Lamivudine / Zidovudine Side Effects

Medically reviewed by Drugs.com. Last updated on May 5, 2025.

Applies to lamivudine / zidovudine: oral tablet.

Precautions

It is very important that your doctor check the progress of you or your child at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Do not take any other medicine containing emtricitabine, lamivudine, or zidovudine (eg, Atripla®, Complera®, Emtriva®, Epivir®, Epzicom®, Retrovir®, Trizivir®, or Truvada®).

Do not take any other medicines without checking with your doctor first. To do so may increase the chance of side effects from lamivudine and zidovudine combination.

If you or your child have both HIV and hepatitis B virus (HBV) infections, liver disease can become worse when lamivudine and zidovudine treatment is stopped. Discuss any changes in your treatment and medicines with your doctor.

Zidovudine may cause some serious side effects, including blood or bone marrow problems. Symptoms of a blood or bone marrow problem include fever, chills, sore throat, pale skin, or unusual tiredness or weakness. These problems may require blood transfusion or temporarily stopping treatment with lamivudine and zidovudine combination. Check with your doctor if any new health problems or symptoms occur while you or your child are taking lamivudine and zidovudine combination.

Two rare but serious reactions to this medicine are lactic acidosis (too much acid in the blood) and liver toxicity. These are more common if you are female, very overweight (obese), or have been taking anti-HIV medicines for a long time. Call your doctor right away if you or your child have more than one of these symptoms: abdominal discomfort or cramping, dark urine, decreased appetite, diarrhea, general feeling of discomfort, light-colored stools, muscle cramping or pain, nausea, unusual tiredness or weakness, trouble breathing, vomiting, or yellow eyes or skin.

Tell your doctor if you or your child have severe muscle pain, tenderness, or weakness, especially if you take this medicine for a long time.

When you or your child start taking HIV medicines, your immune system may get stronger. If you have infections that are hidden in your body (eg, pneumonia or tuberculosis), you may notice new symptoms when your body tries to fight them. If this occurs, tell your doctor right away.

This medicine may cause a decrease or loss of body fat, especially in your face, arms, legs, or buttocks, when it is used for a long time. Talk to your doctor if you have concerns.

This medicine does not decrease the risk of transmitting the HIV infection to others through sexual contact or by contaminated blood. Make sure you understand and practice safe sex, even if your partner also has HIV. Avoid sharing needles with anyone.

Serious side effects

Along with its needed effects, lamivudine / zidovudine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking lamivudine / zidovudine:

Other side effects

Some side effects of lamivudine / zidovudine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects.

Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

For healthcare professionals

Applies to lamivudine / zidovudine: oral tablet.

General adverse events

Side effects have been reported with lamivudine and zidovudine, administered separately or together. For many of these side effects, it was not clear if they were due to lamivudine, zidovudine, the other drugs used to treat HIV infection, or the underlying disease process.^[Ref]

Nervous system

• Very common (10% or more): Headache (up to 35.1%), neuropathy (up to 12.4%), dizziness (up to 10.4%)
• Frequency not reported: Syncope, taste perversion
• Postmarketing reports: Paresthesia, peripheral neuropathy, seizures

Lamivudine:

• Common (1% to 10%): Headache
• Rare (0.01% to 0.1%): Peripheral neuropathy/neuropathy, paresthesia

Zidovudine:

• Very common (10% or more): Headache, dizziness
• Common (1% to 10%): Neuropathy, paresthesia, somnolence, taste perversion
• Rare (0.01% to 0.1%): Convulsions
• Frequency not reported: Generalized seizures, status epilepticus, vertigo, Wernicke's syndrome, hearing loss, hyperalgesia, tremor, syncope^[Ref]

In an advanced HIV disease study, headache (42%), somnolence (8%), dizziness (6%), paresthesia (6%), and taste perversion (5%) were reported with zidovudine; only headache was reported at a significantly greater rate than placebo. In this study, seizures, vertigo, hearing loss, hyperalgesia, tremor, and syncope were reported in less than 5% of patients using zidovudine.

