Coadministration increased abacavir AUC and Cmax by 3% and 6%, respectively; Cmin decreased by 17%. Studies are required to relate the change in plasma abacavir exposure to the active intracellular carbovir triphosphate.

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 but based on metabolism and clearance a clinically significant interaction is unlikely as acenocoumarol is mainly metabolized by CYP2C9.

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 raltegravir 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 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.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. 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 raltegravir via modulation of, or competition for metabolic or elimination pathways.

Coadministration has not been studied. African potato was shown to inhibit CYP3A4 and P-gp in vitro and to activate PXR suggesting that inhibition may occur initially followed by induction of CYP3A4, P-gp and possibly UGT when used for extended periods. Use with caution as African potato could decrease concentrations of raltegravir. Therapeutic drug monitoring of raltegravir is recommended.

Coadministration has not been studied, but based on metabolism and clearance a clinically significant interaction is unlikely. Albendazole is metabolized by CYP3A4 and by the flavine-containing monooxygenase system.

Coadministration has not been studied but based on metabolism and clearance, as well as limited drug-drug interaction data, a clinically significant interaction is unlikely. Raltegravir is metabolized by UGT1A1. An interaction is unlikely as albuvirtide is a peptide which is eliminated by catabolism to its constituent amino acids.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs there is little potential for interaction. Alcuronium is predominantly eliminated unchanged via the kidneys.

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 has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Raltegravir is not expected to affect the pharmacokinetics of opioid analgesics.

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. 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. Raltegravir does not interfere with ambrisentan metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Aminophylline is a complex of theophylline and ethylenediamine and is given for its theophylline activity. Theophylline is mainly metabolized by CYP1A2.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Ampicillin is predominantly eliminated unchanged via renal pathways.

Coadministration of raltegravir (400 mg twice daily or 1200 mg once daily) with ALUMINIUM and/or MAGNESIUM antacids is not recommended as the divalent metal cations reduce raltegravir absorption by chelation. Taking an aluminium and magnesium antacid within 6 hours of raltegravir administered twice daily decreased raltegravir trough concentrations by ~50-60%. Coadministration of CALCIUM CARBONATE antacids (1000 mg x 3 tabs) did not have a clinically meaningful effect on twice daily raltegravir (raltegravir Cmax, AUC and Cmin decreased by 52%, 55% and 32%; n=24) and no dose adjustment is required. However, coadministration of calcium carbonate antacids (1000 mg x 3 tabs) had a clinically meaningful effect on once daily raltegravir (raltegravir Cmax, AUC and Cmin decreased by 2%, 10% and 57%). Therefore, coadministration of calcium carbonate antacids with once daily raltegravir is not recommended. If use of a calcium carbonate antacid is unavoidable then it should be with twice daily raltegravir. However, it is important to note that the recommendation with raltegravir 400 mg twice daily is based on short term or 'when required' use of antacids and clinical judgement should be applied to patients on long term use of calcium carbonate with raltegravir 400 mg twice daily.

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 based on metabolism and clearance a clinically significant interaction is unlikely. Apixaban is metabolized by CYP3A4 and to a lesser extent CYP1A2, CYP2C8, CYP2C9 and CYP2C19, but raltegravir is mainly metabolized by UGT1A1.

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. Drug-drug interactions studies performed with substrates of different cytochromes and P-glycoprotein (i.e., acetaminophen, lidocaine, warfarin, digoxin) indicate that argatroban has a low potential to cause drug-drug interactions and therefore is unlikely to alter the exposure of raltegravir.

Coadministration has not been studied. 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. A pharmacokinetic interaction is unlikely with raltegravir and vitamin C itself as raltegravir does not interfere with this metabolic pathway. However, ascorbic acid can be found in multivitamin preparations which may also contain polyvalent cations. As the effect of cationic complexation with raltegravir cannot be excluded, caution is recommended as raltegravir concentrations may be reduced.

