if possible. If concurrent use is unavoidable, adjust the dose of abemaciclib to 50 mg once daily with close monitoring for signs of toxicity. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely. Abiraterone is metabolized by CYP3A4 and SULT2A1. A 15% increase in abiraterone exposure has been reported in presence of ketoconazole (a strong CYP3A4 inhibitor) and a similar effect is expected with lopinavir/ritonavir, but this is not considered to be clinically relevant. However, caution should be exercised as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir/ritonavir and conditional risk for abiraterone). Considering the modest pharmacokinetic interaction, the risk of a QT interval prolongation is low.

Coadministration has not been studied. Abrocitinib is metabolised predominantly by CYP2C19 and CYP2C9, and to a lesser extent by CYP3A4 and CYP2B6. Lopinavir/ritonavir inhibits CYP3A but induces CYP2C19 and CYP2C9, the main enzymes contributing to abrocitinib metabolism, and could potentially decrease abrocitinib exposure. The product label for abrocitinib does not recommend coadministration with moderate or strong inducers of both CYP2C19 and CYP2C9 and therefore coadministration should be avoided.

Coadministration has not been studied but should be avoided. Acalabrutinib is metabolized by CYP3A4. Itraconazole (a CYP3A4 inhibitor) increased acalabrutinib AUC and Cmax by 5.1- and 3.9-fold, respectively. A similar effect may occur with lopinavir/ritonavir. Increased acalabrutinib concentrations may result in increased toxicity, therefore, coadministration should be avoided.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acamprosate is eliminated unchanged in the urine.

Coadministration has not been studied. Acenocoumarol is mainly metabolized by CYP2C9 and to a lesser extent by CYP1A2 and CYP2C19. In vitro and in vivo data indicate that lopinavir/ritonavir is a weak inducer of CYP2C9. Lopinavir/ritonavir could potentially decrease acenocoumarol concentrations. Monitor INR.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acetazolamide is primarily excreted unchanged via the kidneys, there is therefore little potential for interaction with lopinavir/ritonavir via modulation of, or competition for metabolic pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aclidinium bromide is rapidly and extensively hydrolyzed (non-enzymatic and enzymatic transformation by esterases and butylrylcholineesterases) to its pharmacologically inactive metabolites with only a minor role for CYP metabolism.

Coadministration has not been studied. Activated charcoal absorbs substances in the stomach and intestines and may decrease absorption of orally administered medicines. If coadministration is required, administration of activated charcoal and lopinavir/ritonavir should be separated by 4 hours. [Note: this interaction is not specific for lopinavir/ritonavir, but for any oral medication taken with activated charcoal.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Adalimumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Adrenaline is rapidly inactivated, mostly in the liver by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). There is therefore little potential for interaction with lopinavir/ritonavir via modulation of, or competition for metabolic or elimination pathways.

Coadministration has not been studied. Afatinib is mainly eliminated unchanged in the faeces and is a substrate of P-glycoprotein and BCRP. Administration of ritonavir (200 mg twice daily for 3 days) 1 hour before afatinib (20 mg single dose) increased afatinib AUC and Cmax by 48% and 39%. However, coadministration of ritonavir simultaneously or 6 hours after afatinib (40 mg) resulted in minimal increase in afatinib AUC and Cmax (19% and 4% for simultaneous administration; 11% and 5% for the staggered administration). The European product label for afatinib recommends to administer strong P-gp inhibitors (such as lopinavir/ritonavir) 6 hours apart from afatinib. The US product label includes a recommendation to decrease afatinib daily dose by 10 mg if not tolerated for patients who require a therapy with a P-gp inhibitor.

Coadministration of lopinavir/ritonavir (400/100 mg twice daily) and African potato was studied in 16 HIV-negative subjects. Relative to repeated administration of lopinavir/ritonavir alone, steady-state Cmax and AUC of lopinavir remained unchanged following concomitant administration of multiple-dose African potato. These results suggest that inhibition of CYP3A4 by ritonavir offsets any inducing effect of African potato on CYP3A4 expected when used for extended periods. 

Coadministration has not been studied. Agomelatine is metabolised predominantly by CYP1A2 which is induced by lopinavir/ritonavir. Coadministration could potentially decrease agomelatine exposure. Monitor clinical effect and increase dosage if needed.

Coadministration has not been studied. In vitro studies have demonstrated that CYP3A4 and the flavine-containing monooxygenase system are involved in formation of the active metabolite albendazole sulfoxide. Short term (2 doses) coadministration with ritonavir (200 mg) did not impact albendazole pharmacokinetics whereas long-term coadministration (8 days) decreased albendazole exposure likely due to ritonavir inducing effect. Lopinavir/ritonavir is unlikely to significantly affect albendazole exposure when used for a short duration treatment but may reduce the clinical effect of albendazole when used for a long duration treatment.

Albuvirtide is a peptide which is eliminated by catabolism to its constituent amino acids. Coadministration of albuvirtide (320 mg once weekly intravenous) and oral lopinavir/ritonavir (400/100 mg twice daily) was evaluated in HIV-infected individuals. Albuvirtide exposure was not significantly affected by lopinavir/ritonavir. However, both lopinavir and ritonavir concentrations were lower in presence of albuvirtide compared with lopinavir/ritonavir alone (lopinavir AUC, Cmax and Ctrough decreased by 37%, 33% and 35%, respectively; ritonavir AUC, Cmax and Ctrough decreased by 38%, 39% and 28%, respectively). The mean lopinavir Ctrough in presence of albuvirtide (7.1 µg/ml) remained higher than the minimal lopinavir Ctrough previously associated with efficacy. Furthermore, a randomized, phase 3 study (TALENT study) showed that albuvirtide + lopinavir/ritonavir was non-inferior to the standard second-line regimen lopinavir/ritonavir + zidovudine/tenofovir disoproxil fumarate + lamivudine in HIV infected Chinese individuals suggesting that this interaction has no clinical consequences. In vitro human microsomal studies indicate that albuvirtide has no inducing properties on P450 enzymes. In addition, albuvirtide binds to <1% of serum albumin in the range of clinical concentrations, thus the observed decrease in lopinavir and ritonavir concentrations is unlikely to result from protein binding displacement. However, binding of the albuvirtide-albumin complex to the HIV protease inhibitor cannot be excluded.

Coadministration has not been studied. Alcohol is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase. The chronic use of alcohol may induce CYP2E1 and to a lesser extent CYP3A4. No a priori clinically relevant drug-drug interaction is anticipated with lopinavir/ritonavir TABLETS. However, coadministration with lopinavir/ritonavir ORAL SOLUTION is not recommended as the large amount of propylene glycol in the oral solution may compete with alcohol for the same elimination pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alcuronium is predominantly eliminated unchanged via the kidneys.

Coadministration has not been studied. Alectinib is metabolised by CYP3A4 to an active metabolite (M4), which is also metabolised by CYP3A4. Alectinib does not inhibit CYP3A4 to a clinically relevant extent. Concentrations of alectinib and M4 may increase due to inhibition of CYP3A4 by lopinavir/ritonavir, although to a modest extent. Posaconazole (a strong CYP3A inhibitor) had only a minor effect on the combined exposure of alectinib and M4 (7% decrease in Cmax; 36% increase in AUC). Monitoring for alectinib toxicity should be considered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alemtuzumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Lopinavir/ritonavir is metabolized by CYP3A4. CYP-mediated drug interactions are not expected with alemtuzumab. Note, use of alemtuzumab (marketed as Lemtrada) for the treatment of relapsing remitting multiple sclerosis is contraindicated in patients with HIV infection as it causes prolonged reductions of CD4+ lymphocyte counts.

If taken at the same time, it is likely that food and beverages (including mineral water), calcium supplements, antacids, and some oral medicinal products will interfere with absorption of alendronate. Therefore, patients must wait at least 30 minutes after taking alendronate before taking any other oral medicinal product.

Coadministration is contraindicated as it may increase alfuzosin concentrations which may lead to severe hypotension. Furthermore, both drugs have a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied and is not recommended. Aliskiren is minimally metabolized by CYP450, however, P-gp is a major determinant of aliskiren bioavailability. A 5-6 fold increase in exposure was observed with itraconazole 100 mg twice daily (a CYP3A4 and P-gp inhibitor) and a similar interaction is possible with lopinavir/ritonavir (due to inhibition of P-gp by ritonavir). The product labels for aliskiren recommend avoiding concomitant use with CYP3A4 and P-gp inhibitors.

Coadministration has not been studied. Almotriptan is partly eliminated unchanged in the urine and partly metabolized (mainly via monoamine oxidase-A and to a lesser extent by CYP3A4, CYP2D6 and flavin monooxygenase). Coadministration may increase almotriptan concentrations due to inhibition of CYP3A4. The American product label for almotriptan recommends using an initial almotriptan dose of 6.25 mg with a strong CYP3A4 inhibitor and not exceeding 12.5 mg within a 24 hour period. It also recommends to avoid use of almotriptan and a strong CYP3A4 inhibitor in patients with impaired renal or hepatic function.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Aloe vera is only a weak inhibitor of CYPs in vitro and therefore is unlikely to cause clinically significant interactions. It does not inhibit P-gp and there is no evidence to suggest it impacts UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alogliptin is primarily excreted unchanged in the urine and undergoes negligible CYP-mediated metabolism. Alogliptin was shown to have no inhibitory or inducing effect on CYPs at concentrations achieved with the recommended dose of 25 mg alogliptin.

Coadministration has not been studied. In vitro data indicate that alosetron is metabolized by CYPs 2C9 (30%), 3A4 (18%) and 1A2 (10%); however, in vivo data suggest that CYP1A2 plays a more prominent role. In vivo data indicate that lopinavir/ritonavir induces CYP1A2, therefore coadministration with lopinavir/ritonavir could potentially decrease alosetron exposure.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Alpelisib is primarily metabolized by enzymatic hydrolysis to an inactive metabolite, with a minor contribution from CYP3A4. Lopinavir/ritonavir is a strong inhibitor of CYP3A4 and may increase alpelisib concentrations. However, no clinically significant effect is expected as CYP3A4 represents a minor pathway in alpelisib metabolism. A PBPK model predicted coadministration of ritonavir (100 mg twice daily) to increase alpelisib AUC by 1.16-fold. No dose adjustment of alpelisib is necessary and standard dosing can be continued

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following administration, ~80% of circulating alprostadil is rapidly metabolised in the lungs primarily by beta- and omega- oxidation and the resulting metabolites are mainly excreted in urine. Lopinavir/ritonavir is metabolised by CYP3A4. Alprostadil is unlikely to affect CYP enzymes.

Coadministration has not been studied. Ambrisentan is mainly glucuronidated by UGT1A9, UGT2B7, UGT1A3 and is metabolized to a lesser extent by CYP3A4. Ambrisentan is also a substrate of P-gp and OATP1B1. Ambrisentan concentrations may increase due to inhibition of OATP1B1 by lopinavir/ritonavir. Start ambrisentan at 5 mg and closely monitor the patient for tolerability.

Coadministration has not been studied. Aminophylline is a complex of theophylline and ethylenediamine and is given for its theophylline activity. Theophylline is mainly metabolized by CYP1A2 and in vitro data indicate that lopinavir/ritonavir induces CYP1A2. Lopinavir/ritonavir could potentially decrease theophylline concentrations. Monitor plasma concentrations and increase aminophylline dosage if needed.

Coadministration has not been studied. Amiodarone is metabolised by CYP3A4 and concentrations may be increased due to inhibition of CYP3A4 by lopinavir/ritonavir. Coadministration is contraindicated in European SPC but the US Prescribing Information suggests caution and concentration monitoring (if available). Furthermore, both drugs have a  risk of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; known risk for amiodarone). Caution should be exercised if coadministered. ECG monitoring is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amisulpride is weakly metabolized and is primarily eliminated renally (possibly via OCT).

Coadministration has not been studied. Amitriptyline is metabolised predominantly by CYP2D6 and CYP2C19. Lopinavir/ritonavir could potentially increase amitriptyline exposure although to a moderate extent. No a priori dosage adjustment is recommended but monitor adverse effects. Note, both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; conditional risk for amitriptyline which may be increased in presence of an interacting drug like lopinavir/ritonavir). ECG monitoring is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Amivantamab is a monoclonal IgG1 and is eliminated primarily via intracellular catabolism similarly to endogenous IgG. Lopinavir/ritonavir is metabolized by CYP3A4.

Coadministration has not been studied. Amlodipine is metabolized by CYP3A4. Lopinavir/ritonavir is predicted to increase amlodipine exposure by ~2-fold based on drug-drug interactions studies with amlodipine and indinavir/ritonavir or paritaprevir/ritonavir. If coadministration is indicated, consider a dose reduction for amlodipine of 50%. Use with caution as both lopinavir/ritonavir and calcium channel blockers prolong the PR interval. Close monitoring is recommended.

Coadministration has not been studied. Amodiaquine is metabolized mainly by CYP2C8 to N-desethylamodiaquine, an active metabolite but less potent than the parent compound. Ritonavir dosed as a pharmacokinetic booster is a weak inducer of CYP2C8. Lopinavir/ritonavir could potentially decrease amodiaquine exposure, although to a moderate extent. However, coadministration of lopinavir/ritonavir and amodiaquine decreased desethylamodiaquine exposure by 51%. This drug-drug interaction was unexpected and the related mechanism is unclear. No a priori dosage adjustment is recommended.