In an asymptomatic HIV infection study, headache and dizziness were reported in 58% and 20.8% (using 1500 mg) and 62.5% and 17.9% (using 500 mg) of patients using zidovudine, respectively.^[Ref]

Gastrointestinal

• Very common (10% or more): Nausea (33%), diarrhea (18%), nausea and vomiting (13%), abdominal discomfort and pain (up to 11.3%)
• Common (1% to 10%): Abdominal cramps, dyspepsia, elevated amylase, fungal gastrointestinal (GI) infection, GI discomfort and pain, gaseous symptoms, vomiting
• Uncommon (0.1% to 1%): Pancreatitis
• Frequency not reported: Flatulence
• Postmarketing reports: Oral mucosal pigmentation, stomatitis, pancreatitis

Lamivudine:

• Common (1% to 10%): Nausea, vomiting, abdominal discomfort and pain or cramps, diarrhea
• Uncommon (0.1% to 1%): Pancreatitis, abnormal pancreatic enzymes
• Rare (0.01% to 0.1%): Elevated serum amylase

Zidovudine:

• Very common (10% or more): Nausea, GI pain, diarrhea, vomiting
• Common (1% to 10%): Abdominal discomfort and pain, fungal GI infection, GI discomfort and pain, gaseous symptoms, elevated amylase, dyspepsia
• Uncommon (0.1% to 1%): Flatulence
• Rare (0.01% to 0.1%): Oral mucosa pigmentation, pancreatitis
• Frequency not reported: Constipation, dysphagia, tongue edema, eructation, bleeding gums, rectal hemorrhage, lip edema, mouth ulcer^[Ref]

Elevated amylase (greater than 2 times the upper limit of normal [2 x ULN]) has been reported in 4.2% of patients using lamivudine plus zidovudine and 1.5% of patients using zidovudine. Incidence was higher in patients with mild laboratory abnormalities at baseline.

In an advanced HIV disease study, nausea (46%), GI pain (20%), diarrhea (12%), vomiting (6%), and dyspepsia (5%) were reported with zidovudine; only nausea was reported at a significantly greater rate than placebo. In this study, constipation, dysphagia, tongue edema, eructation, flatulence, bleeding gums, rectal hemorrhage, lip edema, and mouth ulcer were reported in less than 5% of patients using zidovudine.

In the early symptomatic HIV disease study, nausea (61%), vomiting (25%), and dyspepsia (6%) were reported with zidovudine. In an asymptomatic HIV infection study, nausea, vomiting, and constipation were reported in 57.3%, 16.4%, and 8.1% (using 1500 mg) and 51.4%, 17.2%, and 6.4% (using 500 mg) of patients using zidovudine, respectively.^[Ref]

Other

• Very common (10% or more): Malaise and fatigue (27%); ear, nose, and throat infection (up to 11.3%)
• Common (1% to 10%): Fever or chills; viral ear, nose, and throat infection; viral infection
• Postmarketing reports: Weakness

Lamivudine:

• Common (1% to 10%): Fatigue, malaise, fever

Zidovudine:

• Very common (10% or more): Asthenia, fever, malaise
• Common (1% to 10%): Ear, nose, and throat infection; viral ear, nose, and throat infection; viral infection
• Uncommon (0.1% to 1%): Generalized pain
• Rare (0.01% to 0.1%): Chills, chest pain, influenza-like syndrome
• Frequency not reported: Influenza syndrome

Antiretroviral therapy:

• Frequency not reported: Increased weight^[Ref]

In an advanced HIV disease study, asthenia (19%), fever (16%), and malaise (8%) were reported with zidovudine. In this study, chills, influenza syndrome, and chest pain were reported in less than 5% of patients using zidovudine.

In the early symptomatic HIV disease study, asthenia was reported in 69% of patients using zidovudine. In an asymptomatic HIV infection study, asthenia and malaise were reported in 10.1% and 55.6% (using 1500 mg) and 8.6% and 53.2% (using 500 mg) of patients using zidovudine, respectively.^[Ref]

Respiratory

• Very common (10% or more): Nasal signs and symptoms (20%), cough (18%), throat and tonsil discomfort and pain (up to 11.6%)
• Common (1% to 10%): Bronchitis, sinusitis, breathing disorders, upper respiratory inflammation
• Frequency not reported: Dyspnea, rhinitis
• Postmarketing reports: Abnormal breath sounds/wheezing

Lamivudine:

