Lamivudine + Zidovudine + Nevirapine interactions
Checked as Lamivudine + Zidovudine + Nevirapine in this data source.
Full monograph for Lamivudine + Zidovudine + NevirapineCheck it against another medicine
Medicines
658 documented
| Medicine | Severity | Mechanism | Effect | Sources |
|---|---|---|---|---|
| Adalimumabvia Zidovudine | Major | Synergy | The use of tumor necrosis factor (TNF) blockers with other immunosuppressive or myelosuppressive agents may increase the risk of infections. Serious infections… | 6 sources — open the full entry |
| Amiodarone Hydrochloridevia Nevirapine | Major | Metabolism | Coadministration with inducers of CYP450 3A4, such as rifamycins and St. John's wort, may decrease the serum concentrations of amiodarone and its metabolite… | 7 sources — open the full entry |
| Artemether + Lumefantrinevia Nevirapine | Major | Metabolism | Coadministration of artemether-lumefantrine with the nonnucleoside reverse transcriptase inhibitors efavirenz, etravirine, or nevirapine may result in…3 documented mechanisms | 13 sources — open the full entry |
| Baricitinibvia Zidovudine | Major | Synergy | Coadministration of baricitinib with other immuno- or myelosuppressive agents may potentiate the risk of infections as well as lymphoma and other malignancies… | 4 sources — open the full entry |
| Brigatinibvia Nevirapine | Major | Metabolism | Coadministration with moderate inducers of CYP450 3A4 may decrease the plasma concentrations of brigatinib, which is partially metabolized by the isoenzyme. | 5 sources — open the full entry |
| Capmatinib Hydrochloridevia Nevirapine | Major | Metabolism | Coadministration with strong or moderate CYP450 3A4 inducers may decrease the plasma concentrations and anti-tumor activity of capmatinib. The proposed… | 5 sources — open the full entry |
| Caspofungin Acetatevia Nevirapine | Major | Metabolism | Coadministration with inducers or mixed inducer/inhibitors of certain metabolic pathways may produce clinically meaningful reductions in the plasma… | 1 sources — open the full entry |
| Clozapinevia Zidovudine | Major | Synergy | Coadministration of clozapine with other agents that can cause neutropenia or agranulocytosis may increase the risk and/or severity of hematologic toxicity. | 9 sources — open the full entry |
| Daclatasvirvia Nevirapine | Major | Metabolism | Coadministration with moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of daclatasvir, which is primarily metabolized by… | 2 sources — open the full entry |
| Daclatasvir + Sofosbuvirvia Nevirapine | Major | Metabolism | Coadministration with moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of daclatasvir, which is primarily metabolized by… | 2 sources — open the full entry |
| Deferipronevia Zidovudine | Major | Synergy | Coadministration of deferiprone and other drugs that can cause neutropenia or agranulocytosis may increase the risk and/or severity of hematologic toxicity… | 5 sources — open the full entry |
| Deflazacortvia Nevirapine | Major | Metabolism | Coadministration with potent or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of 21-desdeflazacort, the active… | 6 sources — open the full entry |
| Erdafitinibvia Nevirapine | Major | Metabolism | Coadministration with moderate inducers of CYP450 2C9 or 3A4 may decrease the plasma concentrations and therapeutic effects of erdafitinib. The mechanism is… | 7 sources — open the full entry |
| Etanerceptvia Zidovudine | Major | Synergy | The use of tumor necrosis factor (TNF) blockers with other immunosuppressive or myelosuppressive agents may increase the risk of infections. Serious infections… | 6 sources — open the full entry |
| Fentanyl Citratevia Lamivudine, Nevirapine, Zidovudine | Major | Metabolism · Unknown | Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of opioids that are primarily metabolized by the isoenzyme such as…3 documented mechanisms | 12 sources — open the full entry |
| Finerenonevia Nevirapine | Major | Metabolism | Coadministration with potent or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of finerenone, which is primarily… | 3 sources — open the full entry |
| Ganciclovirvia Lamivudine, Zidovudine | Major | Synergy · Unknown | Limited data concerning the coadministration of ganciclovir and zidovudine do not suggest the potential for a clinically significant pharmacokinetic…2 documented mechanisms | 14 sources — open the full entry |
| Golimumabvia Zidovudine | Major | Synergy | The use of tumor necrosis factor (TNF) blockers with other immunosuppressive or myelosuppressive agents may increase the risk of infections. Serious infections… | 6 sources — open the full entry |
| Infliximabvia Zidovudine | Major | Synergy | The use of tumor necrosis factor (TNF) blockers with other immunosuppressive or myelosuppressive agents may increase the risk of infections. Serious infections… | 6 sources — open the full entry |
| Interferon Alfa-2a [Recombinant]via Zidovudine | Major | Synergy | The coadministration of interferons and zidovudine (AZT) may result in severe bone marrow toxicity, most often manifested as granulocytopenia and/or… | 16 sources — open the full entry |
| Ketoconazolevia Zidovudine, Lamivudine, Nevirapine | Major | Metabolism · Synergy · Unknown | Use of hepatotoxic drugs together with ketoconazole or levoketoconazole may potentiate the risk of liver injury.3 documented mechanisms | 5 sources — open the full entry |
