7822 7822 HIGHLIGHTS OF PRESCRIBING INFORMATION • Pediatric Patients Aged 3 Months and Older: • Before starting abacavir, review medical history for prior exposure to any abacavir-containing product. Table 4. Laboratory Abnormalities (Grades 3-4) in Therapy-naive Adults (CNA30024) through 48 Weeks MEDICATION GUIDE These highlights do not include all the information Administered either once or twice daily. Dose NEVER restart abacavir or any other abacavir-containing product following a hypersensitivity reaction to of Treatment should be calculated on body weight (kg) and abacavir, regardless of HLA-B*5701 status. needed to use ABACAVIR TABLETS safely and Abacavir plus Zidovudine plus should not exceed 600 mg daily. (2.3) • To reduce the risk of a life-threatening hypersensitivity reaction, regardless of HLA-B*5701 status, Grade 3/4 Abacavir tablets USP 300 mg effectively. See full prescribing information for Lamivudine plus Efavirenz Lamivudine plus Efavirenz • Patients with Hepatic Impairment: Mild hepatic discontinue abacavir immediately if a hypersensitivity reaction is suspected, even when other diagnoses Laboratory Abnormalities ABACAVIR TABLETS. (n=324) (n=325) (A bak a vir) impairment – 200 mg twice daily. (2.4) are possible (e.g., acute onset respiratory diseases such as pneumonia, bronchitis, pharyngitis, or ′ ABACAVIR tablets, for oral use influenza; gastroenteritis; or reactions to other medications). Elevated CPK (>4 X ULN) 8% 8% -----------DOSAGE FORMS AND STRENGTHS--------- Initial U.S. Approval 1998 • If a hypersensitivity reaction cannot be ruled out, do not restart abacavir or any other abacavir containing Elevated ALT (>5 X ULN) 6% 6% What is the most important information I should know about abacavir • Tablets: 300 mg scored (3) products because more severe symptoms which may include life-threatening hypotension and death can WARNING: HYPERSENSITIVITY REACTIONS Elevated AST (>5 X ULN) 6% 5% tablets? occur within hours. See full prescribing information for complete ----------------CONTRAINDICATIONS------------------ • If a hypersensitivity reaction is ruled out, patients may restart abacavir. Rarely, patients who have stopped Hypertriglyceridemia(>750 mg/dL) 6% 5% Abacavir tablets can cause serious side effects, including: boxed warning. • Presence of HLA-B*5701 allele. (4) abacavir for reasons other than symptoms of hypersensitivity have also experienced life-threatening • Serious and sometimes fatal hypersensitivity • Prior hypersensitivity reaction to abacavir. (4) Hyperamylasemia (>2 X ULN) 4% 5% • Serious allergic reaction (hypersensitivity reaction) that can reactions within hours of reinitiating abacavir therapy. Therefore, reintroduction of abacavir or any other reactions have occurred with abacavir • Moderate or severe hepatic impairment. (4) Neutropenia (ANC <750/mm3) 2% 4% abacavir-containing product is recommended only if medical care can be readily accessed. cause death have happened with abacavir tablets and other tablets 300 mg. (5.1) -----------WARNINGS AND PRECAUTIONS------------ • A Medication Guide and Warning Card that provide information about recognition of hypersensitivity Anemia (Hgb ≤ 6.9 gm/dL) <1% 2% • Hypersensitivity to abacavir is a multi- abacavir-containing products. Your risk of this allergic reaction is • Lactic acidosis and severe hepatomegaly with reactions should be dispensed with each new prescription and refill. 3 organ clinical syndrome. (5.1) Thrombocytopenia (Platelets < 50,000/ mm ) 1% <1% * steatosis, including fatal cases, have been much higher if you have a gene variation called HLA-B 5701. • Patients who carry the HLA-B*5701 allele 5.2 Lactic Acidosis and Severe Hepatomegaly with Steatosis Leukopenia (WBC ≤ 1,500/mm3) <1% 2% reported with the use of nucleoside analogues. are at higher risk for experiencing a Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of Your healthcare provider can determine with a blood test if you have (5.2) ULN = Upper limit of normal. hypersensitivity reaction to abacavir. (5.1) nucleoside analogues, including abacavir. A majority of these cases have been in women. Female sex and obesity • Immune reconstitution syndrome has been this gene variation. • Abacavir is contraindicated in patients may be risk factors for the development of lactic acidosis and severe hepatomegaly with steatosis in patients n = Number of subjects assessed. reported in patients treated with combination with a prior hypersensitivity reaction to treated with antiretroviral nucleoside analogues. Treatment with Abacavir tablets should be suspended in any antiretroviral therapy. (5.3) Laboratory abnormalities in CNA3005 are listed in Table 5. If you get a symptom from 2 or more of the following groups while abacavir and in HLA-B*5701-positive patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity, taking abacavir tablets, call your healthcare provider right away to patients. (4) ------------------ADVERSE REACTIONS----------------- which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations. Table 5. Treatment-emergent Laboratory Abnormalities (Grades 3-4) in CNA3005 • Discontinue abacavir tablets 300 mg as • The most commonly reported adverse Abacavir plus Lamivudine/ Indinavir plus Lamivudine/ find out if you should stop taking Abacavir tablets. 