Coadministration has not been studied. Amphetamine is metabolized by CYP2D6 and coadministration could potentially increase amphetamine exposure, although to a moderate extent. However, as dosing of recreational drugs can be variable, caution is advised.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ampicillin is predominantly eliminated unchanged via renal pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Anakinra is an IL-1 receptor antagonist which is predominantly cleared renally by glomerular filtration and subsequent tubular metabolism. Lopinavir/ritonavir is metabolized by CYP3A4. Patients requiring treatment with anakinra may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Anakinra, per se, has no inhibitory or inducing effects on cytochromes. Anakinra will normalize cytochrome activity (via inhibition of IL-1) but no significant effect on lopinavir/ritonavir is expected and no a priori dose adjustment is required.

Coadministration has not been studied. Anastrozole is mainly oxidized to hydroxyanastrozole by CYP3A4 (major) and glucuronidated by UGT1A4. The magnitude of the interaction is predicted to be of moderate intensity as ritonavir has an opposite effect on CYP3A4 (inhibition) and UGT1A4 (induction), which might result in a counterbalancing effect. No a priori dosage adjustment is recommended.

Lopinavir/ritonavir can be coadministered with acid reducing agents with no dose adjustment. No reduction in lopinavir or ritonavir trough concentrations were observed over 48 weeks in HIV+ subjects receiving lopinavir/ritonavir with an acid reducing agent (antacids, proton pump inhibitors or H2 receptor antagonists).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Thymoglobulins are cleared by the reticuloendothelial system.

Coadministration has not been studied but should be avoided. Apalutamide is primarily metabolized by CYP2C8 and CYP3A4. Apalutamide concentrations may increase as lopinavir/ritonavir inhibits CYP3A4. In addition, lopinavir/ritonavir is metabolized by CYP3A4 and apalutamide is a strong inducer of CYP3A4. Coadministration of apalutamide with midazolam (a CYP3A4 substrate) decreased midazolam AUC by 92%. A significant decrease in lopinavir/ritonavir exposure is expected after coadministration with apalutamide, leading to loss of therapeutic effect and possible development of resistance. Furthermore, lopinavir has a possible QT risk and androgen deprivation therapy may prolong the QT interval.

Coadministration has not been studied. Concentrations of apixaban are expected to increase due to potent CYP3A4 and P-gp inhibition by lopinavir/ritonavir, thereby increasing the bleeding risk. The product labels for apixaban do not recommend the concomitant use with strong dual CYP3A4 and P-gp inhibitors, although the US label gives the option to use apixaban at a reduced dose if needed. Note, patients already receiving apixaban at a dose of 2.5 mg twice daily should avoid coadministration with strong dual CYP3A4 and P-gp inhibitors. Of interest, there are case reports of no adverse outcomes in HIV infected patients treated with a reduced dose of apixaban (2.5 mg twice daily) while on ritonavir or cobicistat boosted regimens which supports the option of dose reduction given in the US label.

Coadministration has not been studied. Apomorphine is metabolized by several pathways that include mainly glucuronidation and sulfation and to a lesser extent N-demethylation. Although protease inhibitors have the potential to induce glucuronidation, the clinical relevance of such an interaction is unknown considering the numerous pathways contributing to apomorphine metabolism. No a priori dosage adjustment is required. However, the European SPC for lopinavir advises caution when coprescribing with drugs known to induce QT interval prolongation. Apomorphine has a possible risk of QTc prolongation on the CredibleMeds.org website. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Apremilast is metabolized by multiple pathways involving hydrolysis, glucuronidation and oxidation by CYP3A4. Coadministration of apremilast with ketoconazole (a strong CYP3A4 inhibitor) increased apremilast AUC by 36%. This effect is not considered to be clinically significant and does not warrant a dosage adjustment of apremilast. Similarly, lopinavir/ritonavir is unlikely to significantly alter apremilast exposure. Furthermore, apremilast has no inhibitory or inducing effects on CYPs or drug transporters. Note: severe diarrhoea, nausea and vomiting can occur within the first few weeks after initiating apremilast treatment. Patients should be instructed to contact their healthcare provider if they experience severe diarrhoea, nausea or vomiting as this could potentially alter the absorption of orally administered antiretroviral drugs.

Coadministration has not been studied. Aprepitant is mainly metabolized by CYP3A4 and to a lesser extent by CYPs 1A2 and 2C19. Lopinavir/ritonavir is a strong inhibitor of CYP3A4 and could potentially increase aprepitant concentrations. The European product label for aprepitant advises caution with CYP3A4 inhibitors, whereas the American product label advises to avoid concomitant use of aprepitant and moderate to strong CYP3A4 inhibitors. If coadministration is necessary, reduced doses of aprepitant may be required to minimize side effects. Aprepitant shows an initial inhibitory effect on CYP3A4 followed by a weak inducing effect from day 8 which is clinically insignificant by two weeks. Any transient change in lopinavir/ritonavir exposure is unlikely to be clinically significant.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Argatroban undergoes metabolism in the liver via hydroxylation and aromatization. In vitro studies indicate that CYP3A4 plays a role in argatroban metabolism, however, human drug-drug interactions studies suggest that metabolism via CYP3A4 is not a major elimination pathway in vivo. Erythromycin (a strong CYP3A4 inhibitor) had no effect on argatroban pharmacokinetics and pharmacodynamics and an interaction with lopinavir/ritonavir is unlikely.

Coadministration has not been studied. Aripiprazole is metabolized by CYP3A4 and CYP2D6. Lopinavir/ritonavir could potentially increase aripiprazole concentrations. Monitor adverse effects and decrease aripiprazole dosage if needed. The European SPC advises reducing the aripiprazole dose to approximately one-half of its prescribed dose when given with potent inhibitors of CYP3A4, such as HIV protease inhibitors. In addition, use with caution as both drugs have a possible risk of QTc prolongation on the CredibleMeds.org website. If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Data from clinical studies and population modelling suggest that coadministration of lopinavir/ritonavir and artesunate or artemether decreases exposure of dihydroartemisinin (the biologically active metabolite) by ~40-60%. Further studies are required to determine the clinical significance of this reduction and if dose modifications are required.

Coadministration has not been studied. Asciminib is metabolised by several pathways, including CYP3A4, UGT2B7 and UGT2B17. Lopinavir/ritonavir is metabolized by CYP3A and is a strong inhibitor of CYP3A4. Ritonavir induces UGTs. Coadministration of asciminib (40 mg single dose) with clarithromycin (a strong CYP3A4 inhibitor) increased asciminib AUC and Cmax by 36% and 19%, although no clinically significant effect on asciminib concentrations was observed when coadministered with itraconazole, which is also a strong CYP3A4 inhibitor. Lopinavir/ritonavir could possibly cause a less pronounced increase due to the inducing effect of ritonavir on UGTs. Increased asciminib exposure is unlikely to be significant for patients on asciminib doses of 40-80 mg daily. However, for patients on the higher dose of 200 mg twice daily, closely monitor for adverse reactions if coadministered with lopinavir/ritonavir. In addition, caution should be exercised as both lopinavir and asciminib have a risk of QT prolongation and/or TdP.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ascorbic acid is oxidised to dehydroascorbic acid where some is metabolised to oxalic acid and the inactive ascorbate-2-sulphate. Large doses are rapidly excreted in the urine when in excess of the requirements of the body. Lopinavir/ritonavir does not interfere with this metabolic pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with vitamin C when given alone or in multivitamins. Ascorbic acid is oxidised to dehydroascorbic acid where some is metabolised to oxalic acid and the inactive ascorbate-2-sulphate. Large doses are rapidly excreted in the urine when in excess of the requirements of the body. Lopinavir/ritonavir does not interfere with this metabolic pathway.

Coadministration has not been studied. Asenapine is metabolized by glucuronidation (UGT1A4) and oxidative metabolism (mainly CYP1A2, with minor contributions from CYP3A4 and CYP2D6). As lopinavir/ritonavir induces CYP1A2 and UGT1A4, lopinavir/ritonavir could potentially decrease asenapine exposure. Monitor the clinical effect and increase dosage if needed. Use with caution as both drugs have a possible risk of QTc prolongation on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Ashwagandha extracts had no effect on CYP enzymes in vitro.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Limited data suggest that asparaginase is likely to be eliminated by the reticuloendothelial system.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aspirin is rapidly deacetylated to salicylic acid and then further metabolized mainly by glucuronidation (by several UGT, major UGT1A6).

Coadministration of astemizole and lopinavir/ritonavir is contraindicated due to potential for serious and/or life threatening reactions such as cardiac arrhythmias. Furthermore, both drugs have a  risk of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; known risk for astemizole). Caution should be exercised if coadministered. ECG monitoring is recommended.

Coadministration of atazanavir (once daily) and lopinavir/ritonavir (twice daily) increased atazanavir Cmin (with no effect on AUC) and decreased lopinavir AUC. When used (very selected indications), the recommended dose is atazanavir 300 mg once daily plus lopinavir/ritonavir 400/100 mg twice daily. TDM of atazanavir and lopinavir should be considered. Use with caution as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; conditional risk for atazanavir). 

Coadministration of atazanavir (once daily) and lopinavir/ritonavir (twice daily) increased atazanavir Cmin (with no effect on AUC) and decreased lopinavir AUC. When used (very selected indications), the recommended dose is atazanavir 300 mg once daily plus lopinavir/ritonavir 400/100 mg twice daily. TDM of atazanavir and lopinavir should be considered. Use with caution as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; conditional risk for atazanavir). 

Atazanavir/cobicistat should not be administered concurrently with lopinavir co-formulated with ritonavir due to similar effects of cobicistat and ritonavir on CYP3A4. Furthermore, both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; conditional risk for atazanavir). 

Coadministration has not been studied. A dose adjustment of atenolol is unlikely to be required when coadministered as atenolol is eliminated by the kidney, both by glomerular filtration and active secretion via the renal transporters OCT2 and MATE1. The impact on the PR interval has not been evaluated for the coadministration of lopinavir/ritonavir and atenolol, however, no additive effect on the PR interval was noted for the coadministration of atazanavir and atenolol. Note, PR interval monitoring may be warranted in patients with underlying block or those with atrioventricular nodal blocking agents.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Atezolizumab is eliminated through catabolism. Lopinavir/ritonavir is mainly metabolized by CYP3A4.

Coadministration has not been studied. Atogepant is metabolized primarily by CYP3A4 and is a substrate of OATP. Concentrations of atogepant are expected to increase significantly due to strong inhibition of CYP3A4 and OATP by lopinavir/ritonavir. Atogepant AUC increased by 5.5-fold with itraconazole (a strong CYP3A4 inhibitor) and by 2.85-fold with single dose rifampicin (a strong OATP inhibitor). The European product label for atogepant recommends a dose reduction to 10 mg once daily with strong CYP3A4 and OATP inhibitors. For the treatment of episodic migraine, the American product label for atogepant recommends a dose reduction to 10 mg once daily with strong CYP3A4 inhibitors and recommends to avoid use with strong CYP3A4 inhibitors if treatment is for chronic migraine.

Coadministration has not been studied. Atomoxetine is metabolized by CYP2D6. Atomoxetine exposure could potentially increase, although to a limited extent, as ritonavir is a weak inhibitor of CYP2D6 when used as a pharmacokinetic booster. No a priori dosage adjustment is recommended. However, use with caution as both drugs have possible risks of QT prolongation and/or TdP on the CredibleMeds.org website. 

Coadministration of atorvastatin (20 mg once) and lopinavir/ritonavir (400/100 mg twice daily) had no significant effect on lopinavir (Cmax, AUC and Cmin decreased by 10%, 10% and 8%, respectively), but increased atorvastatin Cmax, AUC and Cmin by 4.7-fold, 5.9-fold and 2.3-fold, respectively. Coadministration is not recommended unless specifically required for patient management. Use the lowest possible dose of atorvastatin with careful monitoring (do not exceed a daily dose of 20 mg with careful safety monitoring.) or consider using other HMG-CoA reductase inhibitors such as pravastatin or fluvastatin in combination with lopinavir/ritonavir. (Note, American treatment guidelines recommend a maximum daily dose of 20 mg for atorvastatin.)

The AUCs of single dose atovaquone/proguanil (250/100 mg) were 74% and 38% lower, respectively, in HIV-infected individuals on stable antiretroviral treatment containing lopinavir/ritonavir (400/100 mg twice daily or 800/200 mg once daily) than in healthy volunteers. The clinical relevance of this interaction is unknown due to the lack of data on the minimal effective atovaquone plasma concentration in the setting of malaria prophylaxis. Consider taking atovaquone/proguanil with a high fat meal to increase its bioavailability and increase the dosage if required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely when atropine is used either systemically or as eye drops. Although metabolism of atropine is not fully elucidated, up to 50% is excreted unchanged via the kidneys. There is therefore little potential for clinically significant interactions with lopinavir/ritonavir via modulation of, or competition for metabolic pathways.

Coadministration has not been studied and is contraindicated. Avanafil is primarily metabolized by CYP3A4. Coadministration with ritonavir (600 mg twice daily) increased avanafil AUC by 13-fold. Similarly, a large increase in avanafil exposure is predicted in the presence of lopinavir/ritonavir.

Coadministration has not been studied and should be avoided. Avapritinib is predominantly mediated by CYP3A4 and to a minor extent by CYP2C9. Lopinavir/ritonavir is a strong inhibitor of CYP3A4 and could significantly increase avapritinib exposure. Based on drug interaction studies with other strong CYP3A4 inhibitors, avapritinib exposure is expected to increase by 600% after multiple doses.

