Summary

Commonly reported side effects of abacavir/lamivudine/zidovudine include: diarrhea, nausea, and nausea and vomiting. Continue reading for a comprehensive list of adverse effects.

Applies to abacavir / lamivudine / zidovudine: oral tablet.

Serious side effects

Along with its needed effects, abacavir/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 abacavir/lamivudine/zidovudine:

More common

• Chills

Less common

• Abdominal or stomach pain
• cough
• diarrhea
• fever
• headache
• muscle weakness
• nausea
• numbness or tingling of the face, feet, or hands
• pain in the joints
• pain in the muscles
• pale skin
• skin rash
• sore throat
• swelling of the feet or lower legs
• unusual feeling of discomfort or illness
• unusual tiredness or weakness
• vomiting
• yellow eyes or skin

Rare

• Black, tarry stools
• blood in the urine or stools
• pinpoint red spots on the skin
• unusual bleeding or bruising

Other side effects

Some side effects of abacavir / 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

• Bone pain
• loss of appetite
• trouble sleeping

For Healthcare Professionals

Applies to abacavir / lamivudine / zidovudine: oral tablet.

General

Many of the side effects listed occurred commonly in patients with abacavir hypersensitivity (e.g., nausea, vomiting, diarrhea, fever, lethargy, rash).^[Ref]

Hypersensitivity

Serious and sometimes fatal hypersensitivity reactions have been reported with abacavir. Such reactions have included multi-organ failure and anaphylaxis and usually occurred within the first 6 weeks of abacavir therapy (median onset: 9 to 11 days); however, abacavir hypersensitivity reactions have occurred any time during therapy.

Patients with the human leukocyte antigen subtype B*5701 (HLA-B*5701) allele are at higher risk of abacavir hypersensitivity reactions; however, such reactions have occurred in patients without the HLA-B*5701 allele. Abacavir hypersensitivity was reported in about 8% of patients in 9 clinical trials with abacavir-containing products where patients were not screened for the HLA-B*5701 allele; incidence of suspected abacavir hypersensitivity reactions was 1% in clinical trials where HLA-B*5701 carriers were excluded.

Abacavir hypersensitivity reactions have been characterized by at least 2 of the following key signs/symptoms: (1) fever; (2) rash; (3) gastrointestinal symptoms (including nausea, vomiting, diarrhea, abdominal pain); (4) constitutional symptoms (including generalized malaise, fatigue, achiness); (5) respiratory symptoms (including dyspnea, cough, pharyngitis). Almost all reactions have included fever and/or rash (usually maculopapular or urticarial); however, reactions also reported without fever or rash. Signs/symptoms reported in at least 10% of patients with hypersensitivity reaction have included rash, nausea, vomiting, diarrhea, abdominal pain, dyspnea, cough, fever, fatigue/lethargy, malaise, headache, elevated liver function tests, and myalgia. Other signs/symptoms of hypersensitivity have included mouth ulceration, sore throat, adult respiratory distress syndrome, respiratory failure, edema, lymphadenopathy, hypotension, conjunctivitis, anaphylaxis, paresthesia, lymphopenia, hepatitis, liver failure, myolysis, arthralgia, elevated creatine phosphokinase, elevated creatinine, renal failure, abnormal chest x-ray findings (mainly infiltrates, which were localized), and death.

Symptoms of abacavir hypersensitivity reaction worsened with continued therapy and generally resolved when abacavir was discontinued. Restarting abacavir after a hypersensitivity reaction has resulted in more severe symptoms within hours and included life-threatening hypotension and death. Rarely, life-threatening reactions have occurred within hours after restarting abacavir in patients who stopped it for reasons other than symptoms of hypersensitivity (or who stopped it with only 1 key symptom of hypersensitivity).^[Ref]

Common (1% to 10%): Hypersensitivity reaction

Abacavir, lamivudine, and/or zidovudine:

-Postmarketing reports: Sensitization reactions (including anaphylaxis)

Abacavir:

-Common (1% to 10%): Hypersensitivity reactions (including fever, rash [maculopapular, urticarial], fatigue, nausea, vomiting, diarrhea, abdominal pain, pharyngitis, malaise, achiness, dyspnea, cough, lethargy, headache, myalgia, arthralgia, myolysis, edema, abnormal chest X-ray findings [mainly localized infiltrates], paresthesia, anaphylaxis, hepatitis, liver failure, renal failure, hypotension, sore throat, adult respiratory distress syndrome, respiratory failure, death, lymphadenopathy, mucous membrane lesions [conjunctivitis, mouth ulceration], erythema multiforme, elevated liver function tests, elevated creatine phosphokinase, elevated creatinine, lymphopenia)^[Ref]

Gastrointestinal

Very common (10% or more): Nausea (up to 52%), nausea and vomiting (up to 22%), diarrhea (up to 15%)

Common (1% to 10%): Abdominal distension, abdominal discomfort and pain, gaseous symptoms, dyspeptic symptoms, constipation

Uncommon (0.1% to 1%): Dry mouth/hyposalivation

Frequency not reported: Abdominal cramps

Abacavir, lamivudine, and/or zidovudine:

-Postmarketing reports: Abdominal pain, oral mucosal pigmentation, stomatitis, dyspepsia

Abacavir:

-Common (1% to 10%): Nausea, vomiting, diarrhea

-Rare (0.01% to 0.1%): Pancreatitis

Lamivudine:

-Common (1% to 10%): Nausea, vomiting, diarrhea, abdominal pain, upper abdominal pain

-Rare (0.01% to 0.1%): Elevated serum amylase, pancreatitis

-Frequency not reported: Oral ulcerations and lesions

Zidovudine:

-Very common (10% or more): Nausea

-Common (1% to 10%): Vomiting, abdominal pain, diarrhea

-Uncommon (0.1% to 1%): Flatulence

-Rare (0.01% to 0.1%): Oral mucosa pigmentation, dyspepsia, pancreatitis^[Ref]

Pancreatitis was observed in the expanded access program for abacavir.^[Ref]

Other

Very common (10% or more): Malaise and fatigue (up to 29%)

Common (1% to 10%): Temperature regulation disturbance (fever and/or chills), pain, ear/nose/throat infections

Abacavir, lamivudine, and/or zidovudine:

-Postmarketing reports: Weakness

Abacavir:

-Common (1% to 10%): Fever, lethargy, fatigue

Lamivudine:

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

-Frequency not reported: Drug-resistant hepatitis B virus (HBV)

Zidovudine:

-Common (1% to 10%): Malaise

-Uncommon (0.1% to 1%): Fever, generalized pain, asthenia

-Rare (0.01% to 0.1%): Chills, chest pain, influenza-like syndrome

The emergence of lamivudine-resistant HBV has been reported in HIV-1/HBV-coinfected patients using lamivudine-containing antiretroviral regimens.

Dermatologic

Suspected Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients using abacavir primarily in combination with agents known to be associated with SJS and TEN, respectively.

Cases of erythema multiforme, SJS, or TEN have been reported very rarely when abacavir hypersensitivity could not be ruled out.

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 was discontinued. Discoloration has occurred as longitudinal streaks or transverse bands.^[Ref]

Very common (10% or more): Disorders of sweat and sebum (primarily dry skin; up to 19%)

Common (1% to 10%): Skin rashes, pruritus

Abacavir, lamivudine, and/or zidovudine:

-Postmarketing reports: Alopecia, erythema multiforme, Stevens-Johnson syndrome, urticaria

Abacavir:

-Common (1% to 10%): Rash (without systemic symptoms)

-Very rare (less than 0.01%): Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme

-Frequency not reported: Sweet's syndrome

Lamivudine:

-Common (1% to 10%): Rash, alopecia

Zidovudine:

-Uncommon (0.1% to 1%): Rash, pruritus

-Rare (0.01% to 0.1%): Nail and skin pigmentation, urticaria, sweating

-Frequency not reported: Nail discoloration, nailbed hyperpigmentation, leukocytoclastic vasculitis (with eosinophilia and fever)^[Ref]

Nervous system

Very common (10% or more): Headache (up to 18%)

Common (1% to 10%): Dizziness, taste impairment

Abacavir, lamivudine, and/or zidovudine:

-Postmarketing reports: Paresthesia, peripheral neuropathy, seizures, dizziness

Abacavir:

-Common (1% to 10%): Headache

Lamivudine:

-Common (1% to 10%): Headache

-Very rare (less than 0.01%): Peripheral neuropathy, paresthesia

Zidovudine:

-Very common (10% or more): Headache

-Common (1% to 10%): Dizziness

-Rare (0.01% to 0.1%): Paresthesia, somnolence, convulsions, taste disturbance, syncope

-Frequency not reported: Generalized seizures, status epilepticus, vertigo, Wernicke's syndrome^[Ref]

Hepatic

Elevated ALT (greater than 5 times the upper limit of normal [5 x ULN]) has been reported in 6% of patients.

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

Elevated GGT was observed in the expanded access program for abacavir.

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.

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

Common (1% to 10%): Elevated ALT, abnormal liver function tests

Abacavir, lamivudine, and/or zidovudine:

-Postmarketing reports: Hepatic steatosis, elevated bilirubin, elevated transaminases, posttreatment exacerbations of hepatitis B

Abacavir:

-Frequency not reported: Elevated GGT

Lamivudine:

-Uncommon (0.1% to 1%): Elevated liver enzymes (AST, ALT)

-Rare (0.01% to 0.1%): Hepatitis

-Frequency not reported: Hepatic decompensation

Zidovudine:

-Common (1% to 10%): Elevated liver enzyme levels in blood, elevated bilirubin levels in blood

-Rare (0.01% to 0.1%): Liver disorders (e.g., severe hepatomegaly with steatosis)

-Frequency not reported: Acute hepatic failure^[Ref]

Hematologic

Common (1% to 10%): Neutropenia, decreased WBCs

Abacavir, lamivudine, and/or zidovudine:

-Postmarketing reports: Aplastic anemia, anemia (including pure red cell aplasia and severe anemias progressing on therapy), lymphadenopathy, thrombocytopenia, splenomegaly

Abacavir:

-Frequency not reported: Agranulocytosis

Lamivudine:

-Uncommon (0.1% to 1%): Neutropenia, anemia, thrombocytopenia

-Very rare (less than 0.01%): Pure red cell aplasia

Zidovudine:

-Common (1% to 10%): Anemia, neutropenia, leukopenia

-Uncommon (0.1% to 1%): Thrombocytopenia, 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: Hematologic toxicity (including neutropenia, severe anemia), exacerbation of anemia^[Ref]

Neutropenia (less than 750/mm3) has been reported in 5% of patients.