This interaction has not been studied. Based on the metabolic profiles of both drugs, there is little potential for pharmacokinetic interaction. 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 twice daily raltegravir and atazanavir alone has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of raltegravir (400 mg twice daily) and atazanavir/ritonavir increased raltegravir AUC (41%), Cmax (24%) and Cmin (77%). However, concomitant use of twice daily raltegravir and atazanavir/ritonavir did not result in a unique safety signal in clinical studies, therefore, no dose adjustment of raltegravir is required when given twice daily. Coadministration of raltegravir (1200 mg single dose) and atazanavir alone increased raltegravir AUC (67%), Cmax (16%) and Cmin (26%). The US product label for raltegravir states that no dose adjustment is required with atazanavir and once daily raltegravir, however, the European label does not recommend coadministration with once daily raltegravir.

Coadministration with atazanavir/cobicistat has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Coadministration of atazanavir/ritonavir increased raltegravir AUC (41%), Cmax (24%) and Cmin (77%). However, concomitant use of raltegravir and atazanavir/ritonavir did not result in a unique safety signal in clinical studies, therefore, no dose adjustment of raltegravir is required. Atazanavir/cobicistat is expected to produce a similar effect on raltegravir. No dose adjustment is required for raltegravir if co-administered with atazanavir/cobicistat. Note: coadministration of once daily raltegravir (1200 mg once daily) is not recommended. Coadministration of raltegravir (1200 mg single dose) and atazanavir alone increased raltegravir AUC (67%), Cmax (16%) and Cmin (26%).

Coadministration of raltegravir (400 mg twice daily) and atazanavir/ritonavir increased raltegravir AUC (41%), Cmax (24%) and Cmin (77%). However, concomitant use of twice daily raltegravir and atazanavir/ritonavir did not result in a unique safety signal in clinical studies, therefore, no dose adjustment of raltegravir is required when given twice daily. Coadministration of raltegravir (1200 mg single dose) and atazanavir alone increased raltegravir AUC (67%), Cmax (16%) and Cmin (26%). The US product label for raltegravir states that no dose adjustment is required with atazanavir/ritonavir and once daily raltegravir, however, the European label does not recommend coadministration with once daily raltegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as atenolol is mainly eliminated unchanged by the kidney, both by glomerular filtration and active secretion via the renal transporters OCT2 and MATE1.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Raltegravir is not expected to affect the pharmacokinetics of statins.

This interaction has not been studied. Based on the metabolism/elimination profiles of both drugs, there is little potential for interaction 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 raltegravir 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. Avanafil is primarily metabolized by CYP3A4 and does not inhibit or induce UGTs.

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 has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Beclometasone is a pro-drug which is not metabolised by CYP450 but is hydrolysed via esterase enzymes to the highly active metabolite beclometasone-17-monopropionate.

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. Benazepril is rapidly hydrolyzed to its active metabolite benazeprilat which is eliminated predominantly renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bendroflumethiazide is eliminated by hepatic metabolism (70%, exact pathway not known) and excreted unchanged in the urine (30%) via OAT1 and OAT3. 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. 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. A case study of a patient taking an antiretroviral regimen of tenofovir, emtricitabine and raltegravir reported no clinical or laboratory adverse events when the patient received benznidazole 5 mg/kg daily for 90 days. At the end of treatment, the patient’s viral load remained undetectable, and CD4 count was maintained.

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

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. Betamethasone is metabolized by CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Betrixaban is largely eliminated unchanged through biliary secretion via P-gp and raltegravir does not inhibit or induce P-gp.

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. 

Biktarvy (bictegravir, 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, coadministering two integrase inhibitors (i.e., bictegravir and raltegravir is unlikely to be of clinical benefit.

Coadministration has not been studied but based on limited information concerning the metabolism and clearance of biperiden, there is little potential for clinically significant interaction. Limited human data suggest biperiden undergoes hydroxylation in the liver.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No effect on raltegravir is expected as in vitro studies suggest black cohosh is unlikely to affect UGT1A1 at clinically relevant concentrations.

No dose modification of raltegravir required.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Bupivacaine is predominantly metabolized via CYP3A4.

Coadministration of buprenorphine/naloxone and raltegravir (400 mg twice daily) had no significant effect on the AUC and Cmax of buprenorphine, norbuprenorphine and naloxone. Raltegravir AUC and Cmax did not differ to historical controls. No dose adjustment is required with buprenorphine/naloxone and raltegravir.