5.3 Immune Reconstitution Syndrome soon as a hypersensitivity reaction is reactions of at least moderate intensity Grade 3/4 Laboratory Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, Zidovudine Zidovudine suspected. Regardless of HLA-B*5701 (incidence greater than or equal to 10%) in adult Abnormalities Symptom(s) including abacavir. During the initial phase of combination antiretroviral treatment, patients whose immune (n=262) (n=264) status, permanently discontinue abacavir HIV-1 clinical trials were nausea, headache, systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such Elevated CPK (>4 x ULN) 18 (7%) 18 (7%) tablets 300 mg if hypersensitivity cannot be malaise and fatigue, nausea and vomiting, Group 1 Fever as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jirovecii pneumonia [PCP], or tuberculosis), 7822 ruled out, even when other diagnoses are and dreams/sleep disorders. (6.1) ALT (>5.0 x ULN) 16 (6%) 16 (6%) possible. (5.1) which may necessitate further evaluation and treatment. Group 2 Rash • The most commonly reported adverse Neutropenia (<750/mm3) 13 (5%) 13 (5%) • Following a hypersensitivity reaction to reactions of at least moderate intensity Autoimmune disorders ( such as Graves’ disease, polymyositis, and Guillain- Barré syndrome) have also been Group 3 Nausea, vomiting, diarrhea, abdominal (stomach area) pain abacavir, NEVER restart abacavir tablets (incidence greater than or equal to 5%) in reported to occur in the setting of immune reconstitution, however, the time to onset is more variable and can Hypertriglyceridemia (>750 mg/dL) 5 (2%) 3 (1%) 300 mg or any other abacavir-containing pediatric HIV-1 clinical trials were fever and/or occur many months after initiation of treatment. Hyperamylasemia (>2.0 x ULN) 5 (2%) 1 (<1%) Group 4 Generally ill feeling, extreme tiredness, or achiness product. (5.1) chills, nausea and vomiting, skin rashes, and Hyperglycemia (>13.9 mmol/L) 2 (<1%) 2 (<1%) Group 5 Shortness of breath, cough, sore throat ear/nose/throat infections. (6.2) 5.4 Myocardial Infarction ------------RECENT MAJOR CHANGES----------------- Several prospective, observational, epidemiological studies have reported an association with the use of Anemia (Hgb ≤6.9 g/dL) 0 (0%) 3 (1%) Boxed Warning To report SUSPECTED ADVERSE REACTIONS, abacavir and the risk of myocardial infarction (MI). Meta-analyses of randomized, controlled, clinical trials have A list of these symptoms is on the Warning Card your pharmacist gives you. Warnings and Precautions, Lactic Acidosis and Severe contact Strides Pharma Inc. at 1-877-244-9825 observed no excess risk of MI in abacavir-treated subjects as compared with control subjects. To date, there ULN = Upper limit of normal. or www.strides.com or FDA at 1-800-FDA-1088 or Hepatomegaly with Steatosis (5.2) 05/2018 is no established biological mechanism to explain a potential increase in risk. In totality, the available data from n = Number of subjects assessed. Carry this Warning Card with you at all times. Warnings and Precautions, Fat Redistribution www.fda.gov/medwatch. the observational studies and from controlled clinical trials show inconsistency; therefore, evidence for a causal The frequencies of treatment-emergent laboratory abnormalities were comparable between treatment groups (previous 5.4) Removed 05/2018 relationship between abacavir treatment and the risk of MI is inconclusive If you stop abacavir tablets because of an allergic reaction, never -----------------DRUG INTERACTIONS------------------ Warnings and Precautions, Myocardial Infarction (5.4) in CNA30021. • Methadone: An increased methadone dose may As a precaution, the underlying risk of coronary heart disease should be considered when prescribing antiretroviral take abacavir tablets or any other abacavir-containing medicine 05/2018 be required in a small number of patients. (7.1) therapies, including abacavir, and action taken to minimize all modifiable risk factors (e.g., hypertension, 6.2 Clinical Trials Experience