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

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abemaciclib is metabolized by CYP3A4. Didanosine does not interact with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Abiraterone is metabolized by CYP3A4 and SULT2A1. Didanosine does not interact with these metabolic pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Acalabrutinib is metabolized by CYP3A4. Didanosine does not interact with this pathway.

Coadministration has not been studied. Acamprosate is eliminated unchanged in the urine both via glomerular filtration and active secretion (exact transporter unknown, possibly OATs or OCTs). Didanosine (a substrate of OAT1) and acamprosate may compete for tubular secretion, which could lead to increased levels of either drug. The clinical relevance of this interaction is unknown.

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. Acetazolamide is predominantly excreted unchanged via active renal tubular secretion. In vitro studies have shown that acetazolamide may competitively inhibit the renal transporters OAT1, OAT3 and OAT4. However, a clinically relevant interaction is unlikely in the range of observed clinical concentrations.

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 didanosine via modulation of, or competition for metabolic or elimination pathways.

Coadministration has not been studied but based on the metabolic data there is little potential for pharmacokinetic interactions.

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. Didanosine is mostly eliminated renally. 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 is contraindicated the US product label for didanosine and not recommended in the European product label as didanosine exposure is increased (AUC and Cmax increased by 105% and 71% with didanosine buffered tablets). Patients treated with didanosine who require allopurinol administration should be switched to an alternative treatment regimen.

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. Furthermore, alogliptin was shown to be neither a substrate nor an inhibitor of the renal transporters OAT1 or OAT3.

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. Didanosine 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.

Coadministration has not been studied. Renal clearance of ampicillin occurs partly by glomerular filtration and partly by tubular secretion. After oral administration, approximately 20-40% is excreted unchanged in the urine, whereas about 60-80% is excreted unchanged in the urine after parenteral administration. As didanosine is eliminated by renal tubular secretion, there is potential for competition with ampicillin for renal transporters, which could lead to increased levels of either drug when ampicillin is administered intravenously. When administered orally, there is little potential for significant interaction.

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 by CYP1A2, CYP2C8, CYP2C9 and CYP2C19.

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. Apremilast has no inhibitory or inducing effects or drug transporters. Didanosine does not interact with apremilast’s elimination pathways. 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 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.

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. There is therefore little potential for an interaction with didanosine 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 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. There is therefore little potential for interaction with didanosine 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.

Coadministration has not been studied but based on metabolism and clearance a pharmacokinetic interaction is unlikely. However, acute pancreatitis is a relatively common adverse event in patients taking asparaginase, and has also been associated with didanosine therapy (<1% of patients), which has been fatal in some cases. When treatment with other medicinal products known to cause pancreatic toxicity is unavoidable, didanosine should be used only with extreme caution and close observation is warranted.

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).

It is recommended that didanosine be administered on an empty stomach. When coadministered with didanosine, atazanavir/ritonavir should be given with food 2 h before or 1 h after didanosine. The buffered formulation of didanosine, but not the enteric coated formulation, decreased atazanavir concentrations. Didanosine concentrations were decreased in the presence of food.

It is recommended that didanosine be administered on an empty stomach. When coadministered with didanosine, atazanavir should be given with food 2 h before or 1 h after didanosine. The buffered formulation of didanosine, but not the enteric coated formulation, decreased atazanavir concentrations. Didanosine concentrations were decreased in the presence of food.

It is recommended that didanosine be administered on an empty stomach. When coadministered with didanosine, atazanavir/cobicistat should be given with food 2 h before or 1 h after didanosine. The buffered formulation of didanosine, but not the enteric coated formulation, decreased atazanavir concentrations. Didanosine concentrations were decreased in the presence of food.

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. Atomoxetine is metabolized by CYP2D6.

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 didanosine 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. 

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 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. 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Bazedoxifene is glucuronidated by UGT1A1/8/10 and conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Didanosine does not interact with these metabolic pathways.