Coadministration has not been studied. Calcium folinate is the calcium salt of 5-formyl tetrahydrofolic acid, an active metabolite of folinic acid. In theory, calcium could chelate with raltegravir and potentially decrease the amount of raltegravir available to bind to the active site of the HIV integrase. However, given that the extent of chelation is dependent on the amount of calcium, this risk is predicted to be low when administering calcium folinate in small doses at frequent intervals. Since calcium is distributed rapidly, separating the intake of raltegravir from the IV administration of calcium folinate by 2 hours should eliminate any risk of chelation.

There are no studies of raltegravir and calcium supplements when given, for example, as an adjunct to specific therapies or to correct calcium deficiency. The daily dose of a calcium supplement may vary - often between 1 g and 3 g per day. It is known that raltegravir binds to divalent cations such as calcium and forms a complex at the level of the gastro-intestinal tract which results in less raltegravir being absorbed. A case report describes virological failure in a patient on raltegravir-containing regimen who was commenced on calcium carbonate (1 g vitamin D3 400 IU 3 times/day) for prevention of osteoporosis. Therapeutic drug monitoring at the time of virological failure showed lower than expected raltegravir concentrations at 5 hours post dose. However, coadministration of calcium carbonate antacids (1000 mg x 3 tabs) was not considered to have a clinically meaningful effect on twice daily raltegravir (raltegravir Cmax, AUC and Cmin decreased by 52%, 55% and 32%; n=24) and no dose adjustment is considered necessary. If possible, administration of raltegravir 400 mg twice daily should be separated by at least 4 hours from a calcium supplement (more important with higher doses). In addition, there was a more pronounced reduction in raltegravir Cmin when raltegravir was administered once daily with a calcium carbonate antacid compared to a twice daily regimen. A similar effect for calcium supplements cannot be excluded and, therefore, twice daily administration of raltegravir should be preferred. Note, for recommendations for calcium carbonate when used as an antacid, please search for interactions with "antacids".

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Canagliflozin is primarily metabolised by UGT1A9 and UGT2B4 which are not affected by raltegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cannabidiol is mainly metabolized by CYP3A4 and CYP2C19 and is unlikely to significantly inhibit UGT1A1 or intestinal transporters in the range of doses in clinical use. Raltegravir does not inhibit or induce UGT1A1.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Capreomycin is predominantly excreted via the kidneys as unchanged drug.

Coadministration has not been studied but could potentially decrease raltegravir concentrations as it is mainly glucuronidated by UGT1A1 and in vitro data suggest that carbamazepine induces UGT1A1. Coadministration of once daily raltegravir (1200 mg once daily) is not recommended as strong inducers are expected to have a more pronounced effect on raltegravir Cmin when raltegravir is given once daily. The US product label for raltegravir does not recommended coadministration with twice daily raltegravir. However, if coadministration with carbamazepine is unavoidable, raltegravir should be used as a twice daily regimen with close monitoring of antiretroviral response. Monitor raltegravir plasma concentrations (when possible).

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. Cat’s claw was demonstrated to strongly inhibit CYP3A4 in vitro but has also been shown to induce CYP3A4 activity in vitro. No interaction is expected as raltegravir does not undergo CYP3A4 metabolism.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Cefalexin is predominantly eliminated unchanged via the kidneys.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Cefazolin is predominantly eliminated unchanged via the kidneys.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Cefixime is predominantly eliminated unchanged via renal glomerular filtration.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Cefotaxime is predominantly eliminated unchanged via the kidneys.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Ceftazidime is predominantly eliminated unchanged via renal glomerular filtration.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. 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. 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 but based on the metabolism and clearance a clinically significant interaction is unlikely. Chloramphenicol is predominantly metabolized by glucuronidation mediated by UGT2B7, and raltegravir is eliminated mainly via a UGT1A1-mediated glucuronidation pathway. In vitro studies indicated that raltegravir is not an inhibitor of UGT1A1 and UGT2B7, and there is little potential for interaction when chloramphenicol and raltegravir are coadministered.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlorphenamine is predominantly metabolized in the liver via CYP2D6.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ciclesonide is a pro-drug activated by esterases in the lungs to des-ciclesonide which then undergoes CYP3A4-mediated metabolism. Raltegravir does not interact with ciclesonide metabolism.