Coadministration has not been studied. Avatrombopag is mainly metabolized by CYP2C9 and CYP3A4. Lopinavir/ritonavir is a strong inhibitor of CYP3A4 and is expected to increase concentrations of avatrombopag. Coadministration of avatrombopag and itraconazole (a strong CYP3A4 inhibitor) increased avatrombopag exposure by 37%. A similar effect may occur with lopinavir/ritonavir. No a priori dose adjustment is needed for avatrombopag but monitor platelet counts and adjust the avatrombopag dose as necessary as indicated in the avatrombopag product label.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Avelumab is primarily metabolized through catabolic pathways and drug-drug interactions are not expected.

Coadministration has not been studied. Axitinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2, CYP2C19 and UGT1A1. Lopinavir/ritonavir is a strong inhibitor of CYP3A4 and has some inducing effects on CYP1A2, CYP2C19 and UGT1A1. Given that CYP3A4 is the major pathway, lopinavir/ritonavir is expected to increase concentrations of axitinib. Increased axitinib exposure may increase the risk of exposure-related toxicity. Coadministration of ketoconazole (a strong CYP3A4 inhibitor) with axitinib increased axitinib AUC by 2-fold. A similar effect is expected with lopinavir/ritonavir. Use with caution. If coadministration is unavoidable, a 50% dose reduction of axitinib is recommended and monitor for toxicity.

Coadministration has not been studied. Ayahuasca preparations contain N,N-dimethyltryptamine (DMT, a psychedelic substance along with monoamine oxidase inhibitors (MAOI) which attenuates the breakdown of DMT. MAOI are substrate of MRP2 which is inhibited by lopinavir/ritonavir thereby potentially increasing DMT toxicity by slowing its breakdown. Given the narrow therapeutic index of DMT, caution is advised. Harma alkaloids found in ayahuasca preparations may cause weak/moderate inhibition of CYP3A4 which is unlikely to alter exposure of lopinavir/ritonavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Azacitidine undergoes spontaneous hydrolysis and deamination mediated by cytidine deaminase. Urinary excretion is the primary route of elimination of azacitidine and/or its metabolites. Following cellular uptake, azacitidine is sequentially phosphorylated via phosphokinases activities to azacitidine triphosphate which is able to incorporate into DNA and RNA. Lopinavir/ritonavir is metabolised by CYP3A4. Azacitidine does not inhibit or induce CYP enzymes.

Coadministration has not been studied. Azilsartan is metabolized mainly by CYP2C9. In vitro and in vivo data indicate that ritonavir is a weak inducer of CYP2C9. Lopinavir/ritonavir could potentially decrease azilsartan concentrations, however, the clinical relevance of this is unknown. No a priori dose adjustment is required.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Lopinavir/ritonavir is metabolized by CYP3A. Azithromycin is not expected to have a clinically relevant effect on drugs metabolised by CYP enzymes. Azithromycin is mainly eliminated via biliary excretion and animal data suggest this may occur via P-glycoprotein and MRP2. Lopinavir/ritonavir could potentially increase azithromycin exposure (inhibition of P-gp and MRP2), however no a priori dosage adjustment is recommended for azithromycin. However, caution should be exercised as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; known risk for azithromycin). If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Baricitinib is mainly eliminated renally through glomerular filtration and active secretion via OAT3, P-gp, BCRP and MATE2-K, with CYP3A4 metabolism representing less than 10% of its overall metabolism. Lopinavir/ritonavir is metabolized by CYP3A4 and is a strong inhibitor of CYP3A4. Baricitinib is not expected to have a clinically relevant effect on drugs metabolised by CYP enzymes. No effect on baricitinib is expected as it is mainly eliminated renally and CYP3A4 contributes to less than 10% of its overall metabolism. Coadministration with ketoconazole (a strong CYP3A4 inhibitor) had no significant impact on baricitinib exposure.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Basiliximab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body.

Coadministration with bazedoxifene alone or coformulated with conjugated estrogens as hormone replacement therapy (HRT) has not been studied. Bazedoxifene is glucuronidated by UGT1A1/8/10 and conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Coadministration could potentially decrease exposure of bazedoxifene and conjugated estrogens due to induction of CYP1A2 and glucuronidation. Monitor for signs of estrogen deficiency.

In vitro data indicate that beclometasone is a pro-drug which is hydrolysed via esterase enzymes to the highly active metabolite beclometasone -17-monopropionate. This active metabolite is subsequently converted to inactive metabolites via CYP3A4/5. Coadministration of ritonavir (100 mg twice daily) and inhaled beclomethasone diproprionate (160 mg twice daily) increased the AUC and Cmax of beclomethasone-17-monoproprionate by 108% and 67%, respectively. However, coadministration of a boosted PI (darunavir/ritonavir, 600/100 mg twice daily) decreased the AUC and Cmax of the active metabolite by 11% and 19%, respectively. No significant effect on adrenal function was seen with either ritonavir or darunavir/ritonavir. Although statistically significant, the 2-fold increase in AUC of the active metabolite seen with ritonavir is unlikely to be of clinical significance. Use the lowest possible corticosteroid dose with caution and monitor for corticosteroid side effects.

Coadministration of bedaquiline (400 mg single dose) and lopinavir/ritonavir (400/100 mg twice daily) to 16 HIV/TB-negative subjects increased bedaquiline AUC by 22% and had no effect on Cmax. Coadministration of bedaquiline (400 mg, once daily loading dose; 200 mg once daily maintenance dose for ~3 months) with lopinavir/ritonavir increased bedaquiline AUC by 62% but had no significant effect on the pharmacokinetics of the bedaquiline M2 metabolite. Bedaquiline and lopinavir have a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website. When bedaquiline is coadministered with other medicinal products that prolong the QTc interval, an additive or synergistic effect on QT prolongation cannot be excluded. Bedaquiline must be used with caution when co-administered with lopinavir/ritonavir and only if the benefit outweighs the risk. The combination of bedaquiline and moderate or strong CYP3A4 inhibitors used systemically for more than 14 consecutive days should be avoided. If coadministration is necessary, clinical monitoring including frequent electrocardiogram assessment and monitoring of transaminases is recommended. There are no clinical data on the safety and efficacy of bedaquiline when co-administered with antiretroviral agents.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Belatacept is a protein that undergoes non-CYP mediated metabolism in the liver.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Belimumab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body. Lopinavir/ritonavir is metabolized by CYP3A4.

Coadministration has not been studied. Bempedoic acid is glucuronidated by UGT2B7 and also converted to an active metabolite by aldo-keto reductase. Ritonavir induces UGT2B7 and could potentially reduce bempedoic acid concentrations. However, the clinical relevance is unknown given that several pathways are involved in the elimination of bempedoic acid. Bempedoic acid does not inhibit or induce CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benazepril is rapidly hydrolyzed to its active metabolite benazeprilat which is eliminated predominantly renally.

Coadministration has not been studied. Bendamustine is metabolised by multiple routes including hydrolysis (main), glutathione conjugation and hepatic metabolism via CYP1A2 (to form the metabolites M3 and M4). Lopinavir/ritonavir is metabolized by CYP3A4. Bendamustine does not inhibit or induce CYP enzymes. However, ritonavir induces CY1A2 and lopinavir/ritonavir has the potential to increase the formation of the metabolites but the clinical relevance is unknown as CYP1A2 plays a minor role in the overall metabolism. In addition, caution should be exercised as both lopinavir and bendamustine have a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bendroflumethiazide is mainly eliminated by hepatic metabolism (70%), although the exact pathway is not known. It is unlikely that CYP enzymes are involved in this process and no transporter interactions have been described. There is no evidence that bendroflumethiazide inhibits or induces CYP450 enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benserazide is hydrolysed to trihydroxybenzylhydrazine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Available information on the metabolism of benzatropine is limited but no clinically significant interactions are expected. Lopinavir/ritonavir is metabolised by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Benznidazole undergoes non-CYP mediated metabolism and partly CYP mediated metabolism. Renal elimination of unchanged benznidazole appears to be minimal and there is little potential for an interaction via competition for renal elimination pathways.

Bepridil and lopinavir should not be coadministered. Coadministration has not been studied, but may increase bepridil concentrations and has the potential to produce serious and/or life-threatening adverse events. Caution is warranted and concentration monitoring is recommended if coadministered. In addition, caution should be exercised as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; known risk for bepridil).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Beta-alanine is a non-essential amino acid and dietary supplements enter the same physiological processes as endogenous beta-alanine. Excess beta-alanine is excreted in the urine by the kidneys. Lopinavir/ritonavir is metabolised by CYP3A4. Beta-alanine is unlikely to affect CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betahistine is metabolized by monoamine oxidase. Betahistine does not induce or inhibit CYP450 enzymes.

Coadministration has not been studied. Betamethasone is metabolized by CYP3A4 and coadministration may therefore lead to elevated corticosteroid levels, Cushing’s syndrome and adrenal axis suppression. A case of Cushing’s syndrome and adrenal suppression in a patient on atazanavir/ritonavir and dexamethasone 0.1% eye drops and betamethasone 0.1% eye ointment has been reported. Betamethasone is a moderate inducer of CYP3A4. Chronic or high doses of betamethasone may decrease lopinavir/ritonavir plasma concentrations due to CYP3A4 induction with the possible loss of therapeutic effect and development of resistance. However, this risk is expected to be lower when using lower doses of betamethasone. Furthermore, the risk of Cushing’s syndrome is less likely to occur when using betamethasone at a low dose or for a short treatment duration as compared to higher doses and long treatment duration.

Coadministration has not been studied but no clinically relevant drug interactions are expected with the topical use of betamethasone (for example, ointment, cream, lotion, emollient, foam).

Coadministration has not been studied. Betrixaban is largely eliminated unchanged through biliary secretion via P-gp. Coadministration with a P-gp inhibitor (such as lopinavir/ritonavir) is expected to increase betrixaban exposure. The US product label for betrixaban recommends for patients receiving or starting a strong P-gp inhibitor to reduce betrixaban dose and use an initial dose of 80 mg followed by 40 mg once daily.  Furthermore, patients should be monitored closely and any signs or symptoms of blood loss should be evaluated promptly. Betrixaban has demonstrated an exposure dependent increase in QT interval therefore caution is required when coadministering with another drug that may prolong the QTc interval (betrixaban and lopinavir have a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website). Of note, coadministration of betrixaban might need to be reconsidered in patients with concomitant renal impairment (creatinine clearance <60 ml/ml) as renal impairment per se does increase betrixaban exposure. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant pharmacokinetic interaction is unlikely as bevacizumab is metabolized via proteolytic catabolism.

Coadministration has not been studied and should be avoided. Bexarotene is mainly metabolized by CYP3A4 and induces CYP3A4 (after repeated administration and especially at doses greater than 300 mg/m2/day). Coadministration could potentially increase bexarotene concentrations and thus increase the risk of side effects. In addition, bexarotene could potentially decrease lopinavir/ritonavir exposure and therefore coadministration should be avoided.

Coadministration has not been studied. Bicalutamide is metabolized by CYP3A4 and UGT1A9. Lopinavir/ritonavir is metabolized by CYP3A4. Bicalutamide is a weak inhibitor of CYP3A4 but is unlikely to have a clinically significant effect on lopinavir/ritonavir. Inhibition of CYP3A4 by lopinavir/ritonavir may increase bicalutamide concentrations. No a priori dose reduction is required but use with caution and monitoring of side effects is recommended. Note, androgen deprivation treatment may prolong the QT interval. Caution should be taken when using with antiretroviral drugs that can potentially prolong the QT interval such as lopinavir.

Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with lopinavir/ritonavir would be possible from a pharmacokinetic standpoint. Coadministration may increase bictegravir concentrations due to inhibition of CYP3A4 by lopinavir/ritonavir but this is unlikely to require dose modification. Coadministration of lopinavir/ritonavir and emtricitabine/tenofovir alafenamide had no significant effect on lopinavir and increased exposure of tenofovir alafenamide. The recommended dose of 10 mg tenofovir alafenamide with P-gp inhibitors is not possible with Biktarvy which is only available as a fixed dose combination containing 25 mg tenofovir alafenamide, but it should be noted that tenofovir alafenamide has been associated with a large clinical safety profile.

Coadministration has not been studied. Bilastine is mainly excreted unchanged and is a substrate of P-gp and OATP1A2. Lopinavir/ritonavir is metabolised by CYP3A4. Bilastine is unlikely to affect CYP3A4. However, ritonavir is a strong P-gp inhibitor and a weak OATP1B1 inhibitor and is expected to increase bilastine concentrations. No a priori dose modification is recommended but close monitoring for signs and symptoms of increased bilastine exposure is recommended. Coadministration of bilastine and P-gp inhibitors should be avoided in subjects with moderate or severe renal impairment.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bimekizumab is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Lopinavir/ritonavir is metabolized by CYP3A4.

Coadministration has not been studied. Binimetinib is primarily metabolised by UGT1A1 and the active metabolite M3 is metabolised by CYP1A2 and CYP2C19. Lopinavir/ritonavir is mainly metabolized by CYP3A4. Binimetinib is unlikely to affect CYP3A4. However, ritonavir induces glucuronidation, CYP1A2 and CYP2C19 and lopinavir/ritonavir has the potential to decrease exposure of binimetinib. Use with caution.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following absorption, vitamin B7 is stored in the liver, kidney and pancreas.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Following absorption, vitamin B7 is stored in the liver, kidney and pancreas.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although limited human data suggest biperiden undergoes hydroxylation in the liver, there are no known or documented interactions with other drugs that have an effect on metabolism or transport.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bismuth subsalicylate is largely hydrolysed in the stomach to form salicylic acid, which is rapidly absorbed, and insoluble bismuth salts, which are excreted unchanged in faeces. Lopinavir/ritonavir is metabolised by CYP3A4. Bismuth subsalicylate is unlikely to affect CYP3A4.

