Version May 2024
Zidovudine, a component of lamivudine/zidovudine tablets, has been associated with hematologic toxicity, including neutropenia and severe anemia, particularly in patients with advanced HIV-1 disease.
Prolonged use of zidovudine has been associated with symptomatic myopathy.
Severe, acute exacerbations of hepatitis B have been reported in patients who are coinfected with hepatitis B virus (HBV) and HIV-1 and have discontinued lamivudine, a component of lamivudine/zidovudine. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue lamivudine/zidovudine and are coinfected with HIV-1 and HBV. If appropriate, initiation of antihepatitis B therapy may be warranted.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with use of nucleoside analogues, including lamivudine and zidovudine. Discontinue lamivudine/zidovudine if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.
Note: Because this is a fixed-dose combination product, avoid use in patients requiring dosage reduction.
HIV-1 infection, treatment: Oral: One tablet (lamivudine 150 mg/zidovudine 300 mg) twice daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl <50 mL/minute: Use is not recommended (use dose-adjusted individual components).
Use is not recommended (use dose-adjusted individual components).
(For additional information see "Zidovudine and lamivudine: Pediatric drug information")
HIV-1 infection, treatment: Note: Use in combination with other antiretroviral (ARV) agents; evaluate gene mutation and ARV resistance patterns (refer to https://www.iasusa.org and https://hivdb.stanford.edu/ for more information).
Children and Adolescents weighing ≥30 kg: Lamivudine 150 mg and zidovudine 300 mg per tablet: Oral: One tablet twice daily.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Children and Adolescents weighing ≥30 kg:
CrCl ≥50 mL/minute: No dosage adjustment necessary.
CrCl <50 mL/minute: Use of fixed-dose combination is not recommended; see individual agents.
Children and Adolescents weighing ≥30 kg: Use of fixed-dose combination is not recommended; see individual agents.
See individual agents.
Hypersensitivity to lamivudine or zidovudine, or any component of the formulation.
Canadian labeling: Additional contraindications (not in US labeling): Neutrophil count <750/mm3 or hemoglobin <7.5 g/dL (4.65 mmol/L)
Concerns related to adverse effects:
• Hematologic toxicity: [US Boxed Warning]: Zidovudine is associated with hematologic toxicity, including neutropenia and severe anemia. Use with caution in patients with bone marrow compromise (granulocytes <1,000 cells/mm3 or hemoglobin <9.5 g/dL).
• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.
• Lactic acidosis/hepatomegaly: [US Boxed Warning]: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues and other antiretrovirals. Female gender and obesity may increase the risk for development. Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or hepatotoxicity (transaminase elevation may/may not accompany hepatomegaly and steatosis).
• Lipoatrophy: Zidovudine may cause loss of subcutaneous fat, especially in the face, limbs, and buttocks. Lipoatrophy incidence and severity are related to cumulative exposure and may be only partially reversible; improvement may take months to years after switching to a regimen that does not contain zidovudine. Monitor patients for signs of lipoatrophy and consider switching to a non-zidovudine-containing regimen if lipoatrophy occurs.
• Myopathy: [US Boxed Warning]: Prolonged use of zidovudine has been associated with symptomatic myopathy.
Disease-related concerns:
• Chronic hepatitis B: [US Boxed Warning]: Severe acute exacerbations of hepatitis B have been reported in patients coinfected with HBV and HIV-1 when therapy is discontinued; monitor patients with clinical and laboratory follow-up for at least several months after treatment discontinuation. Emergence of hepatitis B virus lamivudine-resistant variants has been reported in patients with concurrent HBV infection who received a lamivudine-containing regimen for HIV-1 treatment.
• Hepatic impairment: Use is not recommended in patients with hepatic impairment.
• Pancreatitis: Use with caution in patients with a history of pancreatitis or other significant risk factors for pancreatitis development. Discontinue immediately if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur.
• Renal impairment: Use is not recommended in patients with renal impairment (CrCl <50 mL/minute).
The major clinical toxicity of lamivudine in pediatric patients is pancreatitis, which occurred in 14% of patients in one open-label, dose-escalation trial; discontinue lamivudine therapy if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur. Use with extreme caution and only if there is no satisfactory alternative therapy in pediatric patients with a history of pancreatitis or other significant risk factors for the development of pancreatitis (Epivir prescribing information 2020).