Coadministration has not been studied but a clinically significant interaction is not expected. Coadministration of famotidine and twice daily raltegravir (400 mg twice daily) increased raltegravir AUC, Cmax and C12h by 44%, 60% and 6%. Population PK analysis showed that the effect of gastric pH altering agents on the pharmacokinetics of once daily raltegravir was minimal (~9% decrease in relative bioavailability), and was not statistically or clinically significant. Concomitant use of raltegravir with proton pump inhibitors and H2 blockers did not result in a unique safety signal in Phase 3 studies. No dose adjustment is required with twice daily or once daily raltegravir.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Clobazam is metabolised by CYP3A4 (major) and CYP2B6 and CYP2C19 (minor) to the active metabolite N-desmethylclobazam, which is metabolised by CYP2C19.

Coadministration has not been studied but based on metabolism and clearance a clinically relevant drug interaction is unlikely with the topical use of clobetasol.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. CYP2D6 is thought to have a role in clomifene metabolism.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Raltegravir is not expected to affect the pharmacokinetics of opioid analgesics.

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. There is little potential for interaction with raltegravir via modulation of, or competition for, metabolic pathways. No interaction is expected with vitamin D when given as a single agent (i.e. not with calcium or in a multivitamin preparation) or as an injection. However, colecalciferol can be found in multivitamin preparations which may also contain polyvalent cations. As the effect of cationic complexation with raltegravir cannot be excluded, caution is recommended with multivitamin preparations as raltegravir concentrations may be reduced.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. There is no evidence to suggest that Piper cubeba impacts UGTs.

Coadministration has not been studied. Cyanocobalamin undergoes enterohepatic recycling and is excreted almost entirely in the urine. No interaction is expected with vitamin B12 when given as a single agent (i.e. not in a multivitamin preparation) or as an injection. However, vitamin B12 can be found in multivitamin preparations which may also contain polyvalent cations. As the effect of cationic complexation with raltegravir cannot be excluded, caution is recommended as raltegravir concentrations may be reduced.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Cycloserine is predominantly excreted renally via glomerular filtration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cyproterone acetate is metabolized by CYP3A4.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dapagliflozin is primarily metabolised by UGT1A9 which is not affected by raltegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Darifenacin is metabolized by CYP3A4 and CYP2D6.

Some clinical trials with darunavir/ritonavir suggest that raltegravir may cause a modest decrease in darunavir plasma concentrations however this effect does not appear to be clinically relevant. Raltegravir and darunavir/cobicistat can be administered without dose adjustments.

Symtuza 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 raltegravir would be possible from a pharmacokinetic standpoint. No significant interactions are expected with raltegravir and darunavir/cobicistat, emtricitabine or tenofovir alafenamide.

No dose adjustment is required when raltegravir 400 mg twice daily or 1200 mg once daily is coadministered. Population data from HIV+ subjects suggest that coadministration of raltegravir and darunavir/ritonavir is associated with lower darunavir trough concentrations. However, the effect of raltegravir on darunavir plasma concentrations did not appear to be clinically meaningful. Limited data from 6 healthy subjects indicate that coadministration of twice daily raltegravir with darunavir/ritonavir decreased raltegravir AUC (29%) and Cmax (33%), but increased Cmin by 38%. Darunavir pharmacokinetics were similar to historical data. Contrary to clinical experience in HIV+ patients, 8/18 subjects presented with a clinical adverse experience of rash, which progressed from mild/moderate to serious in one subject and only six subjects completed the PK study.

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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. Raltegravir does not affect CYP enzymes.

Coadministration with a desogestrel-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possible CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4. Raltegravir had no significant effect on ethinylestradiol pharmacokinetics when coadministered with a triphasic COC containing ethinylestradiol/norgestimate.

Coadministration with a desogestrel-containing progestogen-only pill (POP) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Desogestrel is a prodrug which is activated to etonogestrel by CYP2C9 (and possible CYP2C19); the metabolism of etonogestrel is mediated by CYP3A4.

Coadministration has not been studied. Diamorphine is rapidly metabolized by sequential deacetylation to morphine which is then mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Raltegravir is not expected to affect the pharmacokinetics of drugs that are substrates of UGT1A1, UGT2B7 or P-glycoprotein (e.g., opioid analgesics).

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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Raltegravir is not expected to affect the pharmacokinetics of opioid analgesics.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Dipyridamole is glucuronidated by many UGTs, specifically those of the UGT1A subfamily. Raltegravir does not inhibit or induce these UGTs.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as dofetilide is mainly excreted unchanged in urine.