| Ketoconazole + Zinc Pyrithione + Aleoveravia Zidovudine, Lamivudine, Nevirapine | Major | Metabolism · Synergy · Unknown | Use of hepatotoxic drugs together with ketoconazole or levoketoconazole may potentiate the risk of liver injury.3 documented mechanisms | 5 sources — open the full entry |
| Lefamulin Acetatevia Nevirapine | Major | Metabolism | Coadministration with potent or moderate inducers of CYP450 3A4 and/or P-glycoprotein (P-gp) may significantly decrease the plasma concentrations of lefamulin… | 3 sources — open the full entry |
| Leflunomidevia Lamivudine, Nevirapine, Zidovudine | Major | Synergy | The recent, concomitant, or subsequent use (without the recommended leflunomide washout period or procedure) of other agents known to induce hepatotoxicity may…3 documented mechanisms | 4 sources — open the full entry |
| Lopinavir + Ritonavirvia Lamivudine, Nevirapine, Zidovudine | Major | Metabolism · Unknown | Coadministration with nevirapine may decrease the plasma concentrations of lopinavir, even in the presence of low-dose ritonavir as a pharmacokinetic booster…5 documented mechanisms | 18 sources — open the full entry |
| Lorlatinibvia Nevirapine, Zidovudine | Major | Metabolism | Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of lorlatinib, which has been found to be metabolized primarily by CYP450…2 documented mechanisms | 9 sources — open the full entry |
| Lurbinectedinvia Nevirapine, Zidovudine | Major | Metabolism · Synergy | Coadministration with a strong or moderate CYP450 3A4 inducer is predicted to decrease lurbinectedin systemic exposure, which may reduce its efficacy.2 documented mechanisms | 11 sources — open the full entry |
| Mavacamtenvia Nevirapine | Major | Metabolism | Coadministration with moderate to potent inducers of CYP450 2C19 and/or CYP450 3A4 may significantly decrease the plasma concentrations and therapeutic… | 1 sources — open the full entry |
| Neratinib Maleatevia Nevirapine | Major | Metabolism | Coadministration with potent or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of neratinib, which is primarily… | 6 sources — open the full entry |
| Olaparibvia Nevirapine, Zidovudine | Major | Metabolism · Synergy | Coadministration with potent and moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of olaparib, which is primarily…2 documented mechanisms | 11 sources — open the full entry |
| Ranolazinevia Nevirapine | Major | Metabolism | Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of ranolazine, which is primarily metabolized by the isoenzyme. | 12 sources — open the full entry |
| Rifampicinvia Lamivudine, Nevirapine, Zidovudine | Major | Metabolism · Unknown | Coadministration with rifampin may substantially decrease the plasma concentrations of nevirapine, although a few studies have suggested that the combination…3 documented mechanisms | 20 sources — open the full entry |
| Rifampicin + Isoniazidvia Lamivudine, Nevirapine, Zidovudine | Major | Metabolism · Unknown | Coadministration with rifampin may substantially decrease the plasma concentrations of nevirapine, although a few studies have suggested that the combination…6 documented mechanisms | 20 sources — open the full entry |
| Rifampicin + Isoniazid + Pyrazinamide + Ethambutolvia Lamivudine, Zidovudine, Nevirapine | Major | Metabolism · Unknown | Coadministration with rifampin may substantially decrease the plasma concentrations of nevirapine, although a few studies have suggested that the combination…12 documented mechanisms | 20 sources — open the full entry |
| Rimegepantvia Nevirapine | Major | Metabolism | Coadministration with strong or moderate inducers of CYP450 3A4 may significantly reduce the plasma concentrations and therapeutic effects of rimegepant, which… | 3 sources — open the full entry |
| Selpercatinibvia Nevirapine | Major | Metabolism | Coadministration with potent or moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of selpercatinib, which is primarily… | 3 sources — open the full entry |
| Sofosbuvir + Velpatasvirvia Nevirapine | Major | Metabolism | Coadministration with potent or moderate inducers of CYP450 isoenzymes may decrease the plasma concentrations of velpatasvir, which has been shown in vitro to… | 3 sources — open the full entry |
| Tofacitinibvia Nevirapine, Zidovudine | Major | Metabolism · Others | Coadministration of tofacitinib with other immuno- or myelosuppressive agents may potentiate the risk of infections as well as lymphoma and other malignancies…2 documented mechanisms | 3 sources — open the full entry |
| Upadacitinibvia Nevirapine, Zidovudine | Major | Metabolism · Others | Coadministration of upadacitinib with other immuno- or myelosuppressive agents may potentiate the risk of infections as well as lymphoma and other malignancies.2 documented mechanisms | 8 sources — open the full entry |
| Venetoclaxvia Nevirapine, Zidovudine | Major | Metabolism · Synergy | Coadministration with potent and moderate inducers of CYP450 3A4 may significantly decrease the plasma concentrations of venetoclax, which is primarily…2 documented mechanisms | 16 sources — open the full entry |