Agranulocytosis has been reported after the addition of abacavir to a multi-drug regimen.

Occasionally, neutropenia and anemia reported with lamivudine were severe.

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.^[Ref]

Metabolic

Common (1% to 10%): Feeding problems (primarily anorexia/loss of appetite), hypertriglyceridemia, hyperamylasemia

Frequency not reported: Hyperglycemia

Abacavir, lamivudine, and/or zidovudine:

-Postmarketing reports: Hyperlactatemia (common), lactic acidosis (rare), anorexia/decreased appetite, redistribution/accumulation of body fat

Abacavir:

-Common (1% to 10%): Anorexia

-Frequency not reported: Lactic acidosis, hyperlactatemia, redistribution/accumulation of body fat

Lamivudine:

-Frequency not reported: Lactic acidosis, hyperlactatemia, redistribution/accumulation of body fat

Zidovudine:

-Common (1% to 10%): Anorexia

-Rare (0.01% to 0.1%): Lactic acidosis (without hypoxemia)

-Frequency not reported: Lactic acidosis, hyperlactatemia, redistribution/accumulation of body fat

Combination antiretroviral therapy:

-Frequency not reported: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance"), metabolic abnormalities (e.g., hypertriglyceridemia, hypercholesterolemia, insulin resistance, hyperglycemia, hyperlactatemia)^[Ref]

Hypertriglyceridemia (greater than 750 mg/dL), hyperamylasemia (greater than 2 x ULN), and hyperglycemia (greater than 13.9 mmol/L) have been reported in 2%, 2%, and less than 1% of patients, respectively.

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

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

Musculoskeletal

Elevated CPK (greater than 4 x ULN) has been reported in 7% of patients.

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

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]

Common (1% to 10%): Elevated creatine phosphokinase (CPK), musculoskeletal pain, muscle pain

Abacavir, lamivudine, and/or zidovudine:

-Postmarketing reports: Myalgia, arthralgia, muscle weakness, rhabdomyolysis

Lamivudine:

-Common (1% to 10%): Arthralgia, muscle disorders

-Rare (0.01% to 0.1%): Rhabdomyolysis

Zidovudine:

-Common (1% to 10%): Myalgia

-Uncommon (0.1% to 1%): Myopathy

-Frequency not reported: Symptomatic myopathy, myositis

Combination antiretroviral therapy:

-Frequency not reported: Osteonecrosis^[Ref]

Psychiatric

Common (1% to 10%): Sleep disorders, depressive disorders, anxiety

Frequency not reported: Worsening of preexisting depression

Abacavir, lamivudine, and/or zidovudine:

-Postmarketing reports: Insomnia, other sleep disorders

Lamivudine:

-Common (1% to 10%): Insomnia

Zidovudine:

-Common (1% to 10%): Insomnia

-Rare (0.01% to 0.1%): Anxiety, depression, loss of mental acuity

-Frequency not reported: Confusion, mania, grandiosity^[Ref]

Respiratory

Common (1% to 10%): Viral respiratory infections

Abacavir, lamivudine, and/or zidovudine:

-Postmarketing reports: Abnormal breath sounds/wheezing

Lamivudine:

-Common (1% to 10%): Nasal symptoms, cough

Zidovudine:

-Uncommon (0.1% to 1%): Dyspnea

-Rare (0.01% to 0.1%): Cough

Immunologic

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

Renal

Frequency not reported: Renal signs/symptoms

Genitourinary

Frequency not reported: Dysuria

Zidovudine:

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

Cardiovascular

Abacavir, lamivudine, and/or zidovudine:

-Postmarketing reports: Cardiomyopathy, vasculitis

Abacavir:

-Postmarketing reports: Myocardial infarction (MI)

Zidovudine:

-Rare (0.01% to 0.1%): Cardiomyopathy, reversible congestive heart failure, vasodilation^[Ref]

An observational study investigating the rate of MI in patients on combination antiretroviral therapy showed an increased risk of MI with the use of abacavir within the previous 6 months. A sponsor-conducted pooled analysis of clinical trials showed no excess risk of MI in abacavir-treated patients as compared with control subjects. Overall, available data from the observational cohort and from clinical trials were inconclusive.^[Ref]

Endocrine

Abacavir, lamivudine, and/or zidovudine:

-Postmarketing reports: Gynecomastia

Zidovudine:

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

Ocular

Zidovudine:

-Frequency not reported: Macular edema

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