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Lamivudine / zidovudine Side Effects

Medically reviewed by Drugs.com. Last updated on Nov 18, 2023.

Applies to lamivudine / zidovudine: oral tablet.

Warning

Oral route (Tablet)

Zidovudine has been associated with hematologic toxicity including neutropenia and severe anemia, particularly in patients with advanced Human Immunodeficiency Virus (HIV-1) disease.Prolonged use of zidovudine has been associated with symptomatic myopathy.Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, including lamivudine and zidovudine. Discontinue lamivudine / zidovudine if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur.Severe acute exacerbations of hepatitis B have been reported in patients who are co-infected with hepatitis B virus (HBV) and HIV-1 and have discontinued lamivudine. 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 co-infected with HIV-1 and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted.

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:

More common

Less common

Incidence not known

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:

More common

Less common

Incidence not known

For Healthcare Professionals

Applies to lamivudine / zidovudine: oral tablet.

General

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

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]

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]

Gastrointestinal

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]

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]

Other

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]

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]

Respiratory

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]

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]

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

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]

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]

Hepatic

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]

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]

Hematologic

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]

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]

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

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]

Frequency not reported: Disturbances of vision

Zidovudine:

-Frequency not reported: Amblyopia, photophobia, macular edema[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

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

Zidovudine:

-Rare (0.01% to 0.1%): Urinary frequency

-Frequency not reported: Urinary hesitancy, dysuria, polyuria[Ref]

References

1. Brinkman K, terHofstede HJM, Burger DM, Smeitinkt JAM, Koopmans PP (1998) "Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway." AIDS, 12, p. 1735-44

2. (2001) "Product Information. Combivir (lamivudine-zidovudine)." Glaxo Wellcome

3. Cerner Multum, Inc. "UK Summary of Product Characteristics."

4. Cerner Multum, Inc. "Australian Product Information."

5. (2001) "Product Information. Retrovir (zidovudine)." Glaxo Wellcome

6. (2001) "Product Information. Epivir (lamivudine)." Glaxo Wellcome

7. Gallant JE, DeJesus E, Arribas JR, et al. (2006) "Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV." N Engl J Med, 354, p. 251-60

8. Panel on Antiretroviral Guidelines for Adults and Adolescents (2015) Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. https://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf

9. Rabaud C, Burty C, Grandidier M, et al. (2005) "Tolerability of postexposure prophylaxis with the combination of zidovudine-lamivudine and lopinavir-ritonavir for HIV infection." Clin Infect Dis, 40, p. 303-5

10. Piacenti FJ (2006) "An update and review of antiretroviral therapy." Pharmacotherapy, 26, p. 1111-33

11. Pavel S, Burty C, Alcaraz I, et al. (2007) "Severe liver toxicity in postexposure prophylaxis for HIV infection with a zidovudine, lamivudine and fosamprenavir/ritonavir regimen." AIDS, 21, p. 268-269

12. SaintMarc T, Partisani M, PoizotMartin I, Bruno F, Rouviere O, Lang JM, Gastaut JA, Touraine JL (1999) "A syndrome of peripheral fat wasting (Lipodystrophy) in patients receiving long-term nucleoside analogue therapy." AIDS, 13, p. 1659-67

13. Mallal SA, John M, Moore CB, James IR, McKinnon EJ (2000) "Contribution of nucleoside analogue reverse transcriptase inhibitors to subcutaneous fat wasting in patients with HIV infection." Aids, 14, p. 1309-16

14. Gertner E, Thurn JR, Williams DN, et al. (1989) "Zidovudine-associated myopathy." Am J Med, 86, p. 814-8

15. Dalakas MC, Illa I, Pezeshkpour GH, et al. (1990) "Mitochondrial myopathy caused by long-term zidovudine therapy." N Engl J Med, 322, p. 1098-105

16. Moore RD, Creagh-Kirk T, Keruly J, et al. (1991) "Long-term safety and efficacy of zidovudine in patients with advanced human immunodefiency virus disease." Arch Intern Med, 151, p. 981-6

17. O'Dowd MA, McKegney FP (1988) "Manic syndrome associated with zidovudine." JAMA, 260, p. 3587-8

18. Wright JM, Sachdev PS, Perkins RJ, Rodriguez P (1989) "Zidovudine-related mania." Med J Aust, 150, p. 339-40

19. McLeod GX, Hammer SM (1992) "Zidovudine: five years later." Ann Intern Med, 117, p. 487-501

20. Dubin G, Braffman MN (1989) "Zidovudine-induced hepatotoxicity." Ann Intern Med, 110, p. 85-6

21. Gradon JD, Chapnick EK, Sepkowitz DV (1992) "Zidovudine-induced hepatitis." J Intern Med, 231, p. 317-8

22. Puro V, Soldani F, De Carli G, Lazarevic Z, Mattioli F, Ippolito G (2003) "Drug-induced aminotransferase alterations during antiretroviral HIV post-exposure prophylaxis." AIDS, 17, p. 1988-90

23. (2004) "New once-daily HIV combination better tolerated." Expert Rev Anti Infect Ther, 2, p. 826

24. Anders KH, Abele DC (1989) "Development of nail pigmentation during zidovudine therapy." J Am Acad Dermatol, 21, p. 192-3

25. Merenich JA, Hannon RN, Gentry RH, Harrison SM (1989) "Azidothymidine-induced hyperpigmentation mimicking primary adrenal insufficiency." Am J Med, 86, p. 469-70

26. Torres RA, Lin RY, Lee M, Barr MR (1992) "Zidovudine-induced leukocytoclastic vasculitis." Arch Intern Med, 152, p. 850-1

27. Don P, Fusco F, Fried P, et al. (1990) "Nail dyschromia associated with zidovudine." Ann Intern Med, 112, p. 145-6

28. Sahai J, Conway B, Cameron D, Garber G (1991) "Zidovudine-associated hypertrichosis and nail pigmentation in an HIV-infected patient." AIDS, 5, p. 1395-6

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Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Some side effects may not be reported. You may report them to the FDA.