| Abametapirvia Nevirapine | Moderate | Metabolism | Based on in vitro inhibition data, a single topical application of abametapir lotion may increase plasma concentrations of drugs that are substrates of CYP450… | 1 sources — open the full entry |
| Abemaciclibvia Nevirapine, Zidovudine | Moderate | Metabolism · Synergy | Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of abemaciclib and its pharmacologically active metabolites, all of which…2 documented mechanisms | 10 sources — open the full entry |
| Abiraterone Acetatevia Nevirapine | Moderate | Metabolism | Coadministration with nevirapine may decrease the plasma concentrations and therapeutic efficacy of drugs that are substrates of CYP450 3A4. The proposed… | 4 sources — open the full entry |
| Acalabrutinibvia Nevirapine, Zidovudine | Moderate | Metabolism · Synergy | Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of acalabrutinib, which is primarily metabolized by the isoenzyme.2 documented mechanisms | 10 sources — open the full entry |
| Acyclovir + Hydrocortisonevia Lamivudine, Nevirapine, Zidovudine | Moderate | Others · Synergy · Unknown | Prolonged use of certain nucleoside reverse transcriptase inhibitors may commonly cause myopathy, including rare cases of rhabdomyolysis. It is not known if…6 documented mechanisms | 13 sources — open the full entry |
| Afliberceptvia Zidovudine | Moderate | Synergy | Coadministration of zidovudine with other bone marrow depressive or cytotoxic agents may increase the risk and/or severity of zidovudine hematologic toxicity… | 8 sources — open the full entry |
| Albendazolevia Nevirapine | Moderate | Metabolism | Coadministration with nevirapine may decrease the plasma concentrations and therapeutic efficacy of drugs that are substrates of CYP450 3A4. The proposed… | 4 sources — open the full entry |
| Alpelisibvia Nevirapine | Moderate | Metabolism | Coadministration of alpelisib with inducers of CYP450 3A4 may reduce the plasma concentrations of alpelisib. The proposed mechanism, based on in vitro data, is… | 2 sources — open the full entry |
| Alprazolamvia Lamivudine, Zidovudine, Nevirapine | Moderate | Metabolism · Others · Unknown | Coadministration with nevirapine may decrease the plasma concentrations and therapeutic efficacy of drugs that are substrates of CYP450 3A4. The proposed…3 documented mechanisms | 16 sources — open the full entry |
| Amlodipine Besilatevia Lamivudine, Zidovudine, Nevirapine | Moderate | Metabolism · Unknown | Coadministration with nevirapine may decrease the plasma concentrations and therapeutic efficacy of drugs that are substrates of CYP450 3A4. The proposed…3 documented mechanisms | 4 sources — open the full entry |
Food & lifestyle
high-fat foods
MinorAbsorption
Food may have variable effects on the oral bioavailability of zidovudine. Fatty foods have been reported to decrease the rate and extent of zidovudine absorption following oral administration.
What to do: Food may have variable effects on the oral bioavailability of zidovudine. Fatty foods have been reported to decrease the rate and extent of zidovudine absorption following oral administration. In a study of 13 AIDS patients, mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of zidovudine were 2.8 and 1.4 times higher, respectively, in fasting patients than in those administered the medication with breakfast. In addition, variations in plasma zidovudine concentrations were increased when administered in the fed state. In another study of eight patients, the time to reach peak concentration (Tmax) was increased from 0.68 to 1.95 hours, and Cmax was reduced by 50% when zidovudine was administered with a liquid high-fat meal relative to fasting. Protein meals can also delay the absorption and reduce the Cmax of zidovudine, although the extent of absorption is not significantly affected. The clinical significance of these alterations, if any, is unknown. The product labeling states that zidovudine may be taken with or without food.
4 sources
- Lotterer E, Ruhnke M, Trautman M, et al. "Decreased and variable systemic availability of zidovudine in patients with AIDS if administered with a meal." Eur J Clin Pharmacol 40 (1991): 305-8
- Unadkat JD, Collier AC, Crosby SS, et al. "Pharmacokinetics of oral zidovudine (azidothymidine) in patients with AIDS when administered with and without a high-fat meal." AIDS 4 (1990): 229-32
- "Product Information. Retrovir (zidovudine)." Glaxo Wellcome (2001):
- Sahai J, Gallicano K, Garber G, et al. "The effect of a protein meal on zidovudine pharmacokinetics in HIV-infected patients." Br J Clin Pharmacol 33 (1992): 657-60
Conditions
Conditions in which Lamivudine + Zidovudine + Nevirapine needs care, as documented in this source.
Bone Marrow Failure Disorders
MajorZidovudine (AZT) may cause bone marrow toxicity, most commonly manifested as granulocytopenia and anemia, particularly in patients with advanced, symptomatic HIV disease. Thrombocytopenia not related to HIV may also occasionally occur. Zidovudine should be given with extreme caution to patients with preexisting bone marrow depression (indicated by a granulocyte count below 1000 cells/mm3 or hemoglobin less than 9.5 g/dL) or blood dyscrasias. Routine blood counts are recommended, and generally should occur more frequently in patients with advanced HIV disease. Dosage reductions may be necessary.
