Lamivudine and zidovudine interactions

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals [See Warnings and Precautions (5. (Adefovir label, Boxed warning)

Because BIXLENVO is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended ( 7.1 ) (Bictegravir, emtricitabine, and tenofovir alafenamide label, Drug interactions)

Coadministration with other antiretroviral medications for PrEP is not recommended. (Cabotegravir label, Drug interactions)

Antiviral and antiretroviral drugs: Avoid concomitant use. (Cladribine label, Drug interactions)

PREZCOBIX or PREZCOBIX PED is not recommended in combination with other antiretroviral drugs that require pharmacokinetic boosting. (Darunavir and cobicistat label, Warnings and precautions)

Lactic Acidosis and Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs and other antiretrovirals. (Efavirenz, lamivudine, and tenofovir label, Warnings and precautions)

GENVOYA should not be administered with other antiretroviral medications for treatment of HIV-1 infection. (Elvitegravir, cobicistat, emtricitabine, and tenofovir label, Drug interactions)

Lactic Acidosis/Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including FTC, alone or in combination with other antiretrovirals. (Emtricitabine label, Warnings and precautions)

COMPLERA is a complete regimen for the treatment of HIV-1 infection; therefore, coadministration with other antiretroviral medications for treatment of HIV-1 infection is not recommended. (Emtricitabine, rilpivirine, and tenofovir label, Drug interactions)

Therapy with BARACLUDE is not recommended for HIV/HBV co-infected patients who are not also receiving highly active antiretroviral therapy (HAART) [see Warnings and Precautions (5.2) ] . (Entecavir label, Boxed warning)

…Nucleoside analogues, e.g., ribavirin Hematologic/Bone Marrow Suppressive/Cytotoxic Agents Coadministration with the following drugs may increase the hematologic toxicity of zidovudine: • Ganciclovir • Interferon alfa • Ribavirin • Other bone marrow suppressive or cytotoxic agents 7.2 Lamivudine Sorbitol Coadministration of single doses of lamivudine and sorbitol resulted… (Lamivudine and zidovudine label, Drug interactions)

Increased Toxicity with Concomitant Use of Antiretroviral Drugs Pancreatitis Pancreatitis (including fatal cases) have occurred in patients with HIV infection during therapy with hydroxyurea and didanosine, with or without stavudine. (Hydroxyurea label, Drug interactions)

Consider alternative HCV or antiretroviral therapy to avoid increases in tenofovir exposures. (Ledipasvir and sofosbuvir label, Drug interactions)

Female gender and higher CD4 + cell counts at initiation of therapy place patients at increased risk; women with CD4 + cell counts greater than 250 cells/mm 3 , including pregnant women receiving nevirapine in combination with other antiretrovirals for the treatment of HIV-1 infection, are at the greatest risk. (Nevirapine label, Boxed warning)

• Hepatic decompensation, some fatal, has occurred in HIV‑1/HCV co‑infected patients receiving combination antiretroviral therapy and interferon alfa with/without ribavirin. (Lamivudine and zidovudine label, Warnings and precautions)

Therefore, co-administration with antiretroviral and anti-HCV drugs metabolized by CYP3A is not recommended or there may be a need to increase the dose of antiretroviral or anti-HCV drugs (see PRECAUTIONS-Drug Interactions ). (Rifabutin label, Warnings)

…Concentrations Administered with rifampin 600 mg daily, unless otherwise specified AUC = area under the time-concentration curve Drug or Drug Class and Prevention or Management Clinical Effect Antiretrovirals Prevention or Management: Concomitant use is contraindicated (see CONTRAINDICATIONS ) Atazanavir Decrease AUC by 72% Darunavir Rifampin dosage used concomitantly with… (Rifampin label, Drug interactions)

St. John's wort can lower blood levels of some HIV medicines enough to cause treatment failure. (NCCIH, St. John's Wort)

Lactic Acidosis/Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including TDF, alone or in combination with other antiretrovirals. (Tenofovir label, Warnings and precautions)