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. In vitro data indicate that bendroflumethiazide inhibits these renal transporters but a clinically relevant drug interaction is unlikely in the range of observed clinical concentrations.

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.

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 as betrixaban is largely eliminated unchanged through biliary secretion via 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, increased didanosine concentrations and toxicity were observed when combined with tenofovir-DF. A similar effect with tenofovir alafenamide cannot be excluded.

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.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. The metabolic pathway of blinatumomab has not been characterized. Like other protein therapeutics, blinatumomab is expected to be degraded into small peptides and amino acids via catabolic pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Bosutinib is metabolized by CYP3A4. Didanosine does not interact with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. 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 didanosine. MMAE is a substrate of CYP3A4 and P-gp but didanosine does not interfere with these pathways. 

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 with brincidofovir has not been studied. Brincidofovir is a prodrug converted to cidofovir. Coadministration of cidofovir/probenecid increased didanosine AUC by 1.6-fold. There was no effect on cidofovir pharmacokinetics.

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.

The interaction between buprenorphine and didanosine was investigated in 10 HIV-negative, buprenorphine/naloxone maintained subjects. When compared to values obtained from control subjects not receiving buprenorphine, no significant changes in buprenorphine pharmacokinetics were observed. When compared to controls, buprenorphine had no statistically significant effect on NRTI concentrations.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabazitaxel is metabolized by CYP3A4. Didanosine does not interact with this pathway.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabergoline is extensively metabolized by the liver predominantly via hydrolysis (non-CYP mediated metabolism).

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Cabergoline is extensively metabolized by the liver predominantly via hydrolysis (non-CYP mediated metabolism).

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

Cabenuva (cabotegravir LA, rilpivirine LA) is indicated for use as complete regimens 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 didanosine should be considered. 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 based on metabolism and clearance a clinically significant interaction is unlikely. Cabozantinib is metabolized by CYP3A4. Didanosine does not interact with this pathway.

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. Didanosine 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 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 didanosine.

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.

Coadministration has not been studied. Capecitabine is activated by sequential enzyme reactions to fluorouracil. Dihydropyrimidine dehydrogenase plays a role in fluorouracil metabolism. Nucleoside analogues such as didanosine may compete for these metabolic pathways. The clinical relevance of this interaction is unknown.

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. However, coadministration can increase the risk of peripheral neuropathy due to additive toxicity.

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 didanosine does not undergo CYP3A4 metabolism.

Coadministration has not been studied. Cefalexin is predominantly eliminated unchanged renally by glomerular filtration and tubular secretion via OAT1 and MATE1. Thus, there is potential for competition with cefalexin for renal transporters, which could lead to increased concentrations of either drug.

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 metabolised via UDP-glucuronyltransferases, in particular UGT2B7.

Coadministration with a chlormadinone-containing combined oral contraceptive (COC) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Chlormadinone undergoes extensive hepatic metabolism by hydroxylation (likely CYP mediated). Ethinylestradiol is also metabolized by hydroxylation and glucuronidation. Didanosine does not interact with these metabolic pathways.

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.

No interaction is expected with Videx-EC (didanosine gastro-resistant capsules). However, didanosine chewable/dispersible tablets and powder for oral solution contain an antacid which reduces chlorpromazine absorption. Chlorpromazine should not be taken within 2 hours of antacid administration.

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.

Coadministration of didanosine gastro-resistant capsules had no effect on ciprofloxacin AUC or Cmax. 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.

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.

Coadminisistration has not been studied. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction with clofazimine and enteric coated formulations of didanosine. Coadministration of the buffered formulations of didanosine may decrease clofazimine exposure. In a crossover study in 16 healthy volunteers, administration with an aluminium-magnesium antacid decreased clofazimine bioavailability by 22%.

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. 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 an interaction with didanosine 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 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. There is little potential for interaction with didanosine via modulation of, or competition for, metabolic pathways.