Zidovudine-related adverse hematologic effects may be concentration-dependent and associated with increasing AUC (Fillekes 2014; HHS [pediatric] 2023). Adverse cardiac effects have been associated with zidovudine therapy. A prospective study of 325 pediatric patients aged 7 to 16 years with perinatally acquired HIV evaluated associations between previous or current antiretroviral agents and cardiac echocardiogram measures. When comparing patients currently receiving zidovudine (n=107) with those who were not, zidovudine therapy was associated with increased end-systolic wall stress and slightly larger heart size. Longer duration of zidovudine use was associated with higher wall stress (Williams 2018). A descriptive study evaluated 643 individuals 1 to 25 years of age with perinatally acquired HIV to determine prevalence of early cardiac dysfunction and reported that left ventricular ejection fraction was negatively associated with history of zidovudine exposure. Implications for cardiac outcomes later in life (eg, cardiomyopathy) are unknown (McCrary 2020; Williams 2018).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Tablet, Oral:
Combivir: Lamivudine 150 mg and zidovudine 300 mg [DSC] [scored]
Generic: Lamivudine 150 mg and zidovudine 300 mg
Yes
Tablets (lamiVUDine-Zidovudine Oral)
150-300 mg (per each): $4.42 - $15.53
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Combivir: Lamivudine 150 mg and zidovudine 300 mg [contains polysorbate 80]
Generic: Lamivudine 150 mg and zidovudine 300 mg
Oral: Administer without regard to food.
Oral: May be administered without regard to meals
Hazardous agent (NIOSH 2016 [group 2]).
Zidovudine is a hazardous agent. Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage. NIOSH recommends single gloving for administration of intact tablets (NIOSH 2016). Facilities may perform assessment of some (non-antineoplastic) hazardous drugs to determine if appropriate for alternative containment strategies and handling requirements; assess risk to determine appropriate containment strategy (USP-NF 2017).
HIV-1 infection, treatment: Treatment of HIV-1 infection in combination with other antiretrovirals.
Combivir may be confused with Combivent, Epivir
AZT is an error-prone abbreviation (mistaken as azaTHIOprine, aztreonam)
Refer to individual components.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Acemetacin: May enhance the adverse/toxic effect of Zidovudine. Specifically, the risk for hematologic toxicity may be increased. Risk C: Monitor therapy
Amodiaquine: Zidovudine may enhance the neutropenic effect of Amodiaquine. Management: Avoid coadministration of zidovudine-containing antiretroviral therapy with amodiaquine when possible. If combined, monitor closely for neutropenia. Risk D: Consider therapy modification
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
Betibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Betibeglogene Autotemcel. Risk X: Avoid combination
Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Risk C: Monitor therapy
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
Clarithromycin: May enhance the myelosuppressive effect of Zidovudine. Clarithromycin may decrease the serum concentration of Zidovudine. Management: Monitor response to zidovudine closely when used with clarithromycin, and consider staggering zidovudine and clarithromycin doses when possible in order to minimize the potential for interaction. Risk D: Consider therapy modification
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification
Dexketoprofen: May enhance the adverse/toxic effect of Zidovudine. Risk C: Monitor therapy
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
DOXOrubicin (Conventional): May enhance the adverse/toxic effect of Zidovudine. DOXOrubicin (Conventional) may diminish the therapeutic effect of Zidovudine. Management: Avoid concomitant use of doxorubicin and zidovudine due to the possibility of reduced zidovudine efficacy and increased myelosuppressive effects. Risk D: Consider therapy modification
DOXOrubicin (Liposomal): May enhance the adverse/toxic effect of Zidovudine. DOXOrubicin (Liposomal) may diminish the therapeutic effect of Zidovudine. Management: Avoid concomitant use of doxorubicin and zidovudine. Reduced efficacy of zidovudine is possible based on in vitro data. Also, increased myelosuppressive effects are possible with combined administration. Risk D: Consider therapy modification
Elivaldogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Elivaldogene Autotemcel. Management: Avoid use of antiretroviral medications for at least one month, or for the amount of time required for elimination of the retroviral medication, prior to stem cell mobilization and until the all apheresis cycles are finished Risk X: Avoid combination
Erdafitinib: May increase the serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Management: Consider alternatives to this combination when possible. If combined, monitor for increased effects/toxicities of OCT2 substrates and consider OCT2 substrate dose reductions when appropriate. Risk D: Consider therapy modification
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Foslevodopa: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Ganciclovir-Valganciclovir: May enhance the adverse/toxic effect of Zidovudine. Specifically, hematologic toxicity may be enhanced. Risk C: Monitor therapy
Gilteritinib: May increase the serum concentration of OCT1 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Interferons: May enhance the adverse/toxic effect of Zidovudine. Interferons may decrease the metabolism of Zidovudine. Risk C: Monitor therapy
Levomethadone: May increase the serum concentration of Zidovudine. Risk C: Monitor therapy
Lopinavir: May decrease the serum concentration of Zidovudine. Risk C: Monitor therapy
