Note: This document contains side effect information about abacavir. Some dosage forms listed on this page may not apply to the brand name Ziagen.

Summary

Common side effects of Ziagen include: arthralgia, cough, fatigue, lethargy, myalgia, pruritus, vomiting, chills, and malaise. Other side effects include: hypersensitivity condition, pharyngitis, and tachypnea. Continue reading for a comprehensive list of adverse effects.

Applies to abacavir: oral solution, oral tablet.

Serious side effects of Ziagen

Along with its needed effects, abacavir (the active ingredient contained in Ziagen) 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:

Less common

• Abdominal or stomach pain
• cough
• diarrhea
• difficult or labored breathing
• fever
• headache
• joint or muscle pain
• nausea
• numbness or tingling of the hands, feet, or face
• redness and soreness of the eyes
• skin rash
• sore throat
• sores in the mouth
• swelling of the feet or lower legs
• unusual feeling of discomfort or illness
• unusual tiredness
• vomiting

Rare

• Abdominal or stomach swelling
• decreased appetite
• fast, shallow breathing
• sleepiness

Incidence not known

• Blistering, peeling, or loosening of the skin
• chest pain or discomfort
• chills
• dark urine
• itching
• light-colored stools
• pain or discomfort in the arms, jaw, back, or neck
• red, irritated eyes
• red skin lesions, often with a purple center
• sores, ulcers, or white spots in the mouth or on the lips
• sweating
• unusual weakness
• upper right abdominal or stomach pain
• yellow eyes and skin

Other side effects of Ziagen

Some side effects of abacavir 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

• Headache

Less common

• Trouble sleeping

Incidence not known

• Breast enlargement
• buffalo hump
• central obesity
• facial wasting
• gaining weight around your neck, upper back, breast, face, or waist
• peripheral wasting

For Healthcare Professionals

Applies to abacavir: oral solution, oral tablet.

General

In 1 study, patients receiving the once-daily regimen had a significantly higher incidence of severe drug hypersensitivity reactions and severe diarrhea than patients on the twice-daily regimen.

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

Hypersensitivity

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

Frequency not reported: Serious and sometimes fatal hypersensitivity reactions, abacavir (the active ingredient contained in Ziagen) hypersensitivity reaction presenting as acute fibrinous and organizing pneumonia^[Ref]

Serious and sometimes fatal hypersensitivity reactions have been reported with this drug. Such reactions have included multi-organ failure and anaphylaxis and usually occurred within the first 6 weeks of 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 hypersensitivity reactions to this drug; 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, malaise, diarrhea, headache, fatigue/lethargy, abdominal pain, dyspnea, cough, fever, 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 this drug was discontinued. Restarting this drug 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 this drug in patients who stopped it for reasons other than symptoms of hypersensitivity (or who stopped it with only 1 key symptom of hypersensitivity).

In 1 case report, a 57-year-old HIV-positive male presented to medical attention with a 2-day history of fever, malaise, and diarrhea related to initiation of this drug. Six days prior to the onset of symptoms, the patient's antiretroviral therapy was switched from efavirenz and lamivudine-zidovudine to zidovudine, abacavir, and lopinavir-ritonavir after a drop in his CD4 cell count. The patient developed acute dyspnea and severe hypoxemia, hemoptysis, and diffuse bilateral pulmonary infiltrates within 72 hours of admission and this drug was discontinued due to suspicion of a hypersensitivity reaction. Three days after drug discontinuation, the patient's status improved and chest films showed resolution of infiltrates.^[Ref]

Gastrointestinal

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

Very common (10% or more): Nausea (up to 47%), nausea and vomiting (up to 38%), diarrhea (up to 16%)

Common (1% to 10%): Abdominal pain/gastritis/gastrointestinal signs and symptoms, vomiting, abdominal discomfort and pain, abnormal amylase

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

Other

Very common (10% or more): Malaise and fatigue (up to 34%), temperature regulation disturbance (up to 19%)

Common (1% to 10%): Fever/pyrexia, lethargy, fatigue, fatigue/malaise, fever and/or chills

Uncommon (0.1% to 1%): Non-site-specific pain

Frequency not reported: Asthenia, reduced alcohol tolerance, disulfiram-like reaction^[Ref]

In 1 case report, a 31-year-old HIV-infected male patient switched to this drug and experienced a disulfiram-like reaction with nausea, facial flushing, and tachycardia after alcohol consumption. When the patient was rechallenged with a shot of vodka, the same reaction occurred.

In another case, a 27-year-old HIV-infected male patient switched to this drug and noticed reduced alcohol tolerance. The patient reported that he felt as if he had ingested 1.5 bottles of wine after 3 glasses, with loss of memory until the next morning and vomiting. The patient was able to tolerate small quantities of alcohol or alcohol consumed with food.^[Ref]

Nervous system

Very common (10% or more): Headache (up to 31%)

Common (1% to 10%): Headaches/migraine, dizziness, neuropathy^[Ref]

Respiratory

Very common (10% or more): Cough (up to 24%), ear/nose/throat infections (up to 19%), nasal signs/symptoms (up to 11%)

Common (1% to 10%): Viral respiratory infections (including viral ear, nose, and throat infection), bronchitis

Frequency not reported: Tachypnea, pharyngitis^[Ref]

Musculoskeletal

Elevated creatine phosphokinase (greater than 4 times the upper limit of normal [4 x ULN]) has been reported in up to 8% of patients.^[Ref]

Very common (10% or more): Elevated creatine phosphokinase (up to 12%)

Common (1% to 10%): Musculoskeletal pain

Combination antiretroviral therapy:

-Frequency not reported: Osteonecrosis^[Ref]

Dermatologic

Suspected Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported during postmarketing experience in patients using this drug 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 (the active ingredient contained in Ziagen) hypersensitivity could not be ruled out.^[Ref]

Very common (10% or more): Skin rashes (maculopapular, urticarial, or variable appearance; up to 11%)

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

Frequency not reported: Sweet's syndrome

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

Metabolic

Hypertriglyceridemia (greater than 750 mg/dL), hyperamylasemia (greater than 2 x ULN), and hyperglycemia (greater than 13.9 mmol/L) have been reported in up to 6%, up to 4%, 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.^[Ref]

Very common (10% or more): Feeding problems (up to 11%)

Common (1% to 10%): Hypertriglyceridemia, hyperamylasemia, anorexia, abnormal triglycerides, hyperlactatemia

Uncommon (0.1% to 1%): Hyperglycemia, abnormal alkaline phosphatase, abnormal glucose, abnormal sodium

Rare (0.01% to 0.1%): Lactic acidosis

Frequency not reported: Mild elevations of blood glucose, hypoglycemia, loss of appetite

Postmarketing reports: Redistribution/accumulation of body fat (including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, "cushingoid appearance")

Combination antiretroviral therapy:

-Frequency not reported: Metabolic abnormalities (e.g., hypertriglyceridemia, hypercholesterolemia, insulin resistance, hyperglycemia, hyperlactatemia)^[Ref]

Psychiatric

Very common (10% or more): Dreams/sleep disorders (10%)

Common (1% to 10%): Depression, anxiety, sleep disorders, insomnia, abnormal dreams

Frequency not reported: Mania, worsening of preexisting depression, lethargy^[Ref]

Hepatic

Common (1% to 10%): Elevated ALT, elevated AST

Uncommon (0.1% to 1%): Abnormal bilirubin

Frequency not reported: Increased GGT, severe hepatomegaly with steatosis

Postmarketing reports: Hepatic steatosis^[Ref]

Elevated ALT (greater than 5 x ULN) and AST (greater than 5 x ULN) have been reported in 6% and up to 6% of patients, respectively.

The reported frequencies were similar to those observed during clinical trials with zidovudine and lamivudine administration.

Increased GGT was observed in the expanded access program.

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

Hematologic

Common (1% to 10%): Neutropenia, thrombocytopenia, decreased white cells, abnormal absolute neutrophils

Uncommon (0.1% to 1%): Anemia, leukopenia, abnormal hemoglobin, abnormal platelets, abnormal WBC

Rare (less than 0.1%): Eosinophilia

Frequency not reported: Agranulocytosis, increased platelet reactivity^[Ref]

Neutropenia (absolute neutrophil count less than 750/mm3), thrombocytopenia (platelets less than 50,000/mm3), anemia (hemoglobin 6.9 g/dL or less), and leukopenia (WBC 1500/mm3 or less) have been reported in up to 5%, 1%, less than 1%, and less than 1% of patients, respectively.

The reported frequencies were similar to those observed during clinical trials with zidovudine and lamivudine administration.

Agranulocytosis has been reported after the addition of this drug to a multi-drug regimen.^[Ref]

Renal

Uncommon (0.1% to 1%): Renal signs/symptoms, abnormal creatinine

Frequency not reported: Acute renal failure, interstitial nephritis^[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)

Cardiovascular

Frequency not reported: Endothelial dysfunction, peripheral arterial disease, coronary bypass surgery, ischemic stroke, deep venous thrombosis, angina, transient ischemic attack

Postmarketing reports: Myocardial infarction (MI)^[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 this drug 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]