Triumeq (dolutegravir, abacavir, lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. If intensification of HIV treatment is needed, alternatives to raltegravir should be considered as coadministering two integrase inhibitors (i.e., raltegravir and dolutegravir) is unlikely to be of clinical benefit.

Dovato (dolutegravir/lamivudine) is indicated for use as a complete regimen for the treatment of HIV-1 infection. If intensification of HIV treatment is needed, alternatives to raltegravir should be considered as coadministering two integrase inhibitors (i.e., raltegravir and dolutegravir) is unlikely to be of clinical benefit.

Juluca (dolutegravir/rilpivirine) is indicated for use as a complete regimen for the treatment of HIV-1 infection and should not be administered with other antiretroviral products. If intensification of HIV treatment is needed, alternatives to raltegravir should be considered as coadministering two integrase inhibitors (i.e., raltegravir and dolutegravir is unlikely to be of clinical benefit.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs there is little potential for interaction. 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 co-administered with antiretrovirals.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doravirine is metabolized by CYP3A4; raltegravir is metabolized by UGT1A1. Neither drug has any inhibitory or inducing effects on P450 or UGT enzymes, therefore no significant interactions are expected between doravirine and raltegravir.

Delstrigo (doravirine, 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 raltegravir would be possible from a pharmacokinetic standpoint. Coadministration of raltegravir and doravirine has not been studied, but a clinically significant interaction is unlikely. In drug interaction studies, raltegravir (400 mg twice daily) did not have a clinically meaningful effect on the pharmacokinetics of lamivudine. Coadministration of raltegravir (400 mg twice daily) and tenofovir-DF increased raltegravir AUC (49%) and Cmax (64%), but had no effect on Cmin; tenofovir AUC, Cmax and Cmin decreased by 10%, 23% and 13%, respectively. The increase in raltegravir exposure does not require any dose adjustment.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Doxorubicin is mainly eliminated in the bile by P-gp and BCRP and does not undergo CYP-mediated metabolism. (Some product labels suggest doxorubicin is a substrate of CYP3A4, however, there are no strong data supporting the role of CYP3A4 in doxorubicin metabolism.)

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. No significant metabolism of doxycycline occurs, it is cleared intact by renal and biliary mechanisms.

Coadministration with a drospirenone-containing combined oral contraceptive (COC) has not been studied. Drospirenone is metabolized to a minor extent via CYP3A4. Ethinylestradiol is mainly metabolized by hydroxylation. Raltegravir does not interact with these metabolic pathways.

Coadministration with drospirenone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Drospirenone is metabolized to a minor extent via CYP3A4. Raltegravir does not interact with this metabolic pathway. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as dulaglutide is presumed to be degraded by general protein catabolism pathways. Dulaglutide delays gastric emptying and has the potential to impact the rate of absorption of concomitantly administered oral medicinal products. However, interaction studies did not result in any clinically relevant effects and no dose adjustment of comedications is recommended.

Coadministration with dydrogesterone as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Dydrogesterone is metabolized to dihydrodydrogesterone (possibly via CYP3A4). Raltegravir does not interact with this metabolic pathway. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Edoxaban is a substrate for P-gp but raltegravir does not inhibit or induce P-gp.

No dose adjustment is required when efavirenz is coadministered with twice daily or once daily raltegravir. Efavirenz (600 mg once daily) did not have a clinically meaningful effect on the pharmacokinetics of raltegravir. Coadministration with raltegravir (400 mg single dose) decreased raltegravir AUC, C12 and Cmax by 36%, 21% and 36%, respectively. Coadministration with raltegravir (1,200 mg single dose) decreased raltegravir AUC, C24 and Cmax by 14%, 6% and 9%, respectively.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Eflornithine is predominantly eliminated unchanged via the kidneys.

Coadministration with elbasvir/grazoprevir has not been studied. Coadministration of multiple doses of elbasvir with a single dose of raltegravir had no significant effect the pharmacokinetics of raltegravir. Coadministration of multiple doses of grazoprevir and raltegravir increased raltegravir AUC by 43% (which is not considered clinically relevant for raltegravir). Raltegravir had no significant effect on the pharmacokinetics of grazoprevir and elbasvir. No dose adjustments are required.