4 sources
- Goldsmith JC, Irvine W "Reversible agranulocytosis related to azidothymidine therapy." Am J Hematol 30 (1989): 263-4
- Baum MK, Javier JJ, Mantero-Atienza E, et al. "Zidovudine-associated adverse reactions in a longitudinal study of asymptomatic HIV-1-infected homosexual males." J Acquir Immune Defic Syndr 4 (1991): 1218-26
- "Product Information. Retrovir (zidovudine)." Glaxo Wellcome (2001):
- Moore RD, Fortgang I, Keruly J, Chaisson RE "Adverse events from drug therapy for human immunodeficiency virus disease." Am J Med 101 (1996): 34-40
Exanthema
MajorNevirapine can cause severe, life-threatening skin reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and hypersensitivity reactions characterized by rash, constitutional findings, and organ dysfunction including hepatic failure. Fatalities in association with these reactions have been reported. The first 6 weeks of therapy is the period of greatest risk, and intense monitoring is recommended during the first 18 weeks. In controlled clinical trials, Grade 3 and 4 rashes were reported during the first 6 weeks in 1.5 % of nevirapine-treated patients compared to 0.1% of placebo subjects. Patients who develop signs or symptoms of severe skin reactions or hypersensitivity reactions possibly related to nevirapine at any time during therapy must discontinue the drug and seek medical attention immediately. Because nevirapine-induced hepatitis and hepatic failure may be associated with hypersensitivity reactions, liver function tests should be performed in these patients as well as all patients who develop a rash within the first 18 weeks of treatment. Nevirapine should be permanently discontinued if clinical hepatitis or transaminase elevations combined with rash or other systemic symptoms occur, and should not be restarted after recovery. Nevirapine therapy should also not be restarted following severe skin or hypersensitivity reactions or a rash that is accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, eosinophilia, granulocytopenia, lymphadenopathy, or renal dysfunction. During the initial 2-week lead-in period of 200 mg/day (4 mg/kg/day in pediatric patients), the dosage of nevirapine should not be increased if any rash occurs. Dose escalation should only be attempted after the rash resolves.
2 sources
- Daquila RT, Hughes MD, Johnson VA, et al. "Nevirapine, zidovudine, and didanosine compared with zidovudine and didanosine in patients with HIV-1 infection - a randomized, double-blind, placebo-controlled trial." Ann Intern Med 124 (1996): 1019-30
- "Product Information. Viramune (nevirapine)." Boehringer-Ingelheim (2001):
Kidney Diseases
MajorPatients with clinically significant renal impairment may be at greater risk for toxicities and adverse effects from nucleoside reverse transcriptase inhibitors (NRTIs) due to decreased drug clearance. Dosage adjustments are recommended. In addition, these patients should be monitored closely during NRTI therapy, and dosages adjusted further if necessary.
4 sources
- "Product Information. HIVID (zalcitabine)." Roche Laboratories (2001):
- "Product Information. Retrovir (zidovudine)." Glaxo Wellcome (2001):
- "Product Information. Zerit (stavudine)." Bristol-Myers Squibb (2001):
- "Product Information. Epivir (lamivudine)." Glaxo Wellcome (2001):
Kidney Diseases
MajorPatients with clinically significant renal impairment may be at greater risk for toxicities and adverse effects from nucleoside reverse transcriptase inhibitors (NRTIs) due to decreased drug clearance. Dosage adjustments are recommended. In addition, these patients should be monitored closely during NRTI therapy, and dosages adjusted further if necessary.
4 sources
- "Product Information. HIVID (zalcitabine)." Roche Laboratories (2001):
- "Product Information. Retrovir (zidovudine)." Glaxo Wellcome (2001):
- "Product Information. Zerit (stavudine)." Bristol-Myers Squibb (2001):
- "Product Information. Epivir (lamivudine)." Glaxo Wellcome (2001):
Liver Diseases
MajorHepatotoxicity including lactic acidosis, severe hepatomegaly with steatosis, fulminant hepatitis, and hepatic failure has been associated with the use of some nucleoside reverse transcriptase inhibitors (NRTIs) alone or in combination with other antiretroviral agents. Therapy with NRTIs should be administered cautiously in patients with preexisting liver disease, a history of alcohol abuse, or hepatitis. Therapy should be suspended if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur. The use of abacavir is contraindicated in patients with moderate to severe hepatic impairment as its safety and efficacy has not been established on these patients.