• Common (1% to 10%): Cough, nasal symptoms

Zidovudine:

• Common (1% to 10%): Throat and tonsil discomfort and pain, sinusitis, bronchitis, breathing disorders, upper respiratory inflammation, dyspnea
• Rare (0.01% to 0.1%): Cough
• Frequency not reported: Epistaxis, pharyngitis, rhinitis, hoarseness^[Ref]

In an advanced HIV disease study, dyspnea (5%) was reported with zidovudine. In this study, cough, epistaxis, pharyngitis, rhinitis, sinusitis, and hoarseness were reported in less than 5% of patients using zidovudine.^[Ref]

Musculoskeletal

• Very common (10% or more): Musculoskeletal pain (up to 13.5%)
• Common (1% to 10%): Myalgia, arthralgia
• Postmarketing reports: Muscle weakness, elevated creatine phosphokinase (CPK), rhabdomyolysis

Lamivudine:

• Common (1% to 10%): Arthralgia, muscle disorders
• Rare (0.01% to 0.1%): Rhabdomyolysis

Zidovudine:

• Common (1% to 10%): Musculoskeletal pain, myalgia
• Uncommon (0.1% to 1%): Myopathy
• Frequency not reported: Symptomatic myopathy, myositis, back pain, arthralgia, muscle spasm, twitch

Combination antiretroviral therapy:

• Frequency not reported: Osteonecrosis^[Ref]

Myopathy and myositis (with pathological changes similar to that produced by HIV-1 disease) have been associated with prolonged zidovudine use.

In an advanced HIV disease study, myalgia (8%) was reported with zidovudine at a significantly greater rate than placebo. In this study, back pain, arthralgia, muscle spasm, twitch, and myopathy were reported in less than 5% of patients using zidovudine.

In 1 zidovudine study, myalgias and elevated CPK occurred in 8% of treated patients with a CD4 cell count less than 200/mm3, and in none of the patients with higher CD4 cell counts. Dose reduction has not affected the course of myopathy, although drug discontinuation sometimes resulted in improvement of symptoms, generally within a month. Muscle biopsy has shown atrophic and sometimes necrotic fibers, ragged-red fibers, and large accumulations of mitochondrial and fibrillar sarcoplasmic inclusions.^[Ref]

Psychiatric

• Very common (10% or more): Insomnia and other sleep disorders (up to 11.6%)
• Common (1% to 10%): Depressive disorders

Lamivudine:

• Common (1% to 10%): Insomnia

Zidovudine:

• Common (1% to 10%): Sleep disorders, insomnia
• Rare (0.01% to 0.1%): Anxiety, depression, loss of mental acuity
• Frequency not reported: Mania, confusion, grandiosity, emotional lability, nervousness^[Ref]

In an advanced HIV disease study, insomnia (5%) was reported with zidovudine at a significantly greater rate than placebo. In this study, anxiety, confusion, depression, emotional lability, nervousness, and loss of mental acuity were reported in less than 5% of patients using zidovudine.^[Ref]

Hepatic

• Common (1% to 10%): Elevated ALT, elevated AST, abnormal liver function tests
• Uncommon (0.1% to 1%): Elevated bilirubin
• Frequency not reported: Severe hepatomegaly with steatosis, hepatic decompensation
• Postmarketing reports: Hepatic steatosis, posttreatment exacerbation of hepatitis B

Lamivudine:

• Uncommon (0.1% to 1%): Elevated liver enzymes (AST, ALT)
• Rare (0.01% to 0.1%): Hepatitis, abnormal liver function tests

Zidovudine:

• Common (1% to 10%): Elevated liver enzyme levels in blood (including ALT, AST), elevated bilirubin levels in blood
• Rare (0.01% to 0.1%): Liver disorders (e.g., severe hepatomegaly with steatosis)
• Frequency not reported: Changes in liver function tests (including increased AST levels), acute hepatic failure^[Ref]

Elevated ALT (greater than 5 x ULN), AST (greater than 5 x ULN), and bilirubin (greater than 2.5 x ULN) have been reported in 3.7%, 1.7%, and 0.8% of patients using lamivudine plus zidovudine, respectively, and 3.6%, 1.8%, and 0.4% of patients using zidovudine, respectively. Incidence was higher in patients with mild laboratory abnormalities at baseline.

Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have been reported with the use of nucleoside analogs.

Hepatic decompensation (some fatal) has been reported in patients coinfected with HIV-1 and hepatitis C virus (HCV) receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin.

Severe acute exacerbations of hepatitis have been reported in patients with hepatitis B after discontinuation of lamivudine.

In an advanced HIV disease study, changes in liver function tests (including increased AST levels) was reported in less than 5% of patients using zidovudine.

One patient with preexisting hepatitis B developed acute hepatic failure 2 weeks after starting zidovudine therapy.^[Ref]

Hematologic

• Common (1% to 10%): Neutropenia, anemia, lymphatic signs/symptoms, decreased white cells
• Uncommon (0.1% to 1%): Thrombocytopenia
• Postmarketing reports: Anemia (including pure red cell aplasia and anemias progressing on therapy), lymphadenopathy, splenomegaly

Lamivudine:

• Uncommon (0.1% to 1%): Neutropenia, anemia, thrombocytopenia, decreased white cells
• Very rare (less than 0.01%): Pure red cell aplasia

Zidovudine:

• Very common (10% or more): Granulocytopenia, anemia
• Common (1% to 10%): Neutropenia, leukopenia, lymphatic signs/symptoms, decreased white cells, thrombocytopenia
• Uncommon (0.1% to 1%): Pancytopenia (with marrow hypoplasia)
• Rare (0.01% to 0.1%): Pure red cell aplasia
• Very rare (less than 0.01%): Aplastic anemia
• Frequency not reported: Exacerbation of anemia, hemolytic anemia, hematologic toxicity (including neutropenia, severe anemia), lymphadenopathy^[Ref]

Neutropenia (absolute neutrophil count less than 750/mm3), anemia (hemoglobin less than 8 g/dL), and thrombocytopenia (platelets less than 50,000/mm3) have been reported in 7.2%, 2.9%, and 0.4% of patients using lamivudine plus zidovudine, respectively, and 5.4%, 1.8%, and 1.3% of patients using zidovudine, respectively. Incidence was higher in patients with mild laboratory abnormalities at baseline.

Occasionally, neutropenia and anemia reported with lamivudine were severe.

Granulocytopenia (less than 750/mm3) has been reported in 6.4% (CD4 up to 500 using 1500 mg), 1.8% (CD4 up to 500 using 500 mg), 4% (CD4 greater than 200 using 1200 mg), 10% (CD4 greater than 200 using 1500 mg), and 47% (CD4 less than 200 using 1500 mg) of patients using zidovudine. Anemia (hemoglobin less than 8 g/dL) has been reported in 6.4% (CD4 up to 500 using 1500 mg), 1.1% (CD4 up to 500 using 500 mg), 4% (CD4 greater than 200 using 1200 mg), 3% (CD4 greater than 200 using 1500 mg), and 29% (CD4 less than 200 using 1500 mg) of patients using zidovudine.

Zidovudine has been associated with hematologic toxicity (including neutropenia and severe anemia), particularly in patients with advanced HIV-1 disease. Anemia, neutropenia, and leukopenia were reported more often with higher doses (1200 to 1500 mg/day) and in patients with advanced HIV disease (especially with poor bone marrow reserve at baseline) and particularly in those with CD4 cell counts less than 100/mm3. These hematological effects were generally observed after 4 to 6 weeks of therapy. Incidence of neutropenia increased in patients with low neutrophil counts, hemoglobin levels, and serum vitamin B12 levels at baseline.

Exacerbation of anemia has been reported in HIV-1/HCV-coinfected patients using zidovudine and ribavirin.

In an advanced HIV disease study, lymphadenopathy was reported in less than 5% of patients using zidovudine.^[Ref]

Metabolic

• Common (1% to 10%): Anorexia and/or decreased appetite
• Postmarketing reports: Hyperglycemia, redistribution/accumulation of body fat, lactic acidosis

Lamivudine:

• Very rare (less than 0.01%): Lactic acidosis
• Postmarketing reports: Hyperlactatemia (common), lactic acidosis (rare), redistribution/accumulation of body fat

Zidovudine:

• Very common (10% or more): Anorexia
• Rare (0.01% to 0.1%): Lactic acidosis (without hypoxemia)
• Frequency not reported: Redistribution/accumulation of body fat, hyperlactatemia

Antiretroviral therapy:

• Frequency not reported: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance"), increased blood lipid levels, increased glucose levels^[Ref]

Lactic acidosis and severe hepatomegaly with steatosis (including fatal cases) have been reported with the use of nucleoside analogs.