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 didanosine, but for any medication taken with colestyramine.]

Coadministration with conjugated estrogens as hormone replacement therapy (HRT) has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Conjugated estrogens are metabolized by CYP3A4, CYP1A2 and are glucuronidated. Didanosine does not interact with these metabolic pathways. In addition, no interaction is expected with progestogens administered as part of HRT. 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 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. 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.

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 didanosine.

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

Coadministration with didanosine gastro-resistant capsules has not been studied. Coadministration of didanosine buffered tablets had no significant effect on dapsone AUC or Cmax. However, coadministration of both drugs may increase the risk of peripheral neuropathy (additive toxicity).

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

No significant interactions were observed when didanosine and darunavir/ritonavir were administered 2 h apart (didanosine on an empty stomach, 2 h prior to darunavir/ritonavir with food). No dose adjustments are required; however, as didanosine should be administered on an empty stomach it should be administered 1 h before or 2 h after darunavir/ritonavir (which are administered with food).

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, increased didanosine concentrations and toxicity has been observed when didanosine and tenofovir-DF are coadministered. A similar effect with tenofovir alafenamide cannot be excluded.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. No dose adjustments are required; however, as didanosine should be administered on an empty stomach it should be administered 1 h before or 2 h after darunavir/cobicistat (which are administered with food). 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. A clinical study reported that antiretroviral regimens containing didanosine had no effect on the pharmacokinetics of liposomal daunorubicin.

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. Didanosine 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. Ethinylestradiol is mainly metabolized by hydroxylation.

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 but based on metabolism and clearance a clinically significant interaction is unlikely. Dexlansoprazole is mainly metabolized by CYP2C19 (major) and CYP3A4 (minor).

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 didanosine.

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.

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 didanosine should be considered. The bioavailability of lamivudine has been shown to be significantly reduced in a dose dependent manner by sorbitol which is present in drug formulations such as didanosine chewable/dispersible tablet.

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 didanosine should be considered. The bioavailability of lamivudine has been shown to be significantly reduced in a dose dependent manner by sorbitol which is present in drug formulations such as didanosine chewable/dispersible tablet.

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 didanosine should be considered. 

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Donepezil is metabolized by CYP3A4 and to a lesser extent by CYP2D6. Didanosine does not interact with this metabolic pathway.

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. Didanosine does not interfere with CYP450 mediated metabolism.

Delstrigo (doravirine, lamivudine, 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, increased didanosine concentrations and toxicity has been observed when didanosine and tenofovir-DF are coadministered. In addition, the bioavailability of lamivudine has been shown to be significantly reduced in a dose dependent manner by sorbitol which is present in drug formulations such as didanosine chewable/dispersible tablet.

This interaction has not been studied. Antacids may impair absorption of doxycycline and administration of antacids should be maximally separated from doses of doxycycline. This interaction relates only to buffered tablet formulations of didanosine, which contain antacids. Based on the metabolism/elimination and toxicity profiles of both drugs, there is little potential for interaction between doxycycline and enteric coated formulations of didanosine.

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. Didanosine 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. Didanosine does not interact with this metabolic pathway. In addition, no interaction is expected with estradiol or estrogens administered as part of HRT.

Coadministration with a drospirenone progestogen-only pill (POP) 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. Didanosine does not interact with this metabolic pathway.

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). Didanosine 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 minimally metabolised by hydrolysis (mediated by carboxylesterase 1), conjugation, or oxidation by CYP3A4/5 (<10%). Edoxaban is eliminated primarily as unchanged drug in urine.

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 has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Didanosine is phosphorylated to its active triphosphate form and is not a substrate of any CYP isoenzyme. It is renally excreted.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eletriptan is metabolised by CYP3A4 and does not induce or inhibit CYPs.

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, increased didanosine concentrations and toxicity were observed when combined with tenofovir-DF. A similar effect with tenofovir alafenamide cannot be excluded.