Coadministration has not been studied. Bisoprolol is partly metabolized by CYP3A4 and CYP2D6 and partly eliminated unchanged in the urine. Coadministration could potentially increase bisoprolol concentrations, although to a moderate extent. Pharmacokinetic studies between lopinavir/ritonavir and drugs that prolong the PR interval, including beta blockers, have not been performed. An additive effect of lopinavir/ritonavir and these drugs cannot be excluded. Note, PR interval monitoring may be warranted in patients with underlying block or those with atrioventricular nodal blocking agents.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. No effect on lopinavir/ritonavir is expected as black cohosh had no significant effect on the pharmacokinetics of midazolam (a CYP3A4 substrate) or digoxin (a P-gp substrate).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. An indirect effect of blinatumomab on CYPs may occur due to transient release of cytokines during the first days of therapy which can inhibit CYP450 metabolism, however, this is unlikely to be clinically relevant. The metabolic pathway of blinatumomab has not been characterised. Like other protein therapeutics, blinatumomab is expected to be degraded into small peptides and amino acids via catabolic pathways.

Coadministration has not been studied. Bortezomib is mainly metabolized by CYP3A4 and 2C19 and to a lesser extent by CYPs 1A2, 2D6 and 2C9. Lopinavir/ritonavir could potentially increase bortezomib concentrations. Monitor for bortezomib-related side effects. The US Prescribing Information suggests considering a dose reduction of bortezomib when given with strong CYP3A4 inhibitors, such as ritonavir. Caution is advised when prescribing bortezomib and lopinavir/ritonavir as both drugs have a possible risk or QT prolongation and/or TdP on the CredibleMeds.org website. If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Caution should be exercised in administering lopinavir/ritonavir with bosentan. Coadministration with lopinavir/ritonavir increased bosentan trough concentrations by ~48-fold and ~5-fold on days 4 and 10, respectively. Lopinavir/ritonavir concentrations may decrease due to CYP3A4 induction by bosentan. When coadministered patients should be closely observed for bosentan toxicity, especially during the first week of co-administration. The US Prescribing Information suggests for patients who have been receiving lopinavir/ritonavir for at least 10 days, to start bosentan at 62.5 mg once daily or every other day based upon individual tolerability. In patients on bosentan, it suggests to discontinue bosentan at least 36 hours prior to initiation of lopinavir/ritonavir and after at least 10 days of lopinavir/ritonavir, to resume bosentan at 62.5 mg once daily or every other day based upon individual tolerability.

Coadministration has not been studied but should be avoided. Bosutinib is metabolized by CYP3A4. Ketoconazole (a strong CYP3A4 inhibitor) increased bosutinib AUC by 8.6-fold. A similar effect may occur with lopinavir/ritonavir. Use an alternative antiretroviral drug with no inhibitory or inducing effects.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Branched chain amino acids (BCAAs) mainly undergo intracellular catabolism in skeletal muscle. Excess BCAAs and BCAA-derived metabolic products are excreted in the urine by the kidneys. Lopinavir/ritonavir is metabolised by CYP3A4. BCAAs are unlikely to affect CYP3A4.

Coadministration has not been studied but should be used with caution. Brentuximab vedotin is an antibody-drug conjugate comprising a monoclonal antibody and monomethyl auristatin E (MMAE), a potent chemotherapeutic agent. The monoclonal antibody undergoes elimination via intracellular catabolism and does not interact with lopinavir/ritonavir. However, MMAE is a substrate of CYP3A4 and P-gp, therefore lopinavir/ritonavir may increase concentrations of MMAE and the incidence of neutropenia. Coadministration of brentuximab vedotin and ketoconazole (a strong inhibitor of CYP3A4 and P-gp) increased MMAE AUC by 34%. Patients receiving lopinavir/ritonavir concomitantly with brentuximab vedotin should be closely monitored for adverse reactions of brentuximab vedotin. If neutropenia develops, refer to the dosing recommendations for neutropenia in the product label for brentuximab vedotin.

Coadministration has not been studied. Brexpiprazole is predominantly metabolised by CYP3A4 and CYP2D6. Lopinavir/ritonavir is metabolized by CYP3A4 and is a strong inhibitor of CYP3A4. Ketoconazole (a strong CYP3A4 inhibitor) increase brexpiprazole AUC by 97% and similar effect may occur with lopinavir/ritonavir. Product labels for brexpiprazole advise a dose reduction of 50% with strong CYP3A4 inhibitors. A dosing modification to a quarter of the recommended dose is required for known CYP2D6 poor metabolisers while taking strong inhibitors. Monitor for toxicity, such as confusion, restlessness and sedation.

Coadministration has not been studied. Brigatinib is metabolised by CYP2C8 and CYP3A4. Lopinavir/ritonavir is a strong inhibitor of CYP3A4 and is expected to increase brigatinib concentrations. Coadministration of brigatinib (90 mg single dose) and itraconazole, a strong CYP3A4 inhibitor (200 mg twice daily) increased brigatinib exposure by 101%. A similar effect is expected with lopinavir/ritonavir and coadministration is not recommended. If coadministration is necessary, reduce the dose of brigatinib by 50% and monitor for toxicity.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Brimonidine is metabolized mainly by aldehyde oxidase.

Coadministration has not been studied. Brincidofovir is a prodrug converted to cidofovir which is eliminated renally via glomerular filtration and active renal secretion by OAT1 and OAT3. Lopinavir/ritonavir does not interfere with this pathway. However, brincidofovir is a substrate of OATP1B1 and concentrations may increase due to inhibition of OATP1B1 by lopinavir/ritonavir. If concomitant use with brincidofovir is necessary, increase the monitoring for adverse reactions associated with brincidofovir (i.e. elevations in transaminases and bilirubin, diarrhoea, or other gastro-intestinal adverse events) and postpone the dosing of lopinavir/ritonavir for at least 3 hours after brincidofovir administration.

Coadministration has not been studied. Brinzolamide is mainly metabolised by CYP3A4, and to a lesser extent by CYPs 2A6, 2C8 and 2C9. Lopinavir/ritonavir is metabolised by CYP3A4. Brinzolamide does not inhibit or induce CYP3A4. However, lopinavir/ritonavir is a strong CYP3A4 inhibitor and may increase brinzolamide concentrations. Caution is advised, and a dose reduction could be considered at higher doses. Monitor for increased side effects such as blurred vision or eye irritation and consider intraocular pressure checks during the first week of coadministration.

Coadministration has not been studied. Bromazepam undergoes oxidative biotransformation. Drug-drug interaction studies indicate that CYP3A4 plays a minor role in bromazepam metabolism, but other cytochromes such as CYP2D6 or CYP1A2 may play a role. Bromazepam does not inhibit CYP3A4. Lopinavir/ritonavir could potentially increase bromazepam concentrations although to a moderate extent. Coadministration with itraconazole (a strong CYP3A4 inhibitor) increased bromazepam AUC by ~9%. A similar effect may occur with lopinavir/ritonavir. No a priori dosage adjustment is required.

Coadministration has not been studied. Bromocriptine is metabolised by CYP3A4. Lopinavir/ritonavir is metabolised by CYP3A4. Bromocriptine is unlikely to affect CYP3A4 at clinically relevant concentrations. However, lopinavir/ritonavir is a strong inhibitor of CYP3A4 and may increase bromocriptine concentrations. Erythromycin (a strong CYP3A4 inhibitor) increased bromocriptine AUC by 3.7-fold and a similar effect may occur with lopinavir/ritonavir. Use with caution. A decrease in bromocriptine dose may be needed.

Concomitant use of lopinavir/ritonavir and glucocorticoids metabolised by CYP3A4 is not recommended unless the potential benefit of treatment outweighs the risk of systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression. Systemic corticosteroid effects have been reported in patients receiving ritonavir and fluticasone; this could also occur with other corticosteroids metabolised via the P450 3A pathway e.g. budesonide. A dose reduction of the glucocorticoid should be considered with close monitoring of local and systemic effects or a switch to a glucocorticoid, which is not a substrate for CYP3A4 (e.g. beclometasone). Moreover, in case of withdrawal of glucocorticoids progressive dose reduction may have to be performed over a longer period.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bumetanide is hepatically metabolized and approximately 50-80% of bumetanide is excreted in the urine by OAT1 and OAT3, mainly as unchanged drug (~50%). Lopinavir/ritonavir is metabolized by CYP3A4 and is unlikely to inhibit OATs at clinically relevant concentrations.

Coadministration has not been studied. Bupivacaine is predominantly metabolized by CYP3A4. CYP3A4 inhibitors such as lopinavir/ritonavir may increase levels of bupivacaine. A clinical study with bupivacaine and itraconazole, a CYP3A4 inhibitor, reported a 20-25% increase in steady state concentration of bupivacaine when administered with itraconazole, compared to placebo.

Coadministration had no significant effect on the pharmacokinetics of buprenorphine and did not result in opiate withdrawal symptoms. When compared to control data, buprenorphine increased lopinavir AUC by 15%, but had no effect on Cmax or Cmin. Lopinavir/ritonavir can be coadministered with buprenorphine with no dose adjustment.

Coadministration decreased bupropion AUC and Cmax by ~57%; active metabolite AUC and Cmax decreased by 31% and 50%, respectively (data from 12 HIV- subjects). Single dose of bupropion had no effect on the pharmacokinetics of lopinavir and ritonavir. If the coadministration is judged unavoidable, this should be done under close clinical monitoring for bupropion efficacy, without exceeding the recommended bupropion dosage, despite the observed induction.

Coadministration has not been studied. Busulfan is metabolised through conjugation with glutathione (spontaneous and GST-mediated) and then by hepatic oxidation (likely CYP3A4-mediated). Lopinavir/ritonavir is metabolised by CYP3A4. Busulfan is unlikely to affect CYP3A4. However, lopinavir/ritonavir is a strong inhibitor of CYP3A4 and may increase busulfan concentrations. Itraconazole (a strong CYP3A4 inhibitor) decreased busulfan clearance by approximately 20%. A similar effect may occur with lopinavir/ritonavir which may increase the risk and severity of myelosuppression. Patients should be monitored for signs of toxicity.

Coadministration has not been studied and should be used with caution. Cabazitaxel is metabolized by CYP3A4. Coadministration with ketoconazole (a strong CYP3A4 inhibitor) increased cabazitaxel exposure by 25% and a similar effect is expected with lopinavir/ritonavir. Thus, coadministration should be avoided but if coadministration is required, consider a dose reduction of cabazitaxel of up to 25% and monitor for cabazitaxel toxicity.

Coadministration has not been studied. Cabergoline is extensively metabolized by the liver, predominantly via hydrolysis (non-CYP mediated metabolism), and is a substrate of P-gp. Cabergoline exposure increased by 2.6- to 4-fold in the presence of the strong P-gp inhibitors itraconazole or clarithromycin. Similarly, coadministration with lopinavir/ritonavir is expected to increase cabergoline exposure. Consider a reduction in cabergoline dose if the patient presents with adverse drug effects. No effect on lopinavir/ritonavir is expected as cabergoline does not inhibit or induce drug metabolizing enzymes. 

Coadministration has not been studied but a clinically significant interaction is unlikely when cabergoline is administered as a single dose to suppress lactation. Cabergoline is extensively metabolized by the liver, predominantly via hydrolysis (non-CYP mediated metabolism), and is a substrate of P-gp. Cabergoline exposure was shown to increased 2.6- to 4-fold in the presence of the strong P-gp inhibitors itraconazole or clarithromycin. Although lopinavir/ritonavir inhibits P-gp, no dose adjustment of cabergoline is required when cabergoline is administered as a single dose to suppress lactation. No effect on lopinavir/ritonavir is expected as cabergoline does not inhibit or induce drug metabolizing enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Induction of UGTs by ritonavir used to boost lopinavir is unlikely to cause a clinically relevant decrease in cabotegravir exposure based on drug-drug interaction studies with rifabutin, another moderate inducer. Note, cabotegravir used as PrEP is not expected to be coadministered with antiretrovirals except in the case of breakthrough infection when an antiretroviral treatment should be initiated. Residual concentrations of cabotegravir may remain in the systemic circulation for prolonged periods (up to 12 months or longer) but are not expected to affect the exposure of antiretroviral drugs initiated after discontinuation of Apretude.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent UGT1A9. Induction of UGTs by ritonavir used to boost lopinavir is unlikely to cause a clinically relevant decrease in cabotegravir exposure based on drug-drug interaction studies with rifabutin, another moderate inducer. Cabotegravir is not expected to alter concentrations of other antiretroviral products. 

Cabenuva (cabotegravir LA, rilpivirine LA) is indicated for use as a complete regimen for the treatment of HIV-1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with lopinavir/ritonavir would be possible from a pharmacokinetic standpoint. Cabotegravir is mainly metabolized by UGT1A1 and to a lesser extent by UGT1A9. Induction of UGTs by ritonavir used to boost lopinavir is unlikely to cause a clinically relevant decrease of cabotegravir exposure based on drug-drug interaction studies with rifabutin, another moderate inducer. Coadministration of oral rilpivirine (150 mg once daily) and lopinavir/ritonavir (400/100 mg twice daily) increased rilpivirine Cmax, AUC and Cmin by 29%, 52% and 74%, respectively. Lopinavir Cmax, AUC and Cmin decreased by 4%, 1% and 11%, respectively. [Note: this interaction study has been performed with a dose higher than the licensed dose for rilpivirine assessing the maximal effect on the co-administered drug]. No dose adjustment of rilpivirine is required. Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses, but equivalent rilpivirine concentrations are unlikely to occur with lopinavir/ritonavir. However, the product label for rilpivirine indicates that rilpivirine should be used with caution in combination with drugs with a risk of QT interval prolongation. Lopinavir has a possible risk of QTc prolongation and/or TdP on the CredibleMeds.org website. Residual concentrations of cabotegravir and rilpivirine may remain in the systemic circulation of patients for a prolonged period after discontinuation of intramuscular cabotegravir/rilpivirine but are not expected to affect exposure of antiretroviral drugs.