In an advanced HIV disease study, anorexia (11%) was reported with zidovudine. In this study, redistribution/accumulation of body fat was reported in less than 5% of patients using zidovudine.

In an asymptomatic HIV infection study, anorexia was reported in 19.3% (using 1500 mg) and 20.1% (using 500 mg) of patients using zidovudine.

Redistribution/accumulation of body fat has been reported with antiretroviral therapy; causality has not been established.^[Ref]

Dermatologic

• Common (1% to 10%): Skin rashes, sweating, fungal skin infection, acne and folliculitis, viral skin infection
• Frequency not reported: Pruritus
• Postmarketing reports: Alopecia, erythema multiforme, Stevens-Johnson syndrome, urticaria

Lamivudine:

• Common (1% to 10%): Rash, alopecia
• Rare (0.01% to 0.1%): Angioedema

Zidovudine:

• Very common (10% or more): Rash
• Common (1% to 10%): Sweating/diaphoresis, fungal skin infection, acne and folliculitis, viral skin infection
• Uncommon (0.1% to 1%): Pruritus
• Rare (0.01% to 0.1%): Nail and skin pigmentation, urticaria
• Frequency not reported: Lipoatrophy, skin and nailbed pigmentation changes, toxic epidermal necrolysis, leukocytoclastic vasculitis (with eosinophilia and fever), nail hyperpigmentation (rarely accompanied by mucocutaneous pigmentation or hypertrichosis), body odor^[Ref]

In an advanced HIV disease study, rash (17%) and diaphoresis (5%) were reported with zidovudine. In this study, acne, pruritus, urticaria, nail pigmentation, and body odor were reported in less than 5% of patients using zidovudine.

Bluish or brownish-black discoloration of nails has developed during the first 1 or 2 months of zidovudine therapy and usually disappeared within 2 months if the drug is discontinued. Discoloration has occurred as longitudinal streaks or transverse bands.^[Ref]

Cardiovascular

• Frequency not reported: Phlebitis
• Postmarketing reports: Cardiomyopathy, vasculitis

Zidovudine:

• Rare (0.01% to 0.1%): Cardiomyopathy
• Frequency not reported: Vasodilation^[Ref]

In an advanced HIV disease study, vasodilation was reported in less than 5% of patients using zidovudine.^[Ref]

Immunologic

• Frequency not reported: Immune reconstitution/reactivation syndrome, autoimmune disorders in the setting of immune reconstitution (e.g., Graves' disease, polymyositis, Guillain-Barre syndrome)

Ocular

• Frequency not reported: Disturbances of vision

Zidovudine:

• Frequency not reported: Amblyopia, photophobia, macular edema^[Ref]

In an advanced HIV disease study, amblyopia and photophobia were reported in less than 5% of patients using zidovudine.

At least 1 case of macular edema was deemed definitively associated with zidovudine in a patient with history of anterior uveitis secondary to syphilis.^[Ref]

Hypersensitivity

• Postmarketing reports: Sensitization reactions (including anaphylaxis)

Zidovudine:

• Frequency not reported: Sensitization reactions (including anaphylaxis)^[Ref]

Endocrine

• Postmarketing reports: Gynecomastia

Zidovudine:

• Rare (0.01% to 0.1%): Gynecomastia^[Ref]

Genitourinary

Zidovudine:

• Rare (0.01% to 0.1%): Urinary frequency
• Frequency not reported: Urinary hesitancy, dysuria, polyuria^[Ref]

In an advanced HIV disease study, urinary frequency, urinary hesitancy, dysuria, and polyuria were reported in less than 5% of patients using zidovudine.^[Ref]

See also:

Further information

Lamivudine/zidovudine side effects can vary depending on the individual. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Note: Medication side effects may be underreported. If you are experiencing side effects that are not listed, submit a report to the FDA by following this guide.

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