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, increased didanosine concentrations and toxicity were observed when combined with tenofovir-DF.

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. 

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

Coadministration has not been studied. Increased didanosine concentrations and toxicity were observed when combined with tenofovir-DF. A similar effect with tenofovir alafenamide cannot be excluded. If this combination is judged strictly necessary, patients should be carefully monitored for efficacy and didanosine related adverse events.

Emtricitabine and tenofovir alafenamide used as PrEP are not expected to be coadministered with antiretrovirals. Coadministration has not been studied. Increased didanosine concentrations and toxicity were observed when combined with tenofovir-DF. A similar effect with tenofovir alafenamide cannot be excluded. If this combination is judged strictly necessary, patients should be carefully monitored for efficacy and didanosine related adverse events.

Coadministration is not recommended in the European product label due to increased didanosine concentrations (40-60% increase in systemic exposure) and toxicity. The US product label for emtricitabine/tenofovir-DF recommends close monitoring for didanosine-associated adverse events and a reduced dose of didanosine (250 mg once daily for adults weighing 60 kg or greater with creatinine clearance 60 mL/min or greater; 200 mg once daily for adults weighing less than 60 kg with creatinine clearance 60 mL/min or greater). However, a decreased dosage of 250 mg didanosine with tenofovir-DF has been associated with reports of high rates of virological failure within several tested combinations. Coadministration with emtricitabine has not been studied. There have been reports of a high rate of virological failure and of emergence of resistance at early stage when tenofovir-DF was combined with lamivudine and didanosine as a once daily regimen. A similar outcome would be expected if emtricitabine/tenofovir-DF was combined with a third NRTI.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Enzalutamide is primarily metabolized by CYP2C8. 

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 clinically significant interaction is unlikely as eplerenone is mainly metabolized by 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Erythromycin is extensively metabolized in the liver.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Eslicarbazepine is partly eliminated unchanged renally and partly glucuronidated by UGT2B4.

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. Didanosine does not interact with these metabolic pathways.

Coadministration has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Ethinylestradiol is mainly metabolized by hydroxylation. 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 as etidocaine is metabolized by CYP3A4.

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. Didanosine 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. Didanosine does not interact with these metabolic pathways.

Coadministration with didanosine gastro-resistant capsules has not been studied. Coadministration with didanosine buffered tablets increased etravirine Cmax, AUC and Cmin by 16%, 11% and 5%, respectively; didanosine Cmax decreased by 9% and there was no change in AUC. No dose adjustment is needed for either drug. 

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 or P-gp.

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 has not been studied but based on metabolism and clearance a clinically significant interaction is unlikely. Fampridine is metabolized by CYP2E1 but is predominantly eliminated unchanged by the kidney with active secretion by OCT2. Didanosine does not interfere with fampridine elimination pathway.

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. 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. Filgrastim is eliminated mainly by neutrophil-mediated clearance and renal excretion.

No significant interaction was observed following coadministration of fluconazole and didanosine gastro-resistant capsules.

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

Coadministration has not been studied. Fluorouracil is metabolised via the same mechanisms as endogenous uracil, including via dihydropyrimidine dehydrogenase. Nucleoside analogues such as didanosine may compete for this metabolic pathway. The clinical relevance of this interaction is unknown.

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

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. 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 but based on metabolism and clearance a clinically significant interaction is unlikely when folic acid is administered in a multivitamin preparation. 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 but based on metabolism and clearance a clinically significant interaction is unlikely. Fondaparinux does not undergo cytochrome metabolism but is eliminated predominantly renally.

No pharmacokinetic interaction was observed when didanosine and foscarnet were coadministered.

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. Fostemsavir is a prodrug and is hydrolysed to the active compound temsavir in the small intestine. Temsavir is mainly metabolized by esterase-mediated hydrolysis with a small contribution of CYP3A4. Didanosine does not interfere with fostemsavir metabolic pathway.