24 sources
- Yarchoan R, Mitsuya H, Pluda JM, et al. "The National Cancer Institute phase I study of 2',3'-dideoxyinosine administration in adults with AIDS-related complex: analysis of activity and toxicity profiles." Rev Infect Dis 12 (1990): s522-33
- Dolin R, Lambert JS, Morse GD, et al. "2',3'-dideoxyinosine in patients with AIDS or AIDS-related complex." Rev Infect Dis 12 (1990): s540-51
- Lai KK, Gang DL, Zawacki JK, Cooley TP "Fulminant hepatic failure associated with 2',3'-dideoxyinosine (ddI)." Ann Intern Med 115 (1991): 283-4
- Dubin G, Braffman MN "Zidovudine-induced hepatotoxicity." Ann Intern Med 110 (1989): 85-6
- Shriner K, Goetz MB "Severe hepatoxicity in a patient receiving both acetaminophen and zidovudine." Am J Med 93 (1992): 94-6
- Gradon JD, Chapnick EK, Sepkowitz DV "Zidovudine-induced hepatitis." J Intern Med 231 (1992): 317-8
- Chen SC, Barker SM, Mitchell DH, et al. "Concurrent zidovudine-induced myopathy and hepatoxicity in patients treated for human immunodeficiency virus (HIV) infection." Pathology 24 (1992): 109-11
- "Product Information. Videx (didanosine)." Bristol-Myers Squibb (2002):
Show all 24 sourcesShow fewer sources
- "Product Information. HIVID (zalcitabine)." Roche Laboratories (2001):
- "Product Information. Retrovir (zidovudine)." Glaxo Wellcome (2001):
- Pike IM, Nicaise C "The didanosine Expanded Access Program: safety analysis." Clin Infect Dis 16 (1993): S63-8
- Shintaku M, Nasu K, Shimizu T "Fulminant hepatic failure in an AIDS patient: possible zidovudine- induced hepatotoxicity." Am J Gastroenterol 88 (1993): 464-6
- Montaner JSG, Rachlis A, Beaulieu R, Gill J, Schlech W, Phillips P, Auclair C, Boulerice F, Schindzielorz A, Smaldone L, Wainber "Safety profile of didanosine among patients with advanced HIV disease who are intolerant to or deteriorate despite zidovudine therapy: results of the canadian open ddi treatment program." J Acquir Immune Defic Syndr 7 (1994): 924-30
- "Product Information. Epivir (lamivudine)." Glaxo Wellcome (2001):
- "Product Information. Ziagen (abacavir)." Glaxo Wellcome (2001):
- Miller KD, Cameron M, Wood LV, Dalakas MC, Kovacs JA "Lactic acidosis and hepatic steatosis associated with use of stavudine: report of four cases." Ann Intern Med 133 (2000): 192-6
- Lhouri S, Cushing H "Lactic acidosis secondary to nucleoside analog antiretroviral therapy." Infect Med 17 (2000): 547-54
- Pai VB, Koranyi K, Nahata MC "Acute hepatitis and bleeding possibly induced by zidovudine and ritonavir in an infant with HIV infection." Pharmacotherapy 20 (2000): 1135-40
- Lonergan JT, Behling C, Pfander H, Hassanein TI, Mathews WC "Hyperlactatemia and hepatic abnormalities in 10 human immunodeficiency virus-infected patients receiving nucleoside analogue combination regimens." Clin Infect Dis 31 (2000): 162-6
- Kronenberg A, Riehle HM, Gunthard HF "Liver failure after long-term nucleoside antiretroviral therapy." Lancet 358 (2001): 759-601
- Boubaker K, Flepp M, Sudre P, et al. "Hyperlactatemia and Antiretroviral Therapy: The Swiss HIV Cohort Study." Clin Infect Dis 33 (2001): 1931-7
- Coghlan ME, Sommadossi JP, Jhala NC, Many WJ, Saag MS, Johnson VA "Symptomatic lactic acidosis in hospitalized antiretroviral-treated patients with human immunodeficiency virus infection: a report of 12 cases." Clin Infect Dis 33 (2001): 1914-21
- "Product Information. Viread (tenofovir)." Gilead Sciences (2001):
- "Product Information. Baraclude (entecavir)." Bristol-Myers Squibb (2005):
Liver Diseases
MajorThe use of nevirapine has been associated with severe, life-threatening, and fatal hepatotoxicity, particularly in the first 18 weeks of therapy. Fulminant and cholestatic hepatitis, hepatic necrosis, and hepatic failure have been reported. Nevirapine-induced hepatitis and hepatic failure may be associated with signs of hypersensitivity, which can include severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, eosinophilia, granulocytopenia, lymphadenopathy, or renal dysfunction. In controlled clinical trials, symptomatic hepatic events regardless of severity occurred on average in 4% (range 0% to 11%) of patients who received nevirapine and 1.2% of patients in control groups. The risk was greatest in the first 6 weeks of therapy and continued to be greater in the nevirapine groups compared to controls through 18 weeks of treatment. In general, the patients at greatest risk of hepatic events are women with high CD4 counts. During the first 6 weeks of treatment, women have a 3-fold higher risk than men for symptomatic, often rash-associated, hepatic events (5.8% vs. 2.2%). In a retrospective review, women with CD4 counts greater than 250 cells/mm3 had a 12-fold higher risk of symptomatic hepatic events compared to women with lower CD4 counts (11% vs. 0.9%). A 5-fold increased risk was observed in men with CD4 counts greater than 400 cells/mm3 compared to men with lower CD4 counts (6.3% vs. 1.2%). Additionally, coinfection with hepatitis B or C and/or increased liver function tests at the start of therapy are associated with a greater risk of later symptomatic events (6 weeks or more after starting nevirapine) and asymptomatic increases in AST or ALT. Therapy with nevirapine should be administered cautiously in patients with preexisting liver disease or liver function test abnormalities. Due to the risk of drug accumulation, nevirapine should not be administered to patients with severe hepatic impairment. All patients treated with nevirapine should undergo intensive clinical and laboratory monitoring (i.e., once a month or more) during the first 18 weeks of therapy, and regular monitoring thereafter. Liver function tests should be performed at baseline, prior to dose escalation, and at two weeks post-dose escalation. Patients should be instructed to discontinue nevirapine and seek medical attention promptly if signs and symptoms of hepatic injury or hypersensitivity develop such as fever, pruritus, rash, facial edema, anorexia, nausea, vomiting, fatigue, right upper quadrant pain, dark urine, and jaundice. Nevirapine should be permanently discontinued if clinical hepatitis or transaminase elevations combined with rash or other systemic symptoms occur, and should not be restarted after recovery. In some cases, hepatic injury progresses despite discontinuation of treatment.