Coadministration has not been studied but should be used with caution. Cabozantinib is metabolized by CYP3A4. Ketoconazole (a strong CYP3A4 inhibitor) increased cabozantinib AUC by 38%. A similar effect may occur with lopinavir/ritonavir. Avoid concomitant use with strong inhibitors if possible. If a strong CYP3A4 inhibitor must be used, reduce the cabozantinib daily dose by 20 mg. Resume the dose that was used prior to initiating the CYP3A4 inhibitor 2-3 days after discontinuation of the strong inhibitor. In addition, caution should be exercised as both lopinavir and cabozantinib have a risk of QT prolongation and/or TdP on the CredibleMeds.org website. If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Caffeine is mainly metabolised by CYP1A2. Lopinavir/ritonavir is metabolised by CYP3A4. Caffeine is unlikely to affect CYP3A4. In vivo data indicate that ritonavir induces CYP1A2 and could potentially decrease caffeine concentrations. However, no a priori dose adjustment is required.

Coadministration has not been studied. Caffeine is mainly metabolized by CYP1A2. In vivo data indicate that lopinavir/ritonavir induces CYP1A2 and therefore boosted protease inhibitors could potentially decrease caffeine concentrations. However, no a priori dose adjustment is required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Calcitonin is primarily metabolized via proteolysis in the kidney. Lopinavir/ritonavir does not interfere with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely.

Coadministration has not been studied. Canagliflozin is primarily metabolised by UGT1A9 and UGT2B4. Lopinavir/ritonavir could lead to reduced exposure to canagliflozin as a result of UGT enzyme induction by ritonavir as rifampicin (a nonselective inducer of several UGT enzymes, including UGT1A9, UGT2B4) decreased canagliflozin AUC by 51% which may result in reduced efficacy. If coadministration is deemed necessary, increasing canagliflozin to 300 mg once daily may be considered if patients are currently tolerating canagliflozin 100 mg once daily, have an eGFR ≥60 mL/min/1.73m2 or CrCl ≥60 mL/min, and require additional glycaemic control. Other glucose-lowering therapies should be considered for patients with an eGFR 45 mL/min/1.73m2 to <60 mL/min/1.73m2 or CrCl 45 mL/min to <60 mL/min taking canagliflozin 100 mg who are receiving concurrent therapy with a UGT enzyme inducer and who require additional glycaemic control.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Canakinumab is an IL-1 beta monoclonal antibody and is eliminated via intracellular catabolism. Lopinavir/ritonavir is metabolized by CYP3A4. Patients requiring treatment with anakinra may have elevated levels of cytokines (e.g., TNF-alpha, IL-1, IL-6, IL-10, IFN) which have been shown to suppress expression/activity of CYP3A4, CYP2C19, CYP2C9 and CYP1A2. Canakinumab, per se, has no inhibitory or inducing effects on cytochromes. Canakinumab will normalize cytochrome activity (via inhibition of IL-1) but no significant effect on lopinavir/ritonavir is expected and no a priori dose adjustment is required.

Coadministration has not been studied. Cannabidiol is mainly metabolized by CYP3A4 and CYP2C19. Coadministration with lopinavir/ritonavir may increase cannabidiol concentrations due to strong inhibition of CYP3A4 and decrease cannabidiol concentrations due to induction of CYP2C19. The net effect of these interactions is unknown. Monitor effect and occurrence of side effects and adjust cannabidiol dosage accordingly.

Coadministration has not been studied. Tetrahydrocannabinol (THC, the psychoactive component of cannabis) is metabolized mainly by CYP2C9 and to a lesser extent by CYP3A4. In vivo data indicate that ritonavir is a weak inducer of CYP2C9 and a strong inhibitor of CYP3A4. The net clinical effect of this interaction is difficult to predict as lopinavir/ritonavir could potentially decrease THC exposure (induction of CYP2C9) or increase THC exposure (inhibition of CYP3A4).

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Capecitabine is activated by sequential enzyme reactions to fluorouracil. Lopinavir/ritonavir does not interfere with this metabolic pathway. However, caution is advised when prescribing capecitabine and lopinavir/ritonavir as both drugs have a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Capmatinib is primarily metabolized by CYP3A4. Lopinavir/ritonavir is metabolized by CYP3A and is a strong inhibitor of CYP3A4. Coadministration of capmatinib (400 mg single dose) and itraconazole, a strong CYP3A4 inhibitor, (200 mg once daily), increased capmatinib exposure by 42% with no change to Cmax. A similar effect is expected with lopinavir/ritonavir. Given the modest increase in capmatinib exposure and its toxicity profile, no a priori dose adjustment of capmatinib is necessary, however, monitor as toxicity of capmatinib may be increased. If treatment-toxicities occur, a dose reduction should be considered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Capreomycin is predominantly excreted via the kidneys as unchanged drug.

Lopinavir/ritonavir should not be administered once-daily in combination with carbamazepine. Coadministration may result in a marked decrease in concentrations of lopinavir/ritonavir and increased concentrations of carbamazepine. Monitor carbamazepine concentrations. An increase of lopinavir/ritonavir dosage may be envisaged, but has not been evaluated.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carbidopa is partly metabolized and partly eliminated unchanged (30% of the total urinary excretion).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carbocisteine is metabolized in the liver via acetylation, decarboxylation and sulfoxidation with up to 60% excreted unchanged in the urine. The likelihood of a clinically significant drug interaction is low and no studies have been performed. Lopinavir/ritonavir is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carboplatin is excreted primarily by renal glomerular filtration and therefore there is little potential for a pharmacokinetic interaction.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Carfilzomib is rapidly metabolized, mainly by peptidase cleavage and epoxide hydrolysis with CYP-mediated metabolism representing a minor pathway. Lopinavir/ritonavir is metabolized by CYP3A4 and is a strong inhibitor of CYP3A4. Carfilzomib is not expected to have a clinically relevant effect on drugs metabolised by CYPs and is unlikely to be affected by inhibitors and inducers of CYPs and P-gp.

Coadministration has not been studied and is not recommended. Metabolism of cariprazine and its major active metabolites is mediated mainly by CYP3A4 with a minor contribution from CYP2D6. Lopinavir/ritonavir is metabolised by CYP3A4. Cariprazine is unlikely to affect CYP3A4. However, lopinavir/ritonavir is a strong CYP3A4 inhibitor and a weak CYP2D6 inhibitor and is expected to increase cariprazine concentrations. Cariprazine and its metabolites have very long elimination half-lives and changes in dose may not be fully reflected in plasma for several weeks. The European product label for cariprazine contraindicates coadministration with strong CYP3A4 inhibitors, whereas the American product label advises dose modification if a strong CYP3A4 inhibitor is initiated while on a stable dose of cariprazine. Refer to the cariprazine product labels for more information.

Coadministration has not been studied. Carvedilol undergoes glucuronidation via UGTs 1A1, 2B4 and 2B7, and metabolism via CYP2D6 and to a lesser extent CYPs 2C9 and 1A2. The net effect on carvedilol concentrations is difficult to predict but likely to be moderate in magnitude. Pharmacokinetic studies between lopinavir/ritonavir and drugs that prolong the PR interval (including beta blockers) have not been performed. An additive effect of lopinavir and these drugs cannot be excluded. Note, PR interval monitoring may be warranted in patients with underlying block or those with atrioventricular nodal blocking agents.

Coadministration has not been studied. Cat’s claw is a strong inhibitor of CYP3A4 in vitro but has also been shown to induce CYP3A4 activity in vitro. Increased concentrations of atazanavir, saquinavir and ritonavir were reported in a patient receiving Cat’s claw. Similar increases would be expected for other CYP3A4 substrates, such as lopinavir. Coadministration should be avoided.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cedazuridine is eliminated renally and converted to its epimer (which is then renally excreted). Lopinavir/ritonavir is metabolised by CYP3A4. Cedazuridine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefalexin is predominantly eliminated unchanged via the kidneys.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefazolin is predominantly eliminated unchanged via the kidneys.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Approximately 50% of the absorbed dose is excreted unchanged in the urine; there is no evidence of metabolism of cefixime in vivo. In vitro studies have shown that cefixime does not inhibit/induce major cytochrome P450 metabolic enzymes, and would not be expected to cause clinically significant interactions with other drugs, which are metabolized by CYP450 enzymes.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefotaxime is predominantly eliminated unchanged via the kidneys.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceftazidime is predominantly eliminated unchanged via renal glomerular filtration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ceftriaxone is eliminated mainly as unchanged drug; approximately 60% of the dose being excreted in the urine, almost exclusively by glomerular filtration, and the remainder via the biliary and intestinal tracts.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cefuroxime is not metabolised and is excreted predominantly by renal glomerular filtration, with no significant active renal tubular secretion. Lopinavir/ritonavir is metabolised by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Celecoxib is primarily metabolized by CYP2C9 and in vivo data indicate that lopinavir/ritonavir is a weak inducer of CYP2C9. A dose adjustment is unlikely to be required for celecoxib when coadministered with lopinavir/ritonavir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cemiplimab is primarily metabolised through catabolic pathways and drug-drug interactions are not expected. Lopinavir/ritonavir is metabolized by CYP3A4.

Coadministration has not been studied and is not recommended. Cenobamate is primarily glucuronidated by UGT2B7 and to a lesser extent by UGT2B4. CYP3A4 contributes to cenobamate metabolism but to a minor extent. Cenobamate is a dose-dependent inducer of CYP3A4 and was shown to reduce exposure of midazolam (a CYP3A4 substrate) by 72% at a dose of 200 mg daily and by 27% at a dose of 100 mg daily. Cenobamate is dose-titrated until the 200 mg maintenance dose is reached. Cenobamate at a daily dose of 200 mg or greater may significantly decrease lopinavir/ritonavir plasma concentrations due to CYP3A4 induction with the possible loss of therapeutic effect and development of resistance.

Coadministration has not been studied. Ceritinib is metabolized by CYP3A4. Lopinavir/ritonavir is a strong inhibitor of CYP3A4. Coadministration of ceritinib (450 mg single dose) with ketoconazole, a strong CYP3A/P-gp inhibitor (200 mg twice daily for 14 days) increased ceritinib AUC and Cmax by 2.9-fold and 1.2-fold. A similar effect is expected with lopinavir/ritonavir and therefore coadministration is not recommended. However, if coadministration is necessary, consider reducing ceritinib dose by 33% (dose rounded to the nearest multiple of the 150 mg dosage strength) and monitor for toxicity. In addition, caution should be exercised as both lopinavir and ceritinib have a risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Certolizumab pegol is an antibody Fab’ fragment conjugated with polyethylene glycol (PEG). The Fab’ fragment is expected to be degraded to peptides and amino acids by proteolysis; the PEG moiety is mainly excreted in urine without further metabolism. Lopinavir/ritonavir is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cetuximab is a monoclonal IgG antibody. Elimination is similar to endogenous IgG and occurs primarily via proteolytic catabolism throughout the body.

Coadministration has not been studied. In vitro studies have shown that chloramphenicol can inhibit metabolism mediated by CYP3A4. Coadministration of chloramphenicol may potentially increase levels of lopinavir/ritonavir via this mechanism, increasing the risk of adverse events. The clinical significance of this interaction is unknown Ocular use: Although chloramphenicol is systemically absorbed when used topically in the eye, the concentrations used are unlikely to cause a clinically significant interaction.

Coadministration with a chlormadinone-containing combined oral contraceptive (COC) has not been studied. Chlormadinone undergoes extensive hepatic metabolism by hydroxylation (likely CYP mediated). Coadministration is predicted to increase exposure of chlormadinone. When used in a combined pill, the estrogen component is reduced. Given the lack of clinical data on the contraceptive efficacy, caution is recommended and additional contraceptives measures should be used.

Coadministration has not been studied. Lopinavir/ritonavir is metabolised by CYP3A and inhibits CYP3A. Chloroquine is metabolised by CYPs 2C8, 3A4 and 2D6, and is also eliminated unchanged via the kidney (50%). No effect on lopinavir/ritonavir is expected, but inhibition of CYP3A by lopinavir/ritonavir may increase chloroquine concentrations (although to a moderate extent due to the multiple elimination pathways), thereby increasing the risk of QT prolongation as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (known risk for chloroquine; possible risk for lopinavir). Due to the very long half-life, the risk of QT prolongation may persist even after discontinuation of chloroquine. No dosage adjustment is recommended for chloroquine but ECG monitoring is advised.

Coadministration has not been studied. Chlorphenamine is predominantly metabolized in the liver via CYP2D6. Lopinavir/ritonavir could potentially increase chlorphenamine exposure although to a moderate extent as ritonavir is a weak inhibitor of CYP2D6. No a priori dosage adjustment is required.

