ABACAVIR, LAMIVUDINE AND ZIDOVUDINE

ABACAVIR, LAMIVUDINE AND ZIDOVUDINE- lamivudine, zidovudine and abacavir sulfate tablet
Lupin Pharmaceuticals, Inc.

WARNING: HYPERSENSITIVITY REACTIONS, HEMATOLOGIC TOXICITY, MYOPATHY, LACTIC ACIDOSIS AND SEVERE HEPATOMEGALY WITH STEATOSIS, and EXACERBATIONS OF HEPATITIS B

Hypersensitivity Reactions

Serious and sometimes fatal hypersensitivity reactions, with multiple organ involvement, have occurred with abacavir, a component of abacavir, lamivudine and zidovudine tablets. Patients who carry the HLA-B*5701 allele are at a higher risk of a hypersensitivity reaction to abacavir; although, hypersensitivity reactions have occurred in patients who do not carry the HLA-B*5701 allele [see WARNINGS AND PRECAUTIONS (5.1)].

Abacavir, lamivudine and zidovudine tablets are contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA-B*5701-positive patients [see CONTRAINDICATIONS (4), WARNINGS AND PRECAUTIONS (5.1)]. All patients should be screened for the HLA-B*5701 allele prior to initiating therapy with abacavir, lamivudine and zidovudine tablets or reinitiation of therapy with abacavir, lamivudine and zidovudine tablets, unless patients have a previously documented HLA-B*5701 allele assessment. Discontinue abacavir, lamivudine and zidovudine tablets immediately if a hypersensitivity reaction is suspected, regardless of HLA-B*5701 status and even when other diagnoses are possible [see CONTRAINDICATIONS (4), WARNINGS AND PRECAUTIONS (5.1)].

Following a hypersensitivity reaction to abacavir, lamivudine and zidovudine tablets, NEVER restart abacavir, lamivudine and zidovudine tablets or any other abacavir-containing product because more severe symptoms, including death, can occur within hours. Similar severe reactions have also occurred rarely following the reintroduction of abacavir-containing products in patients who have no history of abacavir hypersensitivity [see WARNINGS AND PRECAUTIONS (5.1)].

Hematologic Toxicity

Zidovudine, a component of abacavir, lamivudine and zidovudine tablets, has been associated with hematologic toxicity, including neutropenia and severe anemia, particularly in patients with advanced Human Immunodeficiency Virus (HIV-1) disease [see WARNINGS AND PRECAUTIONS (5.2)].

Myopathy

Prolonged use of zidovudine has been associated with symptomatic myopathy [see WARNINGS AND PRECAUTIONS (5.3)].

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues, including abacavir, lamivudine, and zidovudine (components of abacavir, lamivudine and zidovudine tablets). Discontinue abacavir, lamivudine and zidovudine tablets if clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity occur [see WARNINGS AND PRECAUTIONS (5.4)].

Exacerbations of Hepatitis B

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, a component of abacavir, lamivudine and zidovudine tablets. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue abacavir, lamivudine and zidovudine tablets and are co-infected with HIV-1 and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted [see WARNINGS AND PRECAUTIONS (5.5)].

1 INDICATIONS AND USAGE

Abacavir, lamivudine and zidovudine tablet is indicated in combination with other antiretrovirals or alone for the treatment of human immunodeficiency virus type 1 (HIV-1) infection.

Limitations of Use:

  • Limited data exist on the use of abacavir, lamivudine and zidovudine tablets alone in patients with higher baseline viral load levels (greater than 100,000 copies per mL) [see CLINICAL STUDIES (14)].

2 DOSAGE AND ADMINISTRATION

2.1 Screening for HLA-B*5701 Allele prior to Starting Abacavir, Lamivudine and Zidovudine Tablets

Screen for the HLA-B*5701 allele prior to initiating therapy with abacavir, lamivudine and zidovudine tablets [see BOXED WARNING, WARNINGS AND PRECAUTIONS (5.1)].

2.2 Recommended Dosage for Adults and Pediatric Patients Weighing at Least 40 kg

The recommended dosage of abacavir, lamivudine and zidovudine tablet is one tablet taken orally twice daily with or without food.