Lovotibeglogene Autotemcel: Antiretroviral Agents may diminish the therapeutic effect of Lovotibeglogene Autotemcel. Risk X: Avoid combination
Methadone: May increase the serum concentration of Zidovudine. Risk C: Monitor therapy
Nelfinavir: May decrease the serum concentration of Zidovudine. Risk C: Monitor therapy
Nirmatrelvir and Ritonavir: May decrease the serum concentration of Zidovudine. Risk C: Monitor therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Orlistat: May decrease the serum concentration of Antiretroviral Agents. Risk C: Monitor therapy
Pacritinib: May increase the serum concentration of OCT1 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Probenecid: May increase the serum concentration of Zidovudine. Risk C: Monitor therapy
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Raltegravir: May enhance the myopathic (rhabdomyolysis) effect of Zidovudine. Risk C: Monitor therapy
Ribavirin (Oral Inhalation): Zidovudine may enhance the adverse/toxic effect of Ribavirin (Oral Inhalation). Specifically, the risk/severity of anemia may be increased. Management: Due to significantly increased risk of anemia, consider even closer monitoring for anemia than routinely recommended. Alternative therapies should be considered when clinically possible, particularly for patients with other risk factors. Risk D: Consider therapy modification
Ribavirin (Systemic): Zidovudine may enhance the adverse/toxic effect of Ribavirin (Systemic). Specifically, the risk/severity of anemia may be increased. Management: Due to significantly increased risk of anemia, consider even closer monitoring for anemia than routinely recommended for ribavirin. Alternative therapies should be considered when clinically possible, particularly for patients with other risk factors. Risk D: Consider therapy modification
RifAMPin: May decrease the serum concentration of Zidovudine. Risk C: Monitor therapy
Risdiplam: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of risdiplam with MATE substrates if possible. If the combination cannot be avoided, monitor closely for adverse effects. Consider a reduced dose of the MATE substrate according to that substrate's labeling if appropriate. Risk D: Consider therapy modification
Ritonavir: May decrease the serum concentration of Zidovudine. Risk C: Monitor therapy
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Sorbitol: May decrease the serum concentration of LamiVUDine. Management: When possible, avoid chronic coadministration of sorbitol-containing solutions with lamivudine, but if this combination cannot be avoided, monitor patients more closely for possible therapeutic failure associated with decreased lamivudine exposure. Risk D: Consider therapy modification
Stavudine: Zidovudine may diminish the therapeutic effect of Stavudine. Risk X: Avoid combination
Tafenoquine: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of MATE substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the MATE substrate and consider a reduced dose of the MATE substrate according to that substrate's labeling. Risk D: Consider therapy modification
Tafenoquine: May increase the serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of OCT2 substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the OCT2 substrate and consider a reduced dose of the OCT2 substrate according to that substrate's labeling. Risk D: Consider therapy modification
Tenoxicam: May enhance the adverse/toxic effect of Zidovudine. Risk C: Monitor therapy
Tipranavir: May decrease the serum concentration of Zidovudine. Risk C: Monitor therapy
Trimethoprim: May increase the serum concentration of LamiVUDine. Risk C: Monitor therapy
Trimethoprim: Zidovudine may enhance the neutropenic effect of Trimethoprim. Trimethoprim may increase the serum concentration of Zidovudine. Risk C: Monitor therapy
Valproate Products: May increase the serum concentration of Zidovudine. Risk C: Monitor therapy
The Health and Human Services (HHS) Perinatal HIV Guidelines consider this combination an alternative regimen for patients with HIV infection who are not yet pregnant but are trying to conceive (HHS [perinatal] 2021).
Refer to individual monographs for additional information.
The Health and Human Services (HHS) Perinatal HIV Guidelines consider lamivudine in combination with zidovudine an alternative NRTI backbone for pregnant patients with HIV infection who are antiretroviral-naive, who have had antiretroviral therapy (ART) in the past but are restarting, or who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen). Patients who become pregnant while taking this combination may continue if viral suppression is effective and the regimen is well tolerated. Although use of this combination has the most experience for use in pregnancy, it has an increased potential for hematologic toxicity and requires twice-daily dosing (HHS [perinatal] 2021).
Refer to individual monographs for additional information.
Lamivudine and zidovudine are both present in breast milk.
Refer to individual monographs for additional information.
Amylase, bilirubin, signs and symptoms of pancreatitis. Monitor CBC with differential and platelet count at least every 2 weeks, liver function tests (including signs/symptoms of hepatomegaly), MCV, serum creatinine kinase, viral load, and CD4 count; observe for appearance of opportunistic infections; signs of muscle weakness or pain; blood lactate levels and signs of acidosis
The combination of zidovudine and lamivudine is believed to act synergistically to inhibit reverse transcriptase via DNA chain termination after incorporation of the nucleoside analogue as well as to delay the emergence of mutations conferring resistance
See individual agents.
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
