Abacavir And Lamivudine
FDA Drug Information • Also known as: Abacavir And Lamivudine
- Brand Names
- Abacavir And Lamivudine
- Drug Class
- Hepatitis B Virus Nucleoside Analog Reverse Transcriptase Inhibitor [EPC], Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor [EPC]
- Route
- ORAL
- Dosage Form
- TABLET, FILM COATED
- Product Type
- HUMAN PRESCRIPTION DRUG
⚠ Boxed Warning (Black Box)
WARNING: HYPERSENSITIVITY REACTIONS 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 and lamivudine. 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 and lamivudine is 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 and lamivudine or reinitiation of therapy with abacavir and lamivudine, unless patients have a previously documented HLA-B*5701 allele assessment. Discontinue abacavir and lamivudine 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 and lamivudine, NEVER restart abacavir and lamivudine 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) ] . 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 human immunodeficiency virus (HIV-1) and have discontinued lamivudine, which is a component of abacavir and lamivudine. Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months in patients who discontinue abacavir and lamivudine and are co-infected with HIV-1 and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted [see Warnings and Precautions (5.2) ] . WARNING: HYPERSENSITIVITY REACTIONS and EXACERBATIONS OF HEPATITIS B See full prescribing information for complete boxed warning. Hypersensitivity Reactions ● Serious and sometimes fatal hypersensitivity reactions have occurred with abacavir-containing products. ( 5.1 ) ● Hypersensitivity to abacavir is a multi-organ clinical syndrome. ( 5.1 ) ● Patients who carry the HLA-B*5701 allele are at a higher risk of experiencing a hypersensitivity reaction to abacavir. ( 5.1 ) ● Abacavir and lamivudine is contraindicated in patients with a prior hypersensitivity reaction to abacavir and in HLA-B*5701-positive patients. ( 4 ) ● Discontinue abacavir and lamivudine as soon as a hypersensitivity reaction is suspected. Regardless of HLA-B*5701 status, permanently discontinue abacavir and lamivudine if hypersensitivity cannot be ruled out, even when other diagnoses are possible. ( 5.1 ) ● Following a hypersensitivity reaction to abacavir and lamivudine, NEVER restart abacavir and lamivudine or any other abacavir-containing product. ( 5.1 ) 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 human immunodeficiency virus (HIV-1) and have discontinued lamivudine, a component of abacavir and lamivudine. Monitor hepatic function closely in these patients and, if appropriate, initiate anti-hepatitis B treatment. ( 5.2 )
Description
11 DESCRIPTION Abacavir and Lamivudine Abacavir and lamivudine tablets, USP contain the following 2 synthetic nucleoside analogues: abacavir (ZIAGEN, also a component of TRIZIVIR) and lamivudine (also known as EPIVIR or 3TC) with inhibitory activity against HIV-1. Abacavir and lamivudine tablets, USP are for oral administration. Each orange colored, capsule-shaped, biconvex film coated tablet contains the active ingredients 600 mg of abacavir as abacavir sulfate USP and 300 mg of lamivudine USP, and the inactive ingredients magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The tablets are coated with a film (OPADRY orange YS-1-13065-A) that is made of FD&C Yellow No.6, hypromellose, polyethylene glycol 400, polysorbate 80, and titanium dioxide. Abacavir Sulfate, USP The chemical name of abacavir sulfate, USP is ( 1 S, 4R)- 4-[2-amino-6-(cyclopropylamino)-9 H -purin-9yl]-2-cyclopentene-1-methanol sulfate (salt) (2:1). Abacavir sulfate is the enantiomer with 1S , 4R absolute configuration on the cyclopentene ring. It has a molecular formula of (C 14 H 18 N 6 O) 2
What Is Abacavir And Lamivudine Used For?
1 INDICATIONS AND USAGE Abacavir and lamivudine tablets, in combination with other antiretroviral agents, are indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. Abacavir and lamivudine tablets, are combination of abacavir and lamivudine, both nucleoside analogue HIV-1 reverse transcriptase inhibitors, is indicated in combination with other antiretroviral agents for the treatment of HIV-1 infection. (1)
Dosage and Administration
2 DOSAGE AND ADMINISTRATION Before initiating abacavir and lamivudine tablets, screen for the HLA-B*5701 allele because abacavir and lamivudine tablets contain abacavir. (2.1) Adults: One tablet orally once daily. (2.2) Pediatric