Side Effects of Combivir (lamivudine and zidovudine)

Combivir (lamivudine and zidovudine) is a combination of antiviral drugs used, in combination with other agents, to treat human immunodeficiency virus (HIV) infection.

Combivir helps to decrease the amount of HIV in the body so the immune system can work better. This lowers the chance of getting HIV complications (such as new infections, cancer) and improves quality of life. Combivir is not a cure for HIV infection. 

Common side effects of Combivir include

• chills,
• rash,
• abdominal pain,
• nausea and vomiting,
• weight loss,
• headache,
• diarrhea,
• weakness,
• cough,
• insomnia, and
• accumulation or redistribution of fat.

Serious side effects of Combivir include

• decreased blood cells,
• muscle pain,
• muscle breakdown (rhabdomyolysis),
• pancreatitis,
• liver enlargement,
• immune reconstitution syndrome,
• exacerbation of hepatitis B,
• fatty liver,
• hypersensitivity reactions, and
• metabolic disturbance (lactic acidosis).

Drug interactions of Combivir include fluconazole, probenecid, trimethoprim, and valproic acid, which reduce the elimination of zidovudine and therefore increase the concentration in blood of zidovudine. This can lead to increased side effects from zidovudine.

• Lamivudine and zalcitabine reduce the action of one another. Therefore, Combivir should not be combined with zalcitabine.
• Stavudine or doxorubicin reduce the activity of zidovudine and should not be combined with Combivir. Combining zidovudine with ganciclovir, interferon alfa, ribavirin, or other drugs that suppress bone marrow production of blood cells increases the effect of zidovudine on production of blood cells. 

Use of Combivir during pregnancy has not been adequately evaluated. However, use of zidovudine by HIV infected women reduces the transmission of HIV to the baby. 

Use of Combivir by nursing mothers has not been studied. The drugs in Combivir are excreted in breast milk. HIV infected mothers should not breastfeed because of the potential risk of transmitting HIV to an infant that is not infected.

The most serious side effects of Combivir are

• a decrease in blood cells,
• muscle pain (myopathy),
• muscle breakdown (rhabdomyolysis),
• pancreatitis,
• liver enlargement,
• immune reconstitution syndrome,
• exacerbation of hepatitis B,
• fatty liver,
• hypersensitivity reactions, and
• metabolic disturbance (lactic acidosis).

Other side effects include

• chills,
• rash,
• abdominal pain,
• nausea and vomiting,
• weight loss,
• headache,
• diarrhea,
• weakness,
• cough, and
• insomnia.

Accumulation or redistribution of fat also may occur.

The following adverse reactions are discussed in other sections of the labeling:

• Hematologic toxicity, including neutropenia and anemia
• Symptomatic myopathy
• Lactic acidosis and severe hepatomegaly with steatosis
• Exacerbations of hepatitis B
• Hepatic decompensation in patients co-infected with HIV-1 and hepatitis C
• Exacerbation of anemia in HIV-1/HCV co-infected patients receiving ribavirin and zidovudine
• Pancreatitis
• Immune reconstitution syndrome
• Lipoatrophy

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Lamivudine Plus Zidovudine Administered As Separate Formulations

In 4 randomized, controlled trials of Epivir 300 mg per day plus Retrovir 600 mg per day, the following selected adverse reactions and laboratory abnormalities were observed (Tables 1 and 2).

Table 1. Selected Clinical Adverse Reactions (Greater than or Equal to 5% Frequency) in 4 Controlled Clinical Trials with Epivir 300 mg per day and Retrovir 600 mg per day

Pancreatitis was observed in 9 of the 2,613 adult subjects (0.3%) who received Epivir in controlled clinical trials.

Selected laboratory abnormalities observed during therapy are listed in Table 2.

Table 2. Frequencies of Selected Laboratory Abnormalities among Adults in 4 Controlled Clinical Trials of Epivir 300 mg per day plus Retrovir 600 mg per day^a

Postmarketing Experience

The following adverse reactions have been identified during postmarketing use. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Body As A Whole

• Redistribution/accumulation of body fat.

Cardiovascular

• Cardiomyopathy.

Endocrine And Metabolic

• Gynecomastia, hyperglycemia.

Gastrointestinal

• Oral mucosal pigmentation, stomatitis.

General

• Vasculitis, weakness.

Hemic And Lymphatic

• Anemia, (including pure red cell aplasia and anemias progressing on therapy), lymphadenopathy, splenomegaly.

Hepatic And Pancreatic

• Lactic acidosis and hepatic steatosis, pancreatitis, posttreatment exacerbations of hepatitis B.

Hypersensitivity

• Sensitization reactions (including anaphylaxis), urticaria.

Musculoskeletal

• Muscle weakness, CPK elevation, rhabdomyolysis.

Nervous

• Paresthesia, peripheral neuropathy, seizures.

Respiratory

• Abnormal breath sounds/wheezing.

Skin

• Alopecia, erythema multiforme, Stevens-Johnson syndrome.

Zidovudine

Agents Antagonistic With Zidovudine

Concomitant use of zidovudine with the following drugs should be avoided since an antagonistic relationship has been demonstrated in vitro:

• Stavudine
• Doxorubicine
• 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

Lamivudine

Sorbitol

Coadministration of single doses of lamivudine and sorbitol resulted in a sorbitol dose-dependent reduction in lamivudine exposures. When possible, avoid use of sorbitol . When possible, avoid use of sorbitol. When possible, avoid use of sorbitol-containing medicines with lamivudine-containing medicines.