Abacavir and lamivudine

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

• interferon or ribavirin (to treat hepatitis C);

• methadone; or

• any other HIV medicines.

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

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine may raise the chance of heart attack. Talk with the doctor.
• Use care if you have risks for heart disease (high blood pressure, high cholesterol, overweight, high blood sugar or diabetes, cigarette smoking, man older than 40 years of age, other family members with early heart disease, woman after change of life). Talk with your doctor.
• If abacavir and lamivudine is stopped because you have an allergy to it, do not restart it. It may not be safe to restart this medicine. Throw away any of abacavir and lamivudine that you have not taken. If you are not sure how to throw away unused drugs, check with your pharmacist.
• If this medicine is stopped for any other reason, do not restart it without talking to the doctor. It could be very risky to restart on your own.
• Do not run out of abacavir and lamivudine.
• Talk with your doctor before you drink alcohol.
• This medicine is not a cure for HIV. Stay under the care of your doctor.
• This medicine does not stop the spread of diseases like HIV or hepatitis that are passed through blood or having sex. Do not have any kind of sex without using a latex or polyurethane condom. Do not share needles or other things like toothbrushes or razors. Talk with your doctor.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.

• Store at room temperature.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

• Epzicom

HIV-1 treatment: Oral: One tablet (abacavir 600 mg and lamivudine 300 mg) once daily. Note: Abacavir/lamivudine is a component of a recommended initial regimen with dolutegravir for ART treatment-naive patients who are HLA B*5701 negative (HHS [adult] 2015).

More frequently reported side effects include: hypersensitivity reaction. See below for a comprehensive list of adverse effects.

Applies to abacavir / lamivudine: oral tablet

General

In 1 study, once- or twice-daily abacavir was used in combination with lamivudine and efavirenz. Patients receiving once-daily abacavir 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

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]

Abacavir and lamivudine:
-Common (1% to 10%): Drug hypersensitivity
-Postmarketing reports: Sensitization reactions (including anaphylaxis)

Abacavir:
-Common (1% to 10%): Hypersensitivity reactions (including fever, rash [maculopapular, urticarial], nausea, vomiting, diarrhea, abdominal pain, pharyngitis, malaise, fatigue, 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)

Lamivudine:
-Frequency not reported: Anaphylactoid reactions[Ref]

Hepatic

Abacavir and lamivudine:
-Common (1% to 10%): Elevated ALT, elevated AST
-Uncommon (0.1% to 1%): Abnormal bilirubin
-Frequency not reported: Severe hepatomegaly with steatosis
-Postmarketing reports: Hepatic steatosis, posttreatment exacerbation of hepatitis B

Abacavir:
-Frequency not reported: Liver function test abnormalities, elevated GGT

Lamivudine:
-Uncommon (0.1% to 1%): Transient elevations in liver enzymes (AST, ALT)
-Rare (less than 0.1%): Hepatitis
-Frequency not reported: Elevated bilirubin, elevated hepatic enzymes, hepatic decompensation, severe acute exacerbations of hepatitis[Ref]

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 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.[Ref]

Gastrointestinal

Abacavir and lamivudine:
-Common (1% to 10%): Nausea, diarrhea, abdominal pain/gastritis, abnormal amylase
-Postmarketing reports: Stomatitis

Abacavir:
-Common (1% to 10%): Nausea, vomiting, diarrhea
-Postmarketing reports: Pancreatitis (rare)

Lamivudine:
-Common (1% to 10%): Nausea, vomiting, abdominal pain/cramps, diarrhea
-Frequency not reported: Elevated lipase
-Postmarketing reports: Elevated serum amylase (rare), pancreatitis (rare)[Ref]

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

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.[Ref]

Abacavir and lamivudine:
-Common (1% to 10%): Rash
-Postmarketing reports: Alopecia, erythema multiforme, Stevens-Johnson syndrome, urticaria

Abacavir:
-Frequency not reported: Sweet's syndrome
-Postmarketing reports: Rash without systemic symptoms (common), erythema multiforme (very rare), Stevens-Johnson syndrome (very rare), toxic epidermal necrolysis (very rare)

Lamivudine:
-Common (1% to 10%): Rash
-Rare (less than 0.1%): Angioedema
-Frequency not reported: Pruritus, urticaria
-Postmarketing reports: Alopecia (common)[Ref]