2.3 Not Recommended Due to Lack of Dosage Adjustment

Because abacavir, lamivudine and zidovudine tablet is a fixed-dose tablet and cannot be dose adjusted, abacavir, lamivudine and zidovudine tablet is not recommended for:

  • pediatric patients who weigh less than 40 kg [see USE IN SPECIFIC POPULATIONS (8.4)].
  • patients with creatinine clearance less than 50 mL per minute [see USE IN SPECIFIC POPULATIONS (8.6)].
  • patients with mild hepatic impairment. Abacavir, lamivudine and zidovudine tablet is contraindicated in patients with moderate or severe hepatic impairment [see CONTRAINDICATIONS (4), USE IN SPECIFIC POPULATIONS (8.7)].

3 DOSAGE FORMS AND STRENGTHS

Abacavir, lamivudine and zidovudine tablets contain 300 mg of abacavir as abacavir sulfate, 150 mg of lamivudine, and 300 mg of zidovudine. The tablets are blue-green colored, oval shaped, biconvex, film-coated, debossed with “LU” on one side and “N51” on the other side.

4 CONTRAINDICATIONS

Abacavir, lamivudine and zidovudine tablets are contraindicated in patients:

  • who have the HLA-B*5701 allele [see WARNINGS AND PRECAUTIONS (5.1)].
  • with prior hypersensitivity reaction to abacavir [see WARNINGS AND PRECAUTIONS (5.1)], lamivudine, or zidovudine.
  • with moderate or severe hepatic impairment [see USE IN SPECIFIC POPULATIONS (8.7)].

5 WARNINGS AND PRECAUTIONS

5.1 Hypersensitivity Reactions

Serious and sometimes fatal hypersensitivity reactions have occurred with abacavir, a component of abacavir, lamivudine and zidovudine tablets. These hypersensitivity reactions have included multi-organ failure and anaphylaxis and typically occurred within the first 6 weeks of treatment with abacavir (median time to onset was 9 days); although abacavir hypersensitivity reactions have occurred any time during treatment [see ADVERSE REACTIONS (6.1)]. Patients who carry the HLA-B*5701 allele are at a higher risk of abacavir hypersensitivity reactions; although, patients who do not carry the HLA-B*5701 allele have developed hypersensitivity reactions. Hypersensitivity to abacavir was reported in approximately 206 (8%) of 2,670 patients in 9 clinical trials with abacavir-containing products where HLA-B*5701 screening was not performed. The incidence of suspected abacavir hypersensitivity reactions in clinical trials was 1% when subjects carrying the HLA-B*5701 allele were excluded. In any patient treated with abacavir, the clinical diagnosis of hypersensitivity reaction must remain the basis of clinical decision making.

Due to the potential for severe, serious, and possibly fatal hypersensitivity reactions with abacavir:

  • All patients should be screened for the HLA-B*5701 allele prior to initiating therapy with abacavir, lamivudine and zidovudine tablets or reinitiation of therapy with abacavir, lamivudine and zidovudine tablets, unless patients have a previously documented HLA-B*5701 allele assessment.
  • Abacavir, lamivudine, and zidovudine tablets are contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA-B*5701-positive patients.
  • Before starting abacavir, lamivudine and zidovudine tablets, review medical history for prior exposure to any abacavir-containing product. NEVER restart abacavir, lamivudine and zidovudine tablets or any other abacavir-containing product following a hypersensitivity reaction to abacavir, regardless of HLA-B*5701 status.
  • To reduce the risk of a life-threatening hypersensitivity reaction, regardless of HLA-B*5701 status, discontinue abacavir, lamivudine and zidovudine tablets immediately if a hypersensitivity reaction is suspected, even when other diagnoses are possible (e.g., acute onset respiratory diseases such as pneumonia, bronchitis, pharyngitis, or influenza; gastroenteritis; or reactions to other medications).
  • If a hypersensitivity reaction cannot be ruled out, do not restart abacavir, lamivudine and zidovudine tablets or any other abacavir-containing products because more severe symptoms, which may include life-threatening hypotension and death, can occur within hours.
  • If a hypersensitivity reaction is ruled out, patients may restart abacavir, lamivudine and zidovudine tablets. Rarely, patients who have stopped abacavir for reasons other than symptoms of hypersensitivity have also experienced life-threatening reactions within hours of reinitiating abacavir therapy. Therefore, reintroduction of abacavir, lamivudine and zidovudine tablets or any other abacavir-containing product is recommended only if medical care can be readily accessed.
  • A Medication Guide and Warning Card that provide information about recognition of abacavir hypersensitivity reactions should be dispensed with each new prescription and refill.

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