2 sources
- Cheeseman SH, Hattox SE, McLaughlin MM, Koup RA, Andrews C, Bova CA, Pav JW, Roy T, Sullivan JL, Keirns JJ "Pharmacokinetics of nevirapine: initial single-rising-dose study in humans." Antimicrob Agents Chemother 37 (1993): 178-82
- "Product Information. Viramune (nevirapine)." Boehringer-Ingelheim (2001):
Liver Diseases
MajorHepatotoxicity including lactic acidosis, severe hepatomegaly with steatosis, fulminant hepatitis, and hepatic failure has been associated with the use of some nucleoside reverse transcriptase inhibitors (NRTIs) alone or in combination with other antiretroviral agents. Therapy with NRTIs should be administered cautiously in patients with preexisting liver disease, a history of alcohol abuse, or hepatitis. Therapy should be suspended if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur. The use of abacavir is contraindicated in patients with moderate to severe hepatic impairment as its safety and efficacy has not been established on these patients.
24 sources
- Yarchoan R, Mitsuya H, Pluda JM, et al. "The National Cancer Institute phase I study of 2',3'-dideoxyinosine administration in adults with AIDS-related complex: analysis of activity and toxicity profiles." Rev Infect Dis 12 (1990): s522-33
- Dolin R, Lambert JS, Morse GD, et al. "2',3'-dideoxyinosine in patients with AIDS or AIDS-related complex." Rev Infect Dis 12 (1990): s540-51
- Lai KK, Gang DL, Zawacki JK, Cooley TP "Fulminant hepatic failure associated with 2',3'-dideoxyinosine (ddI)." Ann Intern Med 115 (1991): 283-4
- Dubin G, Braffman MN "Zidovudine-induced hepatotoxicity." Ann Intern Med 110 (1989): 85-6
- Shriner K, Goetz MB "Severe hepatoxicity in a patient receiving both acetaminophen and zidovudine." Am J Med 93 (1992): 94-6
- Gradon JD, Chapnick EK, Sepkowitz DV "Zidovudine-induced hepatitis." J Intern Med 231 (1992): 317-8
- Chen SC, Barker SM, Mitchell DH, et al. "Concurrent zidovudine-induced myopathy and hepatoxicity in patients treated for human immunodeficiency virus (HIV) infection." Pathology 24 (1992): 109-11
- "Product Information. Videx (didanosine)." Bristol-Myers Squibb (2002):
Show all 24 sourcesShow fewer sources
- "Product Information. HIVID (zalcitabine)." Roche Laboratories (2001):
- "Product Information. Retrovir (zidovudine)." Glaxo Wellcome (2001):
- Pike IM, Nicaise C "The didanosine Expanded Access Program: safety analysis." Clin Infect Dis 16 (1993): S63-8
- Shintaku M, Nasu K, Shimizu T "Fulminant hepatic failure in an AIDS patient: possible zidovudine- induced hepatotoxicity." Am J Gastroenterol 88 (1993): 464-6
- Montaner JSG, Rachlis A, Beaulieu R, Gill J, Schlech W, Phillips P, Auclair C, Boulerice F, Schindzielorz A, Smaldone L, Wainber "Safety profile of didanosine among patients with advanced HIV disease who are intolerant to or deteriorate despite zidovudine therapy: results of the canadian open ddi treatment program." J Acquir Immune Defic Syndr 7 (1994): 924-30
- "Product Information. Epivir (lamivudine)." Glaxo Wellcome (2001):
- "Product Information. Ziagen (abacavir)." Glaxo Wellcome (2001):
- Miller KD, Cameron M, Wood LV, Dalakas MC, Kovacs JA "Lactic acidosis and hepatic steatosis associated with use of stavudine: report of four cases." Ann Intern Med 133 (2000): 192-6
- Lhouri S, Cushing H "Lactic acidosis secondary to nucleoside analog antiretroviral therapy." Infect Med 17 (2000): 547-54
- Pai VB, Koranyi K, Nahata MC "Acute hepatitis and bleeding possibly induced by zidovudine and ritonavir in an infant with HIV infection." Pharmacotherapy 20 (2000): 1135-40
- Lonergan JT, Behling C, Pfander H, Hassanein TI, Mathews WC "Hyperlactatemia and hepatic abnormalities in 10 human immunodeficiency virus-infected patients receiving nucleoside analogue combination regimens." Clin Infect Dis 31 (2000): 162-6
- Kronenberg A, Riehle HM, Gunthard HF "Liver failure after long-term nucleoside antiretroviral therapy." Lancet 358 (2001): 759-601
- Boubaker K, Flepp M, Sudre P, et al. "Hyperlactatemia and Antiretroviral Therapy: The Swiss HIV Cohort Study." Clin Infect Dis 33 (2001): 1931-7
- Coghlan ME, Sommadossi JP, Jhala NC, Many WJ, Saag MS, Johnson VA "Symptomatic lactic acidosis in hospitalized antiretroviral-treated patients with human immunodeficiency virus infection: a report of 12 cases." Clin Infect Dis 33 (2001): 1914-21
