Does Combivir (lamivudine and zidovudine) cause side effects?

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

Serious side effects of Combivir include

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.

What are the important side effects of Combivir (lamivudine and zidovudine)?

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

Accumulation or redistribution of fat also may occur.

Combivir (lamivudine and zidovudine) side effects list for healthcare professionals

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

Adverse Reaction Epivir plus Retrovir
(n = 251)
Body as a whole
  Headache 35%
  Malaise & fatigue 27%
  Fever or chills 10%
Digestive
  Nausea 33%
  Diarrhea 18%
  Nausea & vomiting 13%
  Anorexia and/or decreased appetite 10%
  Abdominal pain 9%
  Abdominal cramps 6%
  Dyspepsia 5%
Nervous system
  Neuropathy 12%
  Insomnia & other sleep disorders 11%
  Dizziness 10%
  Depressive disorders 9%
Respiratory
  Nasal signs & symptoms 20%
  Cough 18%
Skin
  Skin rashes 9%
Musculoskeletal
  Musculoskeletal pain 12%
  Myalgia 8%
  Arthralgia 5%

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 daya

Test
(Abnormal Level)
Epivir plus Retrovir
% (n)
Neutropenia (ANC <750/mm3) 7.2% (237)
Anemia (Hgb <8.0 g/dL) 2.9% (241)
Thrombocytopenia (platelets <50,000/mm3) 0.4% (240)
ALT (>5.0 x ULN) 3.7% (241)
AST (>5.0 x ULN) 1.7% (241)
Bilirubin (>2.5 x ULN) 0.8% (241)
Amylase (>2.0 x ULN) 4.2% (72)
ULN = Upper limit of normal.
ANC = Absolute neutrophil count.
n = Number of subjects assessed.
a Frequencies of these laboratory abnormalities were higher in subjects with mild laboratory abnormalities at baseline.

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
Endocrine And Metabolic
Gastrointestinal
  • Oral mucosal pigmentation, stomatitis.
General
Hemic And Lymphatic
Hepatic And Pancreatic
  • Lactic acidosis and hepatic steatosis, pancreatitis, posttreatment exacerbations of hepatitis B.
Hypersensitivity
Musculoskeletal
  • Muscle weakness, CPK elevation, rhabdomyolysis.
Nervous
Respiratory
Skin

What drugs interact with Combivir (lamivudine and zidovudine)?

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.

Treatment & Diagnosis

Medications & Supplements

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Report Problems to the Food and Drug Administration

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Medically Reviewed on 12/31/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.