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including zidovudine and other antiretrovirals. (Zidovudine label, Boxed warning)

Riociguat Coadministration with fixed-dose abacavir/dolutegravir/lamivudine resulted in increased riociguat exposure, which may increase the risk of riociguat adverse reactions [see Clinical Pharmacology ( 12.3 )] . (Abacavir label, Drug interactions)

Antiretrovirals: Patients who are on chronic buprenorphine treatment should have their dose monitored if NNRTIs are added to their treatment regimen. (Buprenorphine and naloxone label, Drug interactions)

Monitor patients for increased toxicity when MRP2 inhibitors (e.g., abacavir, adefovir, cidofovir, furosemide, lamivudine, nevirapine, ritonavir, probenecid, saquinavir, and tenofovir) are co-administered with COMETRIQ [see Clinical Pharmacology ( 12.3 )] . (Cabozantinib label, Drug interactions)

Zidovudine should either be temporarily discontinued or decreased by 50% when coadministered with probenecid on the day of cidofovir infusion. (Cidofovir label, Drug interactions)

Zidovudine Zidovudine: Simultaneous oral administration of clarithromycin immediate-release tablets and zidovudine to HIV-infected adult patients may result in decreased steady-state zidovudine concentrations. (Clarithromycin label, Drug interactions)

…can cause leukopenia. ● Natalizumab ● Paclitaxel: Increased hematotoxicity has been reported when cyclophosphamide was administered after paclitaxel infusion. ● Thiazide diuretics ● Zidovudine Increased cardiotoxicity ● Anthracyclines ● Cytarabine ● Pentostatin ● Radiation therapy of the cardiac region ● Trastuzumab Increased pulmonary toxicity ● Amiodarone ● G-CSF,… (Cyclophosphamide label, Drug interactions)

Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with dexlansoprazole may reduce antiviral effect and promote the development of drug resistance . (Dexlansoprazole label, Drug interactions)

Dosage adjustment of amitriptyline/nortriptyline, propofol, warfarin, and zidovudine may be necessary if used concomitantly with Depakote ER ( 7.2 ) (Divalproex (valproate) label, Drug interactions)

…dolutegravir exposures observed in INSTI-experienced patients (with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance [see Microbiology ( 12.4 )] ) upon coadministration with certain inducers may result in loss of therapeutic effect and development of resistance to TIVICAY or other coadministered antiretroviral agents. (Dolutegravir label, Drug interactions)

Examples: cyclosporine, gemfibrozil, antiretrovirals (atazanavir, lopinavir, ritonavir, saquinavir, tipranavir), rifampin, eltrombopag Drugs that Cause Constipation Clinical Impact: Increased risk for constipation related adverse reactions and potential for constipation related serious adverse reactions Intervention: Avoid use with other drugs that may cause… (Eluxadoline label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with esomeprazole may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ] . (Esomeprazole label, Drug interactions)

(See CLINICAL PHARMACOLOGY: Drug Interaction Studies . ) Zidovudine Fluconazole increases the C max and AUC of zidovudine by 84% and 74%, respectively, due to an approximately 45% decrease in oral zidovudine clearance. (Fluconazole label, Drug interactions)

Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with lansoprazole may reduce antiviral effect and promote the development of drug resistance. (Lansoprazole label, Drug interactions)

In patients taking ARAVA, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. (Leflunomide label, Drug interactions)

Zidovudine Experimental evidence demonstrated that methadone increased the AUC of zidovudine which could result in toxic effects. (Methadone label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with esomeprazole magnesium may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology (12.3) ]. (Naproxen and esomeprazole label, Drug interactions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir and nelfinavir) when used concomitantly with omeprazole may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology ( 12.3 )]. (Omeprazole label, Drug interactions)

Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir and nelfinavir) when used concomitantly with omeprazole may reduce antiviral effect and promote the development of drug resistance [see Clinical Pharmacology ( 12.3 )] . (Omeprazole and sodium bicarbonate label, Drug interactions)