- "Product Information. Viread (tenofovir)." Gilead Sciences (2001):
- "Product Information. Baraclude (entecavir)." Bristol-Myers Squibb (2005):
Muscular Diseases
MajorProlonged use of certain nucleoside reverse transcriptase inhibitors (NRTIs) such as zidovudine and telbivudine may commonly cause myopathy, including rare cases of rhabdomyolysis. The myopathy may be dose-related and is characterized by persistent, unexplained muscle aches and/or weakness in conjunction with increases in creatine phosphokinase (CPK) values. Therapy with these NRTIs should be administered cautiously in patients with preexisting myopathy or a myoneural disorder, since it may delay the recognition or confound the diagnosis of a drug-induced musculoskeletal effect. Patients should be advised to report promptly any unusual muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever. NRTI therapy should be interrupted if drug-related myopathy is suspected, and discontinued if myopathy is diagnosed.
2 sources
- "Product Information. Retrovir (zidovudine)." Glaxo Wellcome (2001):
- "Product Information. Tyzeka (telbivudine)." IDEC Pharmaceuticals Corporation (2006):
Pancreatitis
MajorThe reverse transcriptase inhibitors, didanosine (ddI), zalcitabine (ddC), stavudine (d4T) and lamivudine (3TC), may cause pancreatitis. The incidence is generally low but is approximately 7% with ddI, and up to 15% in pediatric patients given 3TC. Patients with a history of or known risk factors for pancreatitis, such as alcohol abuse or hypertriglyceridemia, should be monitored closely during therapy with these agents. Therapy should be discontinued at the first signs or symptoms suggestive of pancreatitis (e.g., nausea, vomiting, abdominal pain, hyperamylasemia with dysglycemia, rising triglycerides, decreasing serum calcium), and preferably permanently discontinued if clinical pancreatitis develops.
18 sources
- Shelton MJ, O'Donnell AM, Morse GD "Didanosine." Ann Pharmacother 26 (1992): 660-70
- Yarchoan R, Mitsuya H, Pluda JM, et al. "The National Cancer Institute phase I study of 2',3'-dideoxyinosine administration in adults with AIDS-related complex: analysis of activity and toxicity profiles." Rev Infect Dis 12 (1990): s522-33
- Dolin R, Lambert JS, Morse GD, et al. "2',3'-dideoxyinosine in patients with AIDS or AIDS-related complex." Rev Infect Dis 12 (1990): s540-51
- Bouvet E, Casalino E, Prevost MH, Vachon F "Fatal case of 2',3'-dideoxyinosine-associated pancreatitis." Lancet 336 (1990): 1515
- Maxson CJ, Greenfield SM, Turner JL "Acute pancreatitis as a common complication of 2',3'-dideoxyinosine therapy in the acquired immunodeficiency syndrome." Am J Gastroenterol 87 (1992): 708-13
- Whittington R, Brogden RN "Zalcitabine: a review of its pharmacology and clinical potential in acquired immunodeficiency syndrome (AIDS)." Drugs 44 (1992): 656-83
- Matthews SJ, Cersosimo RJ, Spivack ML "Zidovudine and other reverse transcriptase inhibitors in the management of human immunodeficiency virus-related disease." Pharmacotherapy 11 (1991): 419-49
- "Product Information. Videx (didanosine)." Bristol-Myers Squibb (2002):
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- "Product Information. HIVID (zalcitabine)." Roche Laboratories (2001):
- Pike IM, Nicaise C "The didanosine Expanded Access Program: safety analysis." Clin Infect Dis 16 (1993): S63-8
- Grasela TH, Walawander CA, Beltangady M, Knupp CA, Martin RR, Dunkle LM, Barbhaiya RH, Pittman KA, Dolin R, Valentine FT, "Analysis of potential risk factors associated with the development of pancreatitis in phase i patients with AIDS or AIDS-related complex receiving didanosine." J Infect Dis 169 (1994): 1250-5
- "Product Information. Zerit (stavudine)." Bristol-Myers Squibb (2001):
- Montaner JSG, Rachlis A, Beaulieu R, Gill J, Schlech W, Phillips P, Auclair C, Boulerice F, Schindzielorz A, Smaldone L, Wainber "Safety profile of didanosine among patients with advanced HIV disease who are intolerant to or deteriorate despite zidovudine therapy: results of the canadian open ddi treatment program." J Acquir Immune Defic Syndr 7 (1994): 924-30