Hematologic

Abacavir and lamivudine:
-Common (1% to 10%): Abnormal absolute neutrophils
-Uncommon (0.1% to 1%): Abnormal hemoglobin, abnormal platelets, abnormal WBC
-Postmarketing reports: Aplastic anemia, anemia (including pure red cell aplasia and severe anemias progressing on therapy), lymphadenopathy, splenomegaly

Abacavir:
-Frequency not reported: Anemia, neutropenia, agranulocytosis

Lamivudine:
-Uncommon (0.1% to 1%): Thrombocytopenia, neutropenia, anemia
-Postmarketing reports: Pure red cell aplasia (very rare)[Ref]

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

Occasionally, neutropenia and anemia reported with lamivudine were severe.[Ref]

Nervous system

Abacavir and lamivudine:
-Common (1% to 10%): Headache/migraine, dizziness/vertigo
-Postmarketing reports: Peripheral neuropathy, paresthesia, seizures

Abacavir:
-Common (1% to 10%): Headache

Lamivudine:
-Common (1% to 10%): Headache
-Postmarketing reports: Paresthesia (very rare), peripheral neuropathy (very rare)[Ref]

Other

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

Abacavir and lamivudine:
-Common (1% to 10%): Fatigue/malaise, pyrexia
-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)[Ref]

Psychiatric

Abacavir and lamivudine:
-Common (1% to 10%): Insomnia, depression/depressed mood, abnormal dreams, anxiety

Lamivudine:
-Common (1% to 10%): Insomnia[Ref]

Metabolic

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]

Abacavir and lamivudine:
-Common (1% to 10%): Abnormal triglycerides
-Uncommon (0.1% to 1%): Abnormal alkaline phosphatase, abnormal glucose, abnormal sodium
-Frequency not reported: Lactic acidosis
-Postmarketing reports: Hyperglycemia, redistribution/accumulation of body fat

Abacavir:
-Common (1% to 10%): Anorexia
-Frequency not reported: Elevated blood glucose, elevated triglycerides
-Postmarketing reports: Hyperlactatemia (common), lactic acidosis (rare)

Lamivudine:
-Postmarketing reports: Hyperlactatemia (common), lactic acidosis (rare)

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]

Musculoskeletal

Abacavir and lamivudine:
-Uncommon (0.1% to 1%): Abnormal creatine phosphokinase (CPK)
-Postmarketing reports: Muscle weakness, CPK elevation, rhabdomyolysis

Abacavir:
-Frequency not reported: Elevated CPK

Lamivudine:
-Postmarketing reports: Arthralgia (common), muscle disorders (common), rhabdomyolysis (rare)

Combination antiretroviral therapy:
-Frequency not reported: Osteonecrosis[Ref]

Cardiovascular

Abacavir:
-Postmarketing reports: Myocardial infarction (MI)

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.

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

Abacavir and lamivudine:
-Uncommon (0.1% to 1%): Abnormal creatinine[Ref]

Respiratory

Abacavir and lamivudine:
-Postmarketing reports: Abnormal breath sounds/wheezing

Lamivudine:
-Common (1% to 10%): Cough, nasal symptoms[Ref]

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

US CDC recommendations: 1 tablet orally once a day
Duration of therapy: 28 days

Comments:
-Recommended as part of alternative regimens (NNRTI-based, protease inhibitor-based, or triple NRTI) for nonoccupational postexposure prophylaxis of HIV infection
-Prophylaxis should be started as soon as possible, within 72 hours of exposure.
-Current guidelines should be consulted for additional information.

Mild liver dysfunction (Child-Pugh A): Not recommended; individual components should be used.
Moderate or severe liver dysfunction (Child-Pugh B or C): Contraindicated

Administration advice:
-Use in combination with other antiretroviral agents.
-May administer without regard to food
-Consult the manufacturer product information regarding missed doses.

General:
-Screening for HLA-B*5701 allele recommended before starting this drug.
-Before starting this drug, medical history should be reviewed for prior exposure to any abacavir-containing product (to prevent reintroduction in patient with history of abacavir hypersensitivity).

Monitoring:
-Hepatic: Hepatic function of HIV-1/HBV-coinfected patients with clinical and laboratory follow-up (for at least several months after stopping therapy)

Patient advice:
-Always read the Medication Guide and Warning Card (with information about abacavir hypersensitivity reaction) dispensed with each new and refill prescription; carry the Warning Card.
-Contact physician immediately if signs/symptoms of hypersensitivity develop; do not restart this or any other abacavir-containing product after a hypersensitivity reaction.
-If this drug is stopped for any reason besides hypersensitivity, do not restart it (or any other abacavir-containing product) without consulting physician; medical care must be readily accessible.