Genvoya (elvitegravir, cobicistat, emtricitabine, tenofovir alafenamide) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., raltegravir and elvitegravir) is unlikely to be of clinical benefit.

Stribild (elvitegravir, cobicistat, emtricitabine, tenofovir-DF) is indicated for use as a complete regimen for the treatment of HIV 1 infection and must not be administered with other antiretroviral products. Furthermore, coadministering two integrase inhibitors (i.e., raltegravir and elvitegravir) is unlikely to be of clinical benefit.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Empagliflozin is mainly glucuronidated by UGTs 1A3, 1A8, 1A9 and 2B7. It is a substrate of P-gp and BCRP, and also a substrate of the renal transporter OAT3 and the hepatic transporters OATP1B1 and OATP1B3. Raltegravir is unlikely to affect the metabolism of empagliflozin and empagliflozin is unlikely to affect raltegravir concentrations as it does not inhibit or induce CYPs and does not inhibit UGTs. 

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

Coadministration had not been studied. Tenofovir alafenamide exposure is not expected to be affected by raltegravir nor is it expected to affect the metabolic and excretion pathways relevant to raltegravir. The recommended dose of Descovy for HIV-1 treatment is 200/25 mg once daily.

Coadministration with twice daily raltegravir has not been studied. Population PK analysis showed emtricitabine/tenofovir-DF had minimal effect on the pharmacokinetics of once daily raltegravir (12% increase in relative bioavailability). Coadministration of tenofovir-DF and raltegravir (400 mg twice daily) increased raltegravir AUC (49%) and Cmax (64%), but had no effect on Cmin; tenofovir AUC, Cmax and Cmin decreased by 10%, 23% and 13%, respectively. The safety profile observed in patients who used atazanavir and/or tenofovir-DF (both agents that increase raltegravir concentrations) was generally similar to that of patients who did not use these agents. No clinically significant interaction is expected with emtricitabine. No dose adjustment is required when coadministered with twice daily or once daily raltegravir.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Ephedrine is predominantly eliminated unchanged via the kidneys.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Eplerenone is metabolized by CYP3A4 but raltegravir does not inhibit or induce CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Epoprostenol is rapidly hydrolyzed in the blood.

Coadministration has not been studied. Erythromycin is considered to be a moderate inhibitor of CYP3A4 but a clinically significant interaction is not expected as raltegravir is metabolised by UGT1A1.

Coadministration has not been studied. Eslicarbazepine is partly eliminated unchanged renally and partly glucuronidated by UGT2B4. Eslicarbazepine is a weak/moderate inducer and therefore may decrease raltegravir concentrations due to induction of UGT1A1. Closely monitor virological response and monitor raltegravir plasma concentrations (when possible). Consider use of other anticonvulsants.

Coadministration has not been studied but a clinically significant interaction is not expected. Coadministration of omeprazole and raltegravir (400 mg twice daily) increased raltegravir AUC, Cmax and C12h by 37%, 51% and 24%. Population PK analysis showed that the effect of gastric pH altering agents on the pharmacokinetics of once daily raltegravir was minimal (~9% decrease in relative bioavailability), and was not statistically or clinically significant. Concomitant use of raltegravir with proton pump inhibitors and H2 blockers did not result in a unique safety signal in Phase 3 studies. No dose adjustment is required with twice daily or once daily raltegravir.

Coadministration with estradiol as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Estradiol is metabolized by CYP3A4, CYP1A2 and is glucuronidated. Raltegravir does not interact with these metabolic pathways. Preliminary data with estradiol administered as feminizing hormone therapy (FHT) to trans women with HIV taking FHT and integrase inhibitors (bictegravir/emtricitabine/tenofovir alafenamide, n=8; dolutegravir/abacavir/lamivudine, n=2) suggest a low probability of clinically relevant drug-drug interactions between FHT and unboosted integrase inhibitor-based ART.