- Schindzielorz A, Pike I, Daniels M, Pacelli L, Smaldone L "Rates and risk factors for adverse events associated with didanosine in the expanded access program." Clin Infect Dis 19 (1994): 1076-83
- van Leeuwen R, Lange JM, Hussey EK, Donn KH, Hall ST, Harker AJ, Jonker P, Danner SA "The safety and pharmacokinetics of a reverse transcriptase inhibitor, 3TC, in patients with HIV infection: a phase I study." AIDS 6 (1992): 1471-5
- van Leeuwen R, Katlama C, Kitchen V, Boucher CA, Tubiana R, McBride M, Ingrand D, Weber J, Hill A, McDade H, et al. "Evaluation of safety and efficacy of 3TC (lamivudine) in patients with asymptomatic or mildly symptomatic human immunodeficiency virus infection: a phase I/II study." J Infect Dis 171 (1995): 1166-71
- "Product Information. Epivir (lamivudine)." Glaxo Wellcome (2001):
- Moore RD, Fortgang I, Keruly J, Chaisson RE "Adverse events from drug therapy for human immunodeficiency virus disease." Am J Med 101 (1996): 34-40
Diseases requiring hemodialysis
ModerateNevirapine is partially removed by hemodialysis. In a pharmacokinetic study of nevirapine in patients with renal impairment, six subjects requiring hemodialysis exhibited a 44% reduction in nevirapine systemic exposure (AUC) over a one-week period. There was also evidence of accumulation of nevirapine hydroxy-metabolites in plasma in these patients; however, the clinical significance is unknown. A supplemental dose following each dialysis session is indicated for patients undergoing chronic hemodialysis.
1 source
- "Product Information. Viramune (nevirapine)." Boehringer-Ingelheim (2001):
Kidney Diseases
ModerateNevirapine metabolites are primarily eliminated by the kidney. The clinical significance of possible reduced metabolite clearance in renal impairment is uncertain. Therapy with nevirapine should be administered cautiously in patients with renal impairment.
3 sources
- Havlir D, Cheeseman SH, McLaughlin M, Murphy R, Erice A, Spector SA, Greenough TC, Sullivan JL, Hall D, Myers M, et al. "High-dose nevirapine: safety, pharmacokinetics, and antiviral effect in patients with human immunodeficiency virus infection." J Infect Dis 171 (1995): 537-45
- Cheeseman SH, Hattox SE, McLaughlin MM, Koup RA, Andrews C, Bova CA, Pav JW, Roy T, Sullivan JL, Keirns JJ "Pharmacokinetics of nevirapine: initial single-rising-dose study in humans." Antimicrob Agents Chemother 37 (1993): 178-82
- "Product Information. Viramune (nevirapine)." Boehringer-Ingelheim (2001):
Therapeutic duplication
Drug classes that overlap with Lamivudine + Zidovudine + Nevirapine, so taking both doubles up the same effect. This source publishes no per-row citations for duplication.
nnrtis
The recommended maximum number of medicines in the 'NNRTIs' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'NNRTIs' category.
Example product in the source data (US market): Emtricitabine/rilpivirine/tenofovir
nnrtis
The recommended maximum number of medicines in the 'NNRTIs' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'NNRTIs' category.
Example product in the source data (US market): Symfi lo
nnrtis
The recommended maximum number of medicines in the 'NNRTIs' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'NNRTIs' category.
Example product in the source data (US market): Doravirine/lamivudine/tenofovir
nnrtis
The recommended maximum number of medicines in the 'NNRTIs' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'NNRTIs' category.
Example product in the source data (US market): Emtricitabine/rilpivirine/tenofovir alafenamide
nnrtis
The recommended maximum number of medicines in the 'NNRTIs' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'NNRTIs' category.
Example product in the source data (US market): Efavirenz/emtricitabine/tenofovir
nnrtis
The recommended maximum number of medicines in the 'NNRTIs' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'NNRTIs' category.
Example product in the source data (US market): Juluca
nnrtis
The recommended maximum number of medicines in the 'NNRTIs' category to be taken concurrently is usually one.Your list includes two medicines belonging to the 'NNRTIs' category.
Example product in the source data (US market): Cabotegravir/rilpivirine