Coadministration has not been studied. Chlorpromazine is metabolized mainly by CYP2D6, but also by CYP1A2. Lopinavir/ritonavir could potentially increase chlorpromazine exposure although to a moderate extent. In addition, caution should be exercised as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; known risk for chlorpromazine). If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Coadministration has not been studied. Ciclesonide can be administered with lopinavir/ritonavir without dose adjustment, but with close monitoring. There is a risk of steroid side effects occurring, particularly if a high dose is used, or in case of prolonged administration, or if used with another medicine containing corticosteroids. These side effects are also more likely during periods of physiological stress. Ciclesonide is a pro-drug activated by esterases in the lungs to des-ciclesonide which then undergoes CYP3A4-mediated metabolism. Coadministration of the strong CYP3A4 inhibitor ketoconazole (400 mg daily for 7 days) with orally inhaled ciclesonide (320 µg once daily) did not alter ciclesonide but resulted in a 3.5-fold increase in the AUC and a 2-fold increase in the Cmax of des-ciclesonide. Ciclesonide is mainly absorbed by the lungs, has a high protein binding and a high clearance resulting in a lower potential to cause systemic effects compared to some other inhaled corticosteroids. Hence, any interaction with lopinavir/ritonavir would not require any dosage/therapy adjustments, particularly if ciclesonide is administered at lower or medium clinical doses, but close monitoring for Cushing’s syndrome signs is required when using a higher dose or with prolonged administration. 

Coadministration may increase plasma concentrations of ciclosporin. More frequent therapeutic concentration monitoring is recommended until plasma levels have been stabilised.

Lopinavir/ritonavir can be coadministered with acid reducing agents with no dose adjustment. No reduction in lopinavir or ritonavir trough concentrations were observed over 48 weeks in HIV+ subjects receiving lopinavir/ritonavir with an acid reducing agent (antacids, proton pump inhibitors or H2 receptor antagonists).

Coadministration has not been studied. Cinacalcet is metabolized by multiple CYP enzymes, mainly CYP3A4, CYP2D6 and CYP1A2. Lopinavir/ritonavir is mainly metabolized by CYP3A4. Cinacalcet does not inhibit or induce CYP3A4. However, concentrations of cinacalcet may increase due to inhibition of CYP3A4 by lopinavir/ritonavir. Use with caution and a dose adjustment of cinacalcet may be required. Monitoring of iPTH serum phosphorus and serum calcium is recommended when starting or discontinuing a strong CYP3A4 inhibitor. Note, decreases in serum calcium can prolong the QT interval. Caution should be taken when using with antiretroviral drugs that can potentially prolong the QT interval such as lopinavir.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Ciprofloxacin is primarily eliminated unchanged by the kidneys by glomerular filtration and tubular secretion via OAT3. It is also metabolized and partially cleared through the bile and intestine. Lopinavir/ritonavir is unlikely to inhibit OATs at clinically relevant concentrations. However, caution should be exercised as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; known risk for ciprofloxacin). If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Coadministration of cisapride and lopinavir/ritonavir is contraindicated due to potential for serious and/or life threatening reactions such as cardiac arrhythmias. Both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; known risk for cisapride).

Coadministration has not been studied. Cisplatin is eliminated renally via OCT2 and MATE1 and in vitro data indicate that ritonavir is a moderate inhibitor of MATE1. Lopinavir/ritonavir could potentially slow down cisplatin renal elimination and thus increase the risk of nephrotoxicity. Close monitoring of renal function is recommended.

Coadministration has not been studied. Citalopram is metabolized by CYPs 2C19 (38%), 2D6 (31%) and 3A4 (31%). Lopinavir/ritonavir could potentially increase citalopram concentrations although to a moderate extent and no a priori dosage adjustment is recommended. In addition, caution should be exercised as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; known risk for citalopram). If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Particular caution must be used when prescribing lopinavir/ritonavir and medicinal products known to induce QT interval prolongation such as clarithromycin. Coadministration may increase clarithromycin concentrations. Dose reduction of clarithromycin required in patients with impaired renal function. In addition, caution should be exercised as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; known risk for clarithromycin). If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Coadministration has not been studied. Clobazam is metabolised by CYP3A4 (major) and CYP2B6 and CYP2C19 (minor) to the active metabolite N-desmethylclobazam, which is metabolised by CYP2C19. CYP3A4 inhibition by lopinavir/ritonavir may increase clobazam exposure and prolong the duration of its effect, whereas induction of CYP2C19 by lopinavir/ritonavir may decrease N-desmethylclobazam. The net effect of these interactions is unknown. Monitor for side effects and clinical effect. Clobazam is unlikely to significantly impact lopinavir/ritonavir.

Coadministration has not been studied. Clobetasol is a substrate of CYP3A4 and exposure may increase due to inhibition of CYP3A4 by lopinavir/ritonavir. Topical clobetasol can be used with caution. Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients. If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Clofazimine is largely excreted unchanged in the faeces, both as unabsorbed drug and via biliary excretion. Although both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (conditional risk for clofazimine; possible risk for lopinavir/ritonavir), the risk of QT interval prolongation is considered to be low as no significant pharmacokinetic interaction is expected.

Coadministration has not been studied. In vitro studies have suggested that transformation of clomifene to its active metabolite is likely to be mediated via CYP2D6. Lopinavir/ritonavir might increase clomifene exposure, although to a moderate extent, via CYP2D6 inhibition. No a priori dosage adjustment is recommended.

Coadministration has not been studied. Clomipramine is metabolized by CYPs 3A4, 1A2 and 2C19 to desmethylclomipramine, an active metabolite which has a higher activity than the parent drug. In addition, clomipramine and desmethylclomipramine are metabolized by CYP2D6. Coadministration could potentially increase clomipramine concentrations. Monitor adverse effects. Note, both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; conditional risk for clomipramine). Caution is advised as the product label for clomipramine advises to avoid coadministration with drugs that can prolong the QT interval.

Coadministration of clopidogrel and boosted regimens has been evaluated in clinical studies. Clopidogrel is a prodrug and is converted to its active metabolite via CYPs 3A4, 2B6, 2C19 and 1A2. In HIV-positive subjects, the presence of a pharmacoenhancer (ritonavir n=8; cobicistat n=1) decreased the AUC and Cmax of clopidogrel’s active metabolite both by 69% when compared to values obtained in HIV-negative subjects (n=12). In HIV-negative subjects (n=12), coadministration of clopidogrel and ritonavir (100 mg twice daily) decreased the AUC and Cmax of clopidogrel’s active metabolite by 51% and 48%. Importantly, the decrease in clopidogrel’s active metabolite lead to insufficient inhibition of platelet aggregation in 44% of the patients treated with clopidogrel and ritonavir or cobicistat. Consistently, the study in HIV-negative subjects showed that the average inhibition of platelet aggregation was decreased from 51% (clopidogrel alone) to 31% (clopidogrel + ritonavir). Of interest, the study with HIV-infected patients showed a comparable decrease in prasugrel’s active metabolite AUC (52% decrease), however this decrease did not impair prasugrel’s antiplatelet effect. The differential impact on clopidogrel and prasugrel pharmacodynamics effect is in line with clinical observations. Early thrombosis of a coronary stent was reported in a patient treated with darunavir/ritonavir concomitantly with clopidogrel while subsequent replacement of clopidogrel by prasugrel did not lead to novel stent thrombosis episodes. Taken together these data suggest that given the risk of diminished clopidogrel response, prasugrel should be preferred in presence of boosted regimens, unless the patient has a clinical condition which contraindicates its use in which case an alternative antiplatelet agent should be considered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cloxacillin is metabolised to a limited extent, and the unchanged drug and metabolites are excreted in the urine by glomerular filtration and renal tubular secretion.

Coadministration has not been studied. Clozapine is metabolized by CYPs 1A2, 2C19, 3A4, and to a lesser extent by CYPs 2C9 and 2D6. Lopinavir/ritonavir could potentially increase clozapine exposure. Monitor patient closely for toxicity. In addition, caution should be exercised as both drugs have possible risks of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but should be avoided. Cobimetinib is metabolised by CYP3A4 and UGT2B7. Cobimetinib concentrations are expected to increase due to strong inhibition of CYP3A4 by lopinavir/ritonavir. Itraconazole (a strong CYP3A4 inhibitor) increased cobimetinib AUC by 6.7-fold. A similar effect is expected with lopinavir/ritonavir and therefore coadministration is not recommended. In addition, caution should be exercised as both lopinavir and cobimetinib have a risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Cocaine is metabolized by several pathways, with metabolism to norcocaine by CYP3A4 being less than 10% of the overall metabolic clearance. Lopinavir/ritonavir could potentially increase concentrations of the parent compound. The clinical relevance is unknown as cocaine is metabolized by other non-CYP mediated pathways. Ensure the patient is aware of signs/symptoms of cocaine toxicity. In addition, caution should be exercised as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; known risk for cocaine).

Coadministration has not been studied. Codeine is a substrate of CYP2D6 (major) and CYP3A4. Ritonavir inhibits CYP2D6 at higher doses but at the 100 mg dose, ritonavir does not appear to markedly inhibit CYP2D6. While no a priori dose adjustment is required, the analgesic effect requires conversion of codeine to morphine via CYP2D6 and lopinavir/ritonavir could potentially reduce the analgesic efficacy.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The major route of elimination for coenzyme Q10 is by biliary and faecal excretion; only a small fraction is eliminated in the urine. Lopinavir/ritonavir is metabolised by CYP3A4. Coenzyme Q10 is unlikely to have a clinically significant effect on substrates of CYP3A4, UGTs and P-gp.

Coadministration is expected to increase colchicine concentrations. Ritonavir (100 mg twice daily) significantly increased colchicine Cmax (2.7-fold) and AUC (3.5-fold) when given with a single dose of colchicine (0.6 mg). Patients with renal or hepatic impairment should not be coadministered colchicine. A reduction in colchicine dosage or an interruption of colchicine treatment is recommended in patients with normal renal or hepatic function. When coadministered for treatment of gout flares, the recommended dosage is 0.6 mg (1 tablet) for 1 dose, followed by 0.3 mg (half tablet) 1 hour later. The dose is to be repeated no earlier than 3 days. When coadministered for prophylaxis of gout flares, if the original regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg once a day; if the original regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once every other day. When coadministered for treatment of familial Mediterranean fever (FMF) do not exceed a maximum daily dose of 0.6 mg (may be given as 0.3 mg twice a day).

Coadministration has not been studied. Metabolism of vitamin D to active metabolites occurs in the liver and kidneys, and is thought to involve CYP3A4 and CYP24A1. In vitro studies have shown rifampicin (an enzyme inducer) increased metabolism of vitamin D and introduction of 6',7'-dihydroxybergamottin (a CYP3A4 inhibitor in grapefruit juice) reversed the effects of rifampicin on vitamin D clearance. Inhibition of CYP3A by lopinavir/ritonavir is not expected to reduce the effect of vitamin D, but the consequence of CYP3A inhibition on the clinical effect of vitamin D is not known. However, no effect of antiretroviral therapy on the response to vitamin D supplementation was found in a PK modelling study.

Coadministration has not been studied. No interaction is expected with vitamin D when given with calcium or in a multivitamin preparation. Metabolism of vitamin D to active metabolites occurs in the liver and kidneys, and is thought to involve CYP3A4 and CYP24A1. In vitro studies have shown rifampicin (an enzyme inducer) increased metabolism of vitamin D and introduction of 6',7'-dihydroxybergamottin (a CYP3A4 inhibitor in grapefruit juice) reversed the effects of rifampicin on vitamin D clearance. Inhibition of CYP3A by lopinavir/ritonavir is not expected to reduce the effect of vitamin D, but the consequence of CYP3A inhibition on the clinical effect of vitamin D is not known. However, no effect of antiretroviral therapy on the response to vitamin D supplementation was found in a PK modelling study.

Coadministration has not been studied. Colesevelam is not absorbed from the gastrointestinal tract, is not metabolised and does not affect CYP enzymes. Lopinavir/ritonavir is metabolised by CYP3A4. However, given that colesevelam can reduce the gastrointestinal absorption of some drugs, colesevelam should be administered at least four hours before or after lopinavir/ritonavir to minimize the risk of reduced absorption.

Coadministration has not been studied. Colestyramine may delay or reduce the absorption of drugs. Administration of other drugs should be at least 1 hour before or 4-6 hours after colestyramine. [Note: this interaction is not specific for lopinavir/ritonavir, but for any medication taken with colestyramine.]

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Collagen hydrolysate is digested and absorbed as essential amino acids for use in essential physiological processes. Lopinavir/ritonavir is metabolised by CYP3A4. Collagen hydrolysate is unlikely to affect CYP3A4.

Coadministration with conjugated estrogens as hormone replacement therapy (HRT) has not been studied. Conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Coadministration could potentially decrease exposure of conjugated exposure due to induction of CYP1A2 and glucuronidation (rather than increase it due to inhibition of CYP3A4). Monitor for signs of estrogen deficiency. In contrast exposure of progestogens administered as part of HRT may increase. The clinical relevance of this is unknown but increased progestogen concentrations may be associated with a higher incidence of side effects. Note, use of conjugated estrogens as part of gender affirming treatment should be avoided as they are associated with high thromboembolic risk.

Coadministration has not been studied. Copanlisib is metabolised by CYP3A (~90%) and CYP1A1 (~10%). Lopinavir/ritonavir is metabolised by CYP3A4. Copanlisib does not inhibit or induce CYP3A4. However, lopinavir/ritonavir is a strong inhibitor of CYP3A4 and may increase copanlisib concentrations. Coadministration of copanlisib (60 mg i.v. infusion) and a strong CYP3A4 inhibitor (itraconazole, 200 mg once daily for 10 days) increased copanlisib AUC by 53% with no effect on Cmax (3% increase). A similar effect can be expected with lopinavir/ritonavir. The American product label for copanlisib states that if coadministration with strong CYP3A inhibitors cannot be avoided, to reduce the copanlisib dose from 60 mg to 45 mg.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Creatine monohydrate is not degraded during normal digestion and nearly 99% of orally ingested creatine monohydrate is either taken up by muscle or excreted in urine. Lopinavir/ritonavir is metabolised by CYP3A4. Creatine is unlikely to affect CYP3A4.