Coadministration of raltegravir and a triphasic oral contraceptive containing ethinylestradiol and norgestimate had no significant effect on ethinylestradiol pharmacokinetics. Exposure of norelgestromin (the active metabolite of norgestimate) increased by 14% (AUC), 29% (Cmax) and 10% (Cmin). The effects are not considered to be clinically important and no dose adjustment is required for oral contraceptives containing ethinylestradiol and norgestimate when coadministered with twice daily or once daily raltegravir. Note, use of ethinylestradiol as part of gender affirming treatment is not recommended due to thrombotic risks.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Ethionamide is extensively metabolized in the liver, animal studies suggest involvement of flavin-containing monooxygenases.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etidocaine is metabolized by CYP3A4, but raltegravir does not inhibit or induce drug metabolizing enzymes.

Coadministration with an etonogestrel-containing progestogen-only implant has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolized by CYP3A4. Raltegravir does not interact with this metabolic pathway.

Coadministration with etonogestrel as a combined vaginal ring (CVR) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Etonogestrel is metabolized by CYP3A4. Ethinylestradiol is mainly metabolized by hydroxylation. Raltegravir does not interact with these metabolic pathways and had no significant effect on ethinylestradiol pharmacokinetics when coadministered with a triphasic COC containing ethinylestradiol/norgestimate.

No dose adjustment needed for either drug when coadministered with twice daily raltegravir. Coadministration with twice daily raltegravir increased etravirine Cmax (4%), AUC (10%) and Cmin (17%) and decreased raltegravir Cmax (11%), AUC (10%) and Cmin (34%). When etravirine was added to raltegravir/darunavir/ritonavir, raltegravir AUC, Cmax and Cmin increased by 29%, 21% and 54%, respectively and darunavir AUC, Cmax and Cmin increased by 14%, 6%, and 29%, respectively. The European product label for raltegravir states that no dose adjustment is required with once daily raltegravir, however, the US product label does not recommend coadministration of etravirine with once daily raltegravir.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. There is no evidence to suggest that eucalyptus impacts UGTs.

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

Coadministration of famotidine and twice daily raltegravir (400 mg twice daily) increased raltegravir AUC, Cmax and C12h by 44%, 60% and 6%. Population PK analysis showed that the effect of gastric pH altering agents on the pharmacokinetics of once daily raltegravir was minimal (~9% decrease in relative bioavailability), and was not statistically or clinically significant. Concomitant use of raltegravir with proton pump inhibitors and H2 blockers did not result in a unique safety signal in Phase 3 studies. No dose adjustment is required with twice daily or once daily raltegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Raltegravir is not expected to affect the pharmacokinetics of opioid analgesics.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fesoterodine is rapidly hydrolysed to its active metabolite which is subsequently metabolized by CYP2D6 and CYP3A4.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flucloxacillin is mainly eliminated renally partly by glomerular filtration and partly by active secretion via OAT1. Flucloxacillin is thought to be a weak inducer of CYP3A4 particularly at higher doses (>2-3 g daily), however, no significant interactions were observed with other inducers (efavirenz, rifabutin) and therefore flucloxacillin may be used with the recommended dose of raltegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Raltegravir is not expected to affect the pharmacokinetics of azole antifungals.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Flunisolide undergoes CYP3A4-mediated metabolism. Raltegravir does not interact with flunisolide metabolism.

Coadministration has not been studied but based on metabolism and clearance a clinically relevant drug interaction is unlikely with the topical use of fluocinolone.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fluorouracil is metabolised via the same mechanisms as endogenous uracil, including via dihydropyrimidine dehydrogenase. There is therefore little potential for an interaction with raltegravir 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. Fluphenazine is metabolised by CYP2D6.

No dose modification of raltegravir required.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Raltegravir is not expected to affect the pharmacokinetics of statins.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Folic acid is metabolized to dihydrofolic acid and tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide and folate reductases.

Coadministration has not been studied. Folic acid is metabolized to dihydrofolic acid and tetrahydrofolic acid with the aid of reduced diphosphopyridine nucleotide and folate reductases. A pharmacokinetic interaction is unlikely with folic acid itself. However, folic acid may be administered in a multivitamin preparation which may also contain polyvalent cations. As the effect of cationic complexation cannot be excluded, caution is recommended as raltegravir concentrations may be reduced.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fondaparinux does not undergo cytochrome metabolism but is eliminated predominantly renally.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fosinopril is hydrolysed by esterases in the GI mucosa and liver.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely as gabapentin is cleared mainly by glomerular filtration.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Although garlic has been shown to induce intestinal CYP3A4 and/or P-gp, this is not expected to impact raltegravir exposure.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction. Gentamicin is predominantly eliminated unchanged via the kidneys.