Drug Interactions and Decreased Vitamin Absorption ORLISTAT may interact with concomitant drugs including cyclosporine, levothyroxine, warfarin, amiodarone, antiepileptic drugs, and antiretroviral drugs [see Drug Interactions (7) ]. (Orlistat label, Warnings and precautions)

• Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with pantoprazole may reduce antiviral effect and promote the development of drug resistance. (Pantoprazole label, Drug interactions)

Anti-HIV Drugs that are CYP3A4 Substrates Mechanism and Clinical Effect(s) Ritonavir and atazanavir are CYP3A4 substrates and posaconazole increased plasma concentrations of these drugs [see Clinical Pharmacology (12.3) ]. (Posaconazole label, Drug interactions)

However, the concomitant use of other antifolic drugs or agents associated with myelosuppression including sulfonamides or trimethoprim- sulfamethoxazole combinations, proguanil, zidovudine, or cytostatic agents (e.g., methotrexate), while the patient is receiving pyrimethamine, may increase the risk of bone marrow suppression. (Pyrimethamine label, Drug interactions)

Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir, and nelfinavir) when used concomitantly with rabeprazole may reduce antiviral effect and promote the development of drug resistance. (Rabeprazole label, Drug interactions)

Fixed-Dose Combination of Efavirenz, Emtricitabine, and Tenofovir Once-weekly coadministration of 900 mg PRIFTIN with the antiretroviral fixed-dose combination of efavirenz 600 mg, emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg in HIV-infected patients did not result in any substantial change in steady state exposures of efavirenz, emtricitabine,… (Rifapentine label, Drug interactions)

Hepatotoxicity Hepatic transaminase elevations exceeding 5 times the upper limit of normal, clinical hepatitis, and jaundice have occurred in patients receiving NORVIR alone or in combination with other antiretroviral drugs (see Table 2). (Ritonavir label, Warnings and precautions)

The influence of terbinafine on the pharmacokinetics of fluconazole, cotrimoxazole (trimethoprim and sulfamethoxazole), zidovudine or theophylline was not considered to be clinically significant. (Terbinafine label, Drug interactions)

In patients taking AUBAGIO, exposure of drugs which are OAT3 substrates (e.g., cefaclor, cimetidine, ciprofloxacin, penicillin G, ketoprofen, furosemide, methotrexate, zidovudine) may be increased. (Teriflunomide label, Drug interactions)

…myelosuppression or nephrotoxicity (e.g., adriamycin, dapsone, doxorubicin, flucytosine, hydroxyurea, pentamidine, tacrolimus, trimethoprim/ sulfamethoxazole, vinblastine, vincristine, and zidovudine) Unknown Because of potential for higher toxicity, coadministration with valganciclovir hydrochloride should be considered only if the potential benefits are judged to outweigh… (Valganciclovir label, Drug interactions)

Dosage adjustment of amitriptyline/nortriptyline, propofol, warfarin, and zidovudine may be necessary if used concomitantly with valproic acid oral solution (7.2) (Valproic acid label, Drug interactions)

Intervention: None Antiretrovirals: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Clinical Impact: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are metabolized principally by CYP3A4. (Buprenorphine label, Drug interactions)

Analysis of long-term data from Study 006 (median follow-up 180 weeks, 102 weeks, and 76 weeks for patients treated with efavirenz + zidovudine + lamivudine, efavirenz + indinavir, and indinavir + zidovudine + lamivudine, respectively) showed that, beyond 24 weeks of therapy, the incidences of new-onset nervous system symptoms among efavirenz-treated patients… (Efavirenz label, Warnings and precautions)

Lactic Acidosis/Severe Hepatomegaly with Steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including emtricitabine, a component of DESCOVY, and tenofovir DF, another prodrug of tenofovir, alone or in combination with other antiretrovirals. (Emtricitabine and tenofovir label, Warnings and precautions)

Stevens-Johnson syndrome was reported in 1.1% (2/177) of pediatric patients less than 18 years of age receiving Etravirine in combination with other HIV-1 antiretroviral agents in an observational study. (Etravirine label, Warnings and precautions)