Coadministration has not been studied but should be avoided. Crizotinib is mainly metabolized by CYP3A4. Lopinavir/ritonavir is a strong inhibitor of CYP3A4 and is expected to increase crizotinib concentrations. Coadministration with ketoconazole (200 mg twice daily), a strong CYP3A inhibitor, increased crizotinib AUC and Cmax by 3.2-fold and 1.4-fold, respectively. A similar effect is expected with lopinavir/ritonavir and therefore coadministration is not recommended. In addition, both lopinavir and cobimetinib have a risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Although several constituents of Piper cubeba were shown to inhibit CYP3A4 in vitro, any additional effect on exposure of lopinavir in the presence of ritonavir is unlikely.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely with cyanocobalamin when given alone or in multivitamins. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine.

Coadministration has not been studied. The metabolism of cyclizine has not been fully described but may involve CYP2D6. Lopinavir/ritonavir is mainly metabolized by CYP3A4. Lopinavir is unlikely to inhibit or induce CYP2D6. However, ritonavir is a weak inhibitor of CYP2D6 when used as a pharmacokinetic booster and could potentially increase cyclizine exposure, although to a moderate extent. No a priori dosage adjustment is recommended.

Coadministration has not been studied. Cyclophosphamide is metabolized by two pathways. Activation (major pathway) to 4-hydroxycyclophosphamide is catalyzed by CYPs 2B6 (major), 2C9 and 3A4. Inactivation (minor, 10%) to the neurotoxic chloroacetaldehyde metabolite is performed mainly by CYP3A4. In vivo data indicate that ritonavir induces CYP2B6. In theory, lopinavir/ritonavir could potentially reduce the risk of neurotoxicity and increase the amount of drug available for the activation pathway which may increase the efficacy and the toxicity of cyclophosphamide (i.e., myelosuppression, nausea, vomiting). Careful monitoring of cyclophosphamide related side effects is recommended. Adjust dose if clinically necessary.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cycloserine is predominantly excreted renally via glomerular filtration.

Coadministration has not been studied. Cyproterone acetate is metabolized by CYP3A4 and concentrations may increase due to inhibition of CYP3A4 by lopinavir/ritonavir. A dose adjustment of cyproterone may be required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cytisine is primarily excreted renally as unchanged drug. There are no reports of CYP or transporter involvement and significant pharmacokinetic interactions are unlikely. Lopinavir/ritonavir is metabolised by CYP3A4.

A case report suggests that lopinavir/ritonavir has no clinically significant interaction with dabigatran. A reduced dabigatran dosage of 75 mg twice daily (due to the anticipated interaction with lopinavir/ritonavir) resulted in insufficient dabigatran plasma concentrations. Dabigatran concentrations comparable to historical data were achieved in this patient at a dosage of 110 mg twice daily. However, due to limited data, close clinical monitoring is recommended when ritonavir-boosted protease inhibitors are used with dabigatran particularly in patients with mild or moderate renal impairment as data with verapamil (a P-gp inhibitor) and dabigatran suggest the dabigatran dose might need to be reduced in presence of a P-gp inhibitor such as lopinavir/ritonavir. Note, dabigatran is not recommended in patients with severe renal impairment.

Coadministration has not been studied but is not recommended. Dabrafenib is metabolized by CYP3A4 and CYP2C8 and the active metabolites are metabolized by CYP3A4. Lopinavir/ritonavir is metabolized by CYP3A4 and is a strong inhibitor of CYP3A4 and therefore may increase dabrafenib concentrations. Coadministration of ketoconazole (another strong CYP3A4 inhibitor) and dabrafenib increased dabrafenib AUC and Cmax by 71% and 33%, respectively. The AUC of hydroxyl-dabrafenib and desmethyl-dabrafenib increased by 82% and 68%, respectively; Cmax of hydroxyl-dabrafenib and desmethyl-dabrafenib increased by 27% and 72%, respectively. In addition, dabrafenib is a strong inducer of CYP3A4 and may decrease lopinavir/ritonavir concentrations which may lead to loss of therapeutic effect and possible development of resistance Furthermore, lopinavir and dabrafenib have a risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied. Dacarbazine undergoes activation to MTIC primarily via CYP1A2 and to a lesser extent by CYP2E1, with CYP1A1 having a role in extrahepatic metabolism. In vitro data indicate that lopinavir/ritonavir induces CYP1A2. Lopinavir/ritonavir may increase the conversion to MTIC and thereby increase the efficacy and toxicity of dacarbazine. Monitor side effects.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dacomitinib is metabolised by CYP2D6 (~26%) to O-desmethyl dacomitinib, an active metabolite with similar activity to dacomitinib, whilst CYP3A4 (~6%) contributes to the formation of other minor metabolites. Lopinavir/ritonavir is a strong inhibitor of CYP3A4 and may increase dacomitinib concentrations. However, this is unlikely to be clinically significant as CYP3A4 contributes to dacomitinib metabolism only to a small degree.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dactinomycin is minimally metabolized, is concentrated in nucleated cells, and does not penetrate the blood-brain barrier. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapagliflozin is primarily metabolised by UGT1A9. Lopinavir/ritonavir may affect dapagliflozin due to UGT induction by ritonavir but a clinically relevant effect is not expected as coadministration of dapagliflozin with rifampicin (an inducer of several UGT enzymes) decreased dapagliflozin systemic exposure by 22% but had no clinically meaningful effect on 24-hour urinary glucose excretion. No dose adjustment is recommended. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Lopinavir/ritonavir is metabolized by CYP3A. Dapivirine is metabolized mainly by CYP3A4 and to a lesser extent by glucuronidation. However, the risk of drug-drug interactions is low with the dapivirine vaginal ring due to its low systemic exposure. Furthermore, dapivirine concentrations in vaginal fluid exceed the in vitro HIV IC99 by 1000-fold.

Metabolism of dapsone is mainly by N-acetylation with a component of N-hydroxylation, and is via multiple CYP P450 enzymes. Clinically significant interactions are unlikely, but can not be excluded.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daptomycin is eliminated renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Daratumumab, is an IgG1 monoclonal antibody and is likely to be eliminated via intracellular catabolism, similarly to endogenous IgG. Lopinavir/ritonavir is metabolized by CYP3A4.

Coadministration has not been studied but is contraindicated. Daridorexant is mainly metabolised by CYP3A4. Lopinavir/ritonavir is metabolised by CYP3A4. Daridorexant is a weak inhibitor of CYP3A4 but is unlikely to have a clinically significant effect on lopinavir/ritonavir. However, lopinavir/ritonavir is a strong CYP3A4 inhibitor and is expected to significantly increase daridorexant concentrations. Coadministration of daridorexant (25 mg) and the moderate CYP3A4 inhibitor diltiazem (240 mg once daily) increased daridorexant AUC and Cmax by 2.4- and 1.4-fold, respectively. No clinical study was conducted with a strong CYP3A4 inhibitor. Coadministration with strong CYP3A4 inhibitors is contraindicated in the European product label for daridorexant, whereas the American product label recommends to avoid coadministration.

Coadministration has not been studied. Darifenacin is metabolized by CYP3A4 and CYP2D6 and coadministration is likely to increase concentrations. A 5-fold increase in darifenacin exposure was seen with ketoconazole (a strong inhibitor of CYP3A4) and the magnitude of the interaction could be even more pronounced in poor metabolizer individuals. The European Summary of Product Characteristics for darifenacin contraindicates its use with potent CYP3A4 inhibitors (such as lopinavir/ritonavir), but the US Prescribing Information recommends that the dose of darifenacin should not exceed 7.5mg when coadministered with potent CYP3A4 inhibitors.

Coadministration has not been studied. Darolutamide is primarily metabolised by CYP3A4, and to a lesser extent by UGT1A9 and UGT1A1, and is a substrate of P-gp. Lopinavir/ritonavir is metabolized by CYP3A4. Darolutamide is a weak inducer of CYP3A4 but is unlikely to have a clinically significant effect on lopinavir/ritonavir. Inhibition of CYP3A4 and P-gp by lopinavir/ritonavir may increase darolutamide concentrations. No a priori dose adjustment is required but monitor for adverse effects. Note, androgen deprivation treatment may prolong the QT interval. Caution should be taken when using with antiretroviral drugs that can potentially prolong the QT interval such as lopinavir.

Coadministration of darunavir (1200 mg twice daily, with or without 100 mg ritonavir) had no significant effect on lopinavir pharmacokinetics but decreased darunavir AUC by ~40% (relative to data obtained with darunavir/ritonavir 600/100 mg alone). Due to decreased darunavir exposure, appropriate doses of the combination have not been established and it is not recommended to coadminister lopinavir/ritonavir with darunavir.

Symtuza (darunavir, cobicistat, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. Furthermore, adding a dose of lopinavir/ritonavir has not been studied with respect to safety, efficacy and pharmacokinetics.

Darunavir/cobicistat coformulations (Rezolsta; Prezcobix) should not be administered concurrently with lopinavir co-formulated with ritonavir due to similar effects of cobicistat and ritonavir on CYP3A4.

Coadministration has not been studied but should be avoided. Dasatinib is metabolized by CYP3A4 and coadministration may significantly increase exposure to dasatinib concentrations. In addition, both drugs have a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website. If coadministration is unavoidable, close monitoring for toxicity and QT prolongation is required. The US product information for dasatinib recommends a dose reduction to 20 mg daily (for patients taking dasatinib 100 mg) and to 40 mg (for patients taking dasatinib 140 mg) in presence of strong inhibitors of CYP3A4.

A clinical study reported that ritonavir had no effect on daunorubicin (liposomal) pharmacokinetics. An in vitro study has shown that daunorubicin was able to inhibit metabolism mediated by CYP3A4, but was unlikely to cause clinically significant drug interactions via this mechanism. There is therefore little potential for pharmacokinetic interaction. Damage to the myocardium is one of the major risks of daunorubicin treatment and may include dose-independent supraventricular arrhythmias (sinus tachycardia, premature ventricular contractions, AV-block) and/or non-specific ECG abnormalities. Caution must be used when prescribing lopinavir/ritonavir and medicinal products known to induce QT or PR interval prolongation.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The primary route of decitabine metabolism is likely by cytidine deaminase. Decitabine is a prodrug and is activated intracellularly through sequential phosphorylation via phosphokinases activities to the active triphosphate. Lopinavir/ritonavir is metabolised by CYP3A4. Decitabine does not inhibit or induce CYP enzymes.

Coadministration has not been studied but should be avoided. Deferasirox is mainly glucuronidated by UGT1A1 and to a lesser extent by UGT1A3; CYP-mediated metabolism appears to be minor (~8%). Lopinavir/ritonavir is metabolised by CYP3A4. Deferasirox is a weak inducer of CYP3A4 and was shown to reduce midazolam exposure by 17%, although it is unlikely to significantly decrease lopinavir/ritonavir concentrations. However, ritonavir induces UGT and may decrease deferasirox concentrations leading to a possible decrease in efficacy. Avoid concomitant use of UGT inducers with deferasirox. If coadministration with ritonavir is unavoidable, the American product label advises to consider increasing the deferasirox dose by 50%, and to monitor serum ferritin levels and clinical responses for further dose modification.

Coadministration has not been studied. Deflazacort is immediately metabolised by plasma esterases to the active metabolite (21-desdeflazacort) which is then metabolised mainly by CYP3A4 to several inactive metabolites which are excreted in the urine (~70%) and faeces (~30%). Lopinavir/ritonavir is metabolised by CYP3A4. Deflazacort and 21-desdeflazacort do not inhibit or induce CYP3A4. However, lopinavir/ritonavir is a strong inhibitor of CYP3A4 and may increase exposure of 21-desdeflazacort. Coadministration of deflazacort and clarithromycin (a strong CYP3A4 inhibitor), increased total exposure of 21-desdeflazacort by about 3-fold. The European product label for deflazacort recommends coadministration with CYP3A inhibitors should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects. The US product label suggests a dose reduction to one third of the normal recommended deflazacort dosage with moderate/strong CYP3A4 inhibitors.

Delamanid is primarily metabolised by albumin to DM-6705; metabolism of DM-6705 to other metabolites is thought to involve pathways mediated by CYP enzymes, including CYP3A4. Co-administration of delamanid (100 mg twice daily) and lopinavir/ritonavir (400/100 mg twice daily) had no effect on lopinavir Cmax or AUC (increases of 5% and 4%), but increased delamanid Cmax and AUC by 18% and 22%. DM-6705 exposure has been reported to increase by 25-30% with lopinavir/ritonavir. QTc prolongation has been reported with delamanid (and is very closely correlated with the metabolite DM-6705), therefore, caution is advised due to potent CYP3A4 inhibition and due to the risk of QT prolongation associated with both drugs. If coadministration is considered necessary, frequent ECG monitoring is recommended throughout the full delamanid treatment period (for example, at least fortnightly for the first month and if the QTc interval remains within normal range to reduce this to monthly thereafter).

Coadministration of lopinavir/ritonavir (400/100 mg twice daily for 10 days) and desipramine (100 mg single dose) had no clinically significant effect on desipramine (9% decrease in Cmax, 5% increase in AUC). However, caution should be exercised as both drugs have possible risks of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desloratadine is metabolized to the active metabolite 3-hydroxydesloratadine, which is subsequently glucuronidated. The enzyme(s) responsible for the formation of the active metabolite have not been identified, but no clinically relevant interactions have been observed with inhibitors of CYP enzymes. Lopinavir/ritonavir is metabolized by CYP3A4. Desloratadine does not inhibit CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desmopressin undergoes no significant hepatic metabolism and is not a substrate for CYP enzymes. Lopinavir/ritonavir is metabolised by CYP3A4. Desmopressin does not inhibit CYP enzymes and no metabolic drug interactions are expected.