Coadministration with a gestodene-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Gestodene is metabolized by CYP3A4 and to a lesser extent by CYP2C9 and CYP2C19. Ethinylestradiol is mainly metabolized by hydroxylation. Raltegravir does not interact with these metabolic pathways. Raltegravir had no significant effect on ethinylestradiol pharmacokinetics when coadministered with a triphasic COC containing ethinylestradiol/norgestimate.

Coadministration has not been studied but based on metabolism and clearance, a clinically significant interaction is unlikely. There is no evidence to suggest that ginger inhibits or induces UGTs.

Coadministration with glecaprevir/pibrentasvir increased raltegravir Cmax, AUC and Cmin by 34%, 47% and 164% (n=12), due to inhibition of UGT1A1. However this increase was within safety bounds and is not deemed clinically significant. Glecaprevir Cmax and AUC decreased by 6% and 7%, and Ctrough increased by 2%; pibrentasvir Cmax increased by 1%, and AUC and Ctrough decreased by 1% and 3%. No dose adjustment is required when glecaprevir/pibrentasvir is coadministered with raltegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glyceryl trinitrate is metabolised by aldehyde dehydrogenase-2. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Glycopyrronium bromide is mainly eliminated renally (active secretion via organic cation transporter) and is also partly hydroxylated via multiple CYPs. Inhibition or induction of its metabolism is unlikely to result in a significant change in exposure.

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

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

This interaction has not been studied. Griseofulvin undergoes glucuronidation, although this is not the sole route of metabolism. There is little potential for interactions via competition of griseofulvin with raltegravir for glucuronidation pathways. In vitro studies using rat liver microsomes have shown that griseofulvin can inhibit glucuronidation of some substances, however the UGT isoforms affected are not known. Potentially levels of raltegravir could be increased by griseofulvin, however due to lack of data, the significance is unknown.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Heparin is thought to be eliminated via the reticuloendothelial system.

Coadministration has not been studied but based on metabolism and clearance, a clinically relevant drug interaction is unlikely. When used illicitly, heroin is mainly injected or inhaled through the nose and goes directly in the bloodstream. Heroin is then rapidly deacetylated to 6-monoacetylmorhine (6-MAM) and subsequently to morphine by plasma and liver esterase, respectively. Morphine is mainly glucuronidated to morphine-3-glucuronide (UGT2B7>UGT1A1) and, to a lesser extent, to the pharmacologically active morphine-6-glucuronide (UGT2B7>UGT1A1). Raltegravir is not expected to affect the pharmacokinetics of drugs that are substrates of UGT1A1, UGT2B7 or P-glycoprotein (e.g., opioids).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. In vitro data indicate that extracts of hops activate PXR and thereby induce the expression of CYP3A4, CYP2B6 and MDR1 to a degree similar to that of St John's wort. However, a pharmacokinetic study with a standardised hop extract showed no clinically relevant effect on CYPs 2C9, 1A2, and 2D6 and suggested only minor induction of CYP3A4/5 (AUC of alprazolam, a CYP3A4/5 substrate, decreased by ~8%). No effect on raltegravir is expected as its metabolism is not CYP-mediated.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs there is little potential for interaction. Hydralazine is metabolised via primary oxidative metabolism and acetylation.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. Hydroxyurea undergoes metabolism via non-CYP mediated metabolism and is unlikely to affect concentrations of raltegravir.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No drug interaction studies have been conducted with ibalizumab: based on ibalizumab’s mechanism of action and target-mediated drug disposition, drug-drug interactions are not expected. Raltegravir undergoes hepatic metabolism whereas ibalizumab, a monoclonal antibody binding to the CD4 receptor, is likely to be eliminated via intracellular catabolism similarly to other monoclonal antibodies. Dose modifications of ibalizumab are not required when administered with any other antiretroviral.

Ibandronic acid should be taken after an overnight fast (at least 6 hours) and before the first food or drink of the day. Medicinal products and supplements should be similarly avoided prior to taking ibandronic acid. Fasting should be continued for at least 30 minutes after taking ibandronic acid.

This interaction has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for pharmacokinetic interaction. Ifosfamide is predominantly metabolized by CYP3A4 and CYP2B6.