Examples: Anti-fungals: itraconazole, posaconazole, voriconazole Antibiotics: erythromycin and clarithromycin Antiretrovirals: ritonavir Grapefruit juice CYP3A4 Inducers Clinical Impact: Hydrocortisone is metabolized by cytochrome P450 3A4 (CYP3A4). (Hydrocortisone label, Drug interactions)

Nucleoside Reverse Transcriptase Inhibitors: abacavir zidovudine ↓ abacavir ↓ zidovudine The clinical significance of this potential interaction is unknown. (Lopinavir and ritonavir label, Drug interactions)

Anti-HIV efavirenz, maraviroc, nevirapine, zidovudine, bictegravir/ emtricitabine/ tenofovir ↑ efavirenz ↑ maraviroc ↑ nevirapine ↓ zidovudine ↑ bictegravir ↔ emtricitabine ↑ tenofovir For further information, refer to the respective anti-HIV drugs prescribing information. (Nirmatrelvir and ritonavir label, Drug interactions)

Drug Interactions While specific studies on drug interactions with Pentamidine Isethionate have not been conducted, the majority of patients in clinical trials received concomitant medications, including zidovudine, with no reported interactions. (Pentamidine label, Drug interactions)

Antiretrovirals: atazanavir lopinavir ↑ voxilaprevir Coadministration of VOSEVI with atazanavir- or lopinavir-containing regimens is not recommended. tipranavir/ritonavir ↓ sofosbuvir ↓ velpatasvir Coadministration is not recommended. (Sofosbuvir and velpatasvir label, Drug interactions)

Drugs with No Observed Interactions with REYATAZ No clinically significant drug interactions were observed when REYATAZ was coadministered with methadone, fluconazole, acetaminophen, atenolol, or the nucleoside reverse transcriptase inhibitors lamivudine or zidovudine [see Clinical Pharmacology, Tables 21 and 22 (12.3) ] . (Atazanavir label, Drug interactions)

…PREZISTA/ritonavir is co-administered with the following medications: atazanavir, dolutegravir, efavirenz, etravirine, nevirapine, nucleoside reverse transcriptase inhibitors (abacavir, emtricitabine, emtricitabine/tenofovir alafenamide, lamivudine, stavudine, tenofovir disoproxil fumarate, zidovudine), pitavastatin, raltegravir, ranitidine, or rilpivirine. (Darunavir label, Drug interactions)

No clinically significant changes in concentration were observed for doravirine when co-administered with the following agents: dolutegravir, TDF, lamivudine, elbasvir and grazoprevir, ledipasvir and sofosbuvir, ritonavir, ketoconazole, aluminum hydroxide/magnesium hydroxide/simethicone containing antacid, pantoprazole, and methadone [see Clinical Pharmacology… (Doravirine label, Drug interactions)

No clinically significant effect on the pharmacokinetics of zidovudine, its metabolite zidovudine glucuronide, or emtricitabine was observed following a single oral dose of 500 mg famciclovir coadministered with zidovudine or emtricitabine. (Famciclovir label, Drug interactions)

Zidovudine and Rifabutin No dosage adjustment for zidovudine and rifabutin is needed when megestrol acetate is coadministered with these drugs [See Clinical Pharmacology ( 12.3 )] . (Megestrol label, Drug interactions)

Drugs without Clinically Significant Interactions with ISENTRESS In drug interaction studies, raltegravir did not have a clinically meaningful effect on the pharmacokinetics of the following: hormonal contraceptives, methadone, lamivudine, tenofovir, etravirine, darunavir/ritonavir, or boceprevir. (Raltegravir label, Drug interactions)

No clinically relevant drug-drug interaction is expected when EDURANT or EDURANT PED is coadministered with maraviroc, ribavirin or the NRTIs abacavir, emtricitabine, lamivudine, stavudine and zidovudine. (Rilpivirine label, Drug interactions)