Desogestrel is a prodrug that is activated to etonogestrel by CYP2C9 (and possible CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Coadministration of a combined oral contraceptive (COC) containing ethinylestradiol and desogestrel (30/150 µg once daily) with lopinavir/ritonavir (individualised dose up to 400/100 twice daily) was studied in 16 HIV positive Thai females. Lopinavir and ritonavir Ctrough decreased by 26% and 31%, respectively. When compared to historical data from HIV-negative subjects (n=14), ethinylestradiol and etonogestrel Ctrough decreased by 32% and 8%, respectively. Ovulation was reported to be suppressed, however, the study reports a high variability in hormone levels. Caution is recommended and additional contraceptives measures should be used.

Coadministration with a desogestrel-containing progestogen-only pill (POP) has not been studied. Desogestrel is a prodrug that requires activation to etonogestrel. Activation to etonogestrel is by CYP2C9 (and possibly CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Coadministration is predicted to increase etonogestrel and, based on studies with norethisterone used as a POP, the contraceptive efficacy of a desogestrel POP is unlikely to be compromised by lopinavir.

Coadministration has not been studied. Dexamethasone is metabolized by CYP3A4. Lopinavir/ritonavir may increase dexamethasone concentrations due to inhibition of CYP3A4. A dose reduction of the glucocorticoid may be necessary with monitoring for symptoms of Cushing's syndrome. Dexamethasone is a dose-dependent inducer of CYP3A4 and is a moderate CYP3A4 inducer at doses above 16 mg. Chronic or high doses of dexamethasone may decrease lopinavir/ritonavir plasma concentrations due to CYP3A4 induction with the possible loss of therapeutic effect and development of resistance. Use with caution.

Coadministration has not been studied. Dexamethasone is metabolized by CYP3A4. Lopinavir/ritonavir may increase dexamethasone concentrations due to inhibition of CYP3A4. A dose reduction of the glucocorticoid may be necessary with monitoring for symptoms of Cushing's syndrome. Dexamethasone is a weak CYP3A4 inducer at a low dose and is unlikely to have a clinically significant effect on lopinavir/ritonavir. Note, it is expected that the risk of Cushing’s syndrome is less likely to occur when using dexamethasone at a low dose and for a short treatment duration as compared to higher doses and long treatment duration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dexketoprofen is mainly excreted as glucuronide conjugates; CYP2C8/9 plays a minor role in metabolism. Lopinavir/ritonavir is metabolised by CYP3A4. Dexketoprofen is unlikely to affect CYP3A4. Inhibition or induction of UGTs and CYPs by lopinavir/ritonavir is unlikely to have a significant impact on dexketoprofen exposure as it is likely multiple UGTs are involved in the metabolism of dexketoprofen and CYP2C8 represents a minor metabolic pathway.

Lopinavir can be coadministered with acid reducing agents with no dose adjustment. No reduction in lopinavir or ritonavir trough concentrations were observed over 48 weeks in HIV+ subjects receiving lopinavir/ritonavir with an acid reducing agent (antacids, proton pump inhibitors or H2 receptor antagonists). 

Coadministration has not been studied. Dexmedetomidine undergoes extensive hepatic biotransformation through direct glucuronidation (mainly via UGT1A4, 2B10) and cytochrome P450 (mainly 2A6). Study data indicate that ritonavir decreases exposure of lamotrigine, a UGT1A4 probe substrate. Lopinavir/ritonavir could potentially decrease dexmedetomidine concentrations. No a priori dosage adjustment is recommended but monitor clinical effect. In addition, both drugs have possible risks of QT prolongation and/or TdP on the CredibleMeds.org website. 

Coadministration of lopinavir/ritonavir and dextromethorphan increased the AUC of dextromethorphan. Dextromethorphan is metabolized by CYP2D6. Lopinavir/ritonavir is metabolised by CYP3A4. Dextromethorphan does not inhibit or induce CYP3A4. However, coadministration of lopinavir/ritonavir (400/100mg twice daily) and dextromethorphan (30 mg) in 24 patients, increased of dextromethorphan AUC by 1.23-fold. If coadministration is necessary, use with caution and a dose reduction of dextromethorphan may be required based on clinical response.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diclofenac is partly glucuronidated by UGT2B7 and partly oxidized by CYP2C9. In vivo data indicate that lopinavir/ritonavir is a weak inducer of CYP2C9, however a dose adjustment is unlikely to be required for diclofenac.

Coadministration has not been studied. Based on limited data concerning the metabolism/elimination and toxicity profile of diethylcarbamazine, there is little potential for interaction with lopinavir/ritonavir.

Use with caution as both lopinavir/ritonavir and digoxin prolong the PR interval. Coadministration may increase digoxin concentrations due to P-gp inhibition. The increased digoxin level may lessen over time as P-gp induction develops. Caution is warranted. Clinical and therapeutic drug monitoring of digoxin concentrations is recommended, if available.

Coadministration has not been studied. Dihydrocodeine is converted to dihydromorphine (active metabolite) via CYP2D6, to dihydrocodeine-6-glucuronide via UGT2B7 (major pathway) and to nordihydrocodeine via CYP3A4. The analgesic effect appears to be primarily due to the parent compound. Lopinavir/ritonavir could potentially increase dihydrocodeine exposure (inhibition of CYP3A4 and CYP2D6) and increase the conversion to dihydrocodeine-6-glucuronide (induction of UGT2B7). The net clinical effect of this interaction is difficult to predict. No a priori dose adjustment is required, but monitoring for analgesic effect and for signs of opiate toxicity may be required as clinically indicated.

Coadministration of dihydroergotamine and lopinavir/ritonavir is contraindicated due to potential for serious and/or life-threatening reactions such as acute ergot toxicity.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Diloxanide furoate is largely hydrolysed under the combined action of bacterial and gut esterases and consequently glucuronidated. No clinically-significant drug interactions are known, and significant interactions with antiretrovirals are unlikely.

Coadministration has not been studied. Diltiazem is metabolized by CYP3A4 and CYP2D6, and is a moderate inhibitor of CYP3A4. Coadministration may increase diltiazem concentrations. Use with caution as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; conditional risk for diltiazem). If coadministration is necessary, clinical monitoring including ECG assessment is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dimethyl fumarate is metabolized by esterases before entering the blood stream. Further metabolism occurs though the TCA cycle. Lopinavir/ritonavir is metabolised by CYP3A4. Dimethyl fumarate is unlikely to have a clinically significant effect on substrates of CYPs, UGTs and P-gp.

Coadministration has not been studied. Diphenhydramine is mainly metabolized by CYP2D6. Lopinavir/ritonavir could potentially increase diphenhydramine concentrations although to a moderate extent. No a priori dosage adjustment is recommended.

Coadministration has not been studied. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Coadministration could potentially decrease dipyridamole exposure due to induction of glucuronidation, thereby reducing the antiplatelet effect.

Coadministration has not been studied and is not recommended. Disopyramide is metabolized by CYP3A4 (25%) and 50% of the drug is eliminated unchanged in the urine. Coadministration may increase disopyramide exposure and thereby the risk of cardiac arrhythmias. Caution should be exercised as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; known risk for disopyramide).

Coadministration is contraindicated with lopinavir/ritonavir ORAL SOLUTION. No interaction expected with lopinavir/ritonavir tablets.

Coadministration with lopinavir/ritonavir may increase concentrations of docetaxel and increase the risk of severe toxicities. There have been several case reports of severe haematological and cutaneous toxicity when coadministered with ritonavir, a potent CYP3A inhibitor. Ideally avoid coadministration with boosted protease inhibitors or consider using an alternative taxane.

Coadministration has not been studied and is not recommended. Dofetilide is metabolized to a small degree by CYP3A4 and therefore lopinavir/ritonavir could potentially increase dofetilide exposure and thereby increase the risk of cardiac arrhythmias. Caution should be exercised as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; known risk for dofetilide).

Coadministration has not been studied. Dolasetron is converted by carbonyl reductase to its active metabolite, hydrodolasetron, which is mainly glucuronidated (60%) and metabolized by CYP2D6 (10-20%) and CYP3A4 (<1%). Coadministration could potentially increase dolasetron concentrations although this is unlikely to be clinically meaningful since CYP-mediated metabolism is minor and dolasetron has a wide therapeutic margin. However, caution should be exercised as both drugs have possible risks of QT prolongation and/or TdP on the CredibleMeds.org website.

Lopinavir/ritonavir has no clinically significant effect on the pharmacokinetics of dolutegravir. Coadministration of lopinavir/ritonavir (400/100 mg twice daily) and dolutegravir (30 mg once daily had no effect on dolutegravir Cmax, and decreased AUC and Ctrough by 3% and 6%. Coadministration with lopinavir/ritonavir and etravirine had no significant effect on dolutegravir exposure (AUC, Cmax and Ctrough increased by 10%, 7% and 28%, respectively). When compared to historical data, dolutegravir did not appear to affect the pharmacokinetics of lopinavir or ritonavir. No dose adjustment is necessary.

Dolutegravir/lamivudine/tenofovir-DF is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with lopinavir/ritonavir would be possible from a pharmacokinetic standpoint but with close monitoring for tenofovir-associated adverse events. Coadministration of lopinavir/ritonavir and dolutegravir decreased dolutegravir AUC and C24 by 4% and 6% and had no effect on Cmax; there was no effect on lopinavir or ritonavir. No change in the pharmacokinetics of lopinavir was observed with stavudine and lamivudine in clinical studies. Coadministration of tenofovir-DF (300 mg once daily) and lopinavir/ritonavir (400/100 mg twice daily) increased tenofovir-DF AUC by 32%, Cmin increased by 51%, and there was no change in Cmax. A higher risk of renal impairment has been reported in patients receiving tenofovir-DF and a ritonavir boosted protease inhibitor. No dose adjustment is recommended, but close monitoring of renal function and for tenofovir-associated adverse reactions is required.

Triumeq (dolutegravir, abacavir, lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with lopinavir/ritonavir would be possible from a pharmacokinetic standpoint. Coadministration of lopinavir/ritonavir and dolutegravir decreased dolutegravir AUC and C24 by 4% and 6% and had no effect on Cmax; there was no effect on lopinavir or ritonavir. Coadministration of lopinavir/ritonavir and abacavir decreased abacavir AUC by 32%. No change in the pharmacokinetics of lopinavir was observed with lamivudine in clinical studies.

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV 1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with lopinavir/ritonavir would be possible from a pharmacokinetic standpoint. The European product label for Dovato advises that no dose adjustment is necessary with lopinavir/ritonavir. Coadministration of lopinavir and dolutegravir decreased dolutegravir AUC and C24 by 4% and 6% and had no effect on Cmax; there was no effect on lopinavir or ritonavir. No change in the pharmacokinetics of lopinavir was observed with stavudine and lamivudine in clinical studies.

Juluca (dolutegravir/rilpivirine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. However, in specific clinical situations where an intensification of HIV treatment is needed, coadministration with lopinavir/ritonavir would be possible from a pharmacokinetic standpoint. Coadministration of lopinavir/ritonavir (400/100 mg twice daily) and dolutegravir (30 mg once daily had no effect on dolutegravir Cmax, and decreased AUC and Ctrough by 3% and 6%. Coadministration of rilpivirine (150 mg once daily) and lopinavir/ritonavir (400/100 mg twice daily) increased rilpivirine Cmax, AUC and Cmin by 29%, 52% and 74%, respectively. Lopinavir Cmax, AUC and Cmin decreased by 4%, 1% and 11%, respectively. [Note: this interaction study has been performed with a dose higher than the licensed dose for rilpivirine assessing the maximal effect on the co-administered drug. The dosing recommendation is applicable to the licensed dose of rilpivirine 25 mg once daily.] Rilpivirine has been associated with prolongation of the QTc interval at supra-therapeutic doses but equivalent rilpivirine concentrations are unlikely to occur during coadministration with lopinavir/ritonavir. However, the product labels for Juluca indicate that rilpivirine should be used with caution in combination with drugs with a known risk of Torsade de Pointes. Lopinavir has a possible risk of QT prolongation and/or TdP on the CredibleMeds.org website.

Coadministration has not been studied and is contraindicated with potent CYP3A4 inhibitors, such as lopinavir/ritonavir. Domperidone is mainly metabolized by CYP3A4. Lopinavir/ritonavir could potentially increase domperidone exposure and increase the risk of cardiac adverse effects. Both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir; known risk for domperidone).

Coadministration has not been studied. Donepezil is metabolized by CYP3A4 and CYP2D6 (minor). A 30% increase in donepezil exposure has been reported in presence of ketoconazole, a strong CYP3A4 inhibitor. A similar effect is expected with the strong CYP3A4 inhibitor lopinavir/ritonavir. No a priori dose modification is required but monitoring for increased side effects is recommended. Furthermore, caution should be exercised as both drugs have risks of QT prolongation and/or TdP on the CredibleMeds.org website (possible risk for lopinavir/ritonavir and known risk for donepezil). If coadministration is necessary, ECG monitoring is recommended.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dopamine is metabolised in the liver, kidneys, and plasma by monoamine oxidase (MAO) and catechol-O-methyltransferase to inactive compounds. About 25% of a dose of dopamine is metabolised to norepinephrine within the adrenergic nerve terminals. There is little potential for dopamine to affect disposition of antiretrovirals, or to be affected if coadministered with antiretrovirals.