Abacavir

Name: Abacavir

What should I discuss with my healthcare provider before taking abacavir?

You should not use abacavir if you have had an allergic reaction to any medicine that contains abacavir (Ziagen, Epzicom, Triumeq, or Trizivir).

Abacavir can also cause severe or life-threatening effects on your liver. You should not take abacavir if you have moderate or severe liver disease.

Many combination HIV medicines have abacavir as an ingredient. Ziagen should not be taken together with any other medicine that contains abacavir.

Some people taking abacavir develop a serious condition called lactic acidosis. This may be more likely in women, in people who are overweight or have liver disease, and in people who have taken HIV/AIDS medication for a long time. Talk with your doctor about your risk.

To make sure abacavir is safe for you, tell your doctor if you have:

  • heart disease, high blood pressure;

  • a gene variation called HLA-B*5701 allele (your doctor will test you for this);

  • liver disease;

  • a risk factor for heart disease such as smoking, diabetes, or high cholesterol; or

  • if you have used any other HIV medication in the past.

It is not known whether abacavir will harm an unborn baby. HIV can be passed to your baby if you are not properly treated during pregnancy. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Take all of your HIV medicines as directed to control your infection.

If you are pregnant, your name may be listed on a pregnancy registry. This is to track the outcome of the pregnancy and to evaluate any effects of abacavir on the baby.

Women with HIV or AIDS should not breast feed a baby. Even if your baby is born without HIV, the virus may be passed to the baby in your breast milk.

Pharmacology

Nucleoside reverse transcriptase inhibitor. Abacavir is a guanosine analogue which is phosphorylated to carbovir triphosphate which interferes with HIV viral RNA-dependent DNA polymerase resulting in inhibition of viral replication.

Absorption

Rapid and extensive absorption

Distribution

Vd: 0.86 ± 0.15 L/kg; CSF to plasma AUC ratio: 27% to 33%

Metabolism

Hepatic via alcohol dehydrogenase and glucuronyl transferase to inactive carboxylate and glucuronide metabolites; not significantly metabolized by cytochrome P450 enzymes; intracellulary metabolized to carbovir triphosphate.

Excretion

Urine: ~83% (1.2% as unchanged drug, 30% as 5'-carboxylic acid metabolite, 36% as the glucuronide, and 15% as other metabolites); feces (16% total dose)

Clearance (apparent): Single dose 8 mg/kg (Hughes 1999): Pediatric patients ≥3 months to ≤13 years: 17.84 mL/minute/kg; Adults: 10.14 mL/minute/kg

Time to Peak

Pediatric patients ≥3 months to ≤13 years: Within 1.5 hours (Hughes 1999); Adults: 0.7 to 1.7 hours

Half-Life Elimination

Serum:

Pediatric patients ≥3 months to ≤13 years: 1 to 1.5 hours (Hughes 1999; Kline 1999)

Adults: 1.54 ± 0.63 hours

Hepatic impairment (mild): Increases half-life by 58%

Intracellular: 12 to 26 hours

Protein Binding

50%

Special Populations Hepatic Function Impairment

In mild hepatic impairment (Child-Pugh score 5 to 6), AUC increased 89%.

Contraindications

Hypersensitivity to abacavir or any component of the formulation; patients who are positive for the HLA-B*5701 allele; moderate to severe hepatic impairment

Dosing Adult

HIV-1 infection, treatment: Oral: 300 mg twice daily or 600 mg once daily in combination with other antiretroviral agents.

Dosing Geriatric

Refer to adult dosing.

Abacavir Interactions

Avoid drinking alcohol. It may increase your risk of liver damage.

Taking this medicine will not prevent you from passing HIV to other people. Do not have unprotected sex or share razors or toothbrushes. Talk with your doctor about safe ways to prevent HIV transmission during sex. Sharing drug or medicine needles is never safe, even for a healthy person.

Tell your doctor about all your current medicines and any you start or stop using, especially:

  • methadone; or
  • any other HIV medicines.

This list is not complete. Other drugs may interact with abacavir, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Which drugs or supplements interact with abacavir?

Alcohol competes with abacavir for elimination from the body. Therefore, alcohol consumption may increase the concentration of abacavir in the body, and this could lead to increased frequency or severity of side effects from abacavir. Abacavir does not affect the elimination of alcohol.

Abacavir Interactions

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

  • Methadone
  • Epzicom (abacavir sulfate and lamivudine) and Trizivir (abacavir sulfate, lamivudine, and zidovudine).

This is not a complete list of abacavir drug interactions. Ask your doctor or pharmacist for more information.

Abacavir and Lactation

Do not breastfeed while receiving this medication. It is not known if abacavir can be passed to your baby in your breast milk and whether it could harm your baby. Also, mothers with HIV should not breastfeed because HIV can be passed to the baby in the breast milk.

Abacavir Overdose

If you take too much abacavir, call your doctor or poison control center right away.

If abacavir is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

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 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 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

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]

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 hypersensitivity could not be ruled out.[Ref]

Metabolic

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]

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]

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

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]

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]

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

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]

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]

Some side effects of abacavir may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Usual Pediatric Dose for HIV Infection

3 months or older:
Oral solution: 8 mg/kg orally twice a day or 16 mg/kg orally once a day
Maximum dose: 600 mg/day

Tablets:
14 to less than 20 kg: 150 mg orally twice a day or 300 mg orally once a day
20 to less than 25 kg: 150 mg orally in the morning and 300 mg in the evening, or 450 mg orally once a day
25 kg or more: 300 mg orally twice a day or 600 mg orally once a day

Use: In combination with other antiretroviral agents, for the treatment of HIV-1 infection

Dialysis

Data not available

Abacavir Pregnancy Warnings

This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus. AU TGA pregnancy category: B3 US FDA pregnancy category: Not assigned. Risk summary: Malformative risk with use of this drug in pregnant women is unlikely. Comments: A pregnancy exposure registry is available.

Animal studies (high-dose) have revealed evidence of embryonic and fetal toxicity, including developmental toxicity, fetal anasarca, skeletal malformations, and increased incidence of stillbirth. Placental transfer has been observed in humans. There are no controlled data in human pregnancy; however, based on observed outcomes (more than 800 after first-trimester exposure and more than 1000 after second-/third-trimester exposure), the malformative risk is unlikely in humans. To monitor maternal-fetal outcome of pregnant women exposed to antiretroviral therapy, an Antiretroviral Pregnancy Registry (APR) has been established. Healthcare providers are encouraged to prospectively register patients. For additional information: apregistry.com The APR has received prospective reports of over 2000 exposures to this drug (over 900 exposed in the first trimester) resulting in live births; there was no difference between abacavir and overall birth defects compared with the background birth defect rate of 2.7% in the reference population. The prevalence of defects in the first trimester was 3% for abacavir. No increased risk of major birth defects observed for this drug compared to background rate. AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans. US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decision and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

Administrative Information

LactMed Record Number

656

Last Revision Date

20170110

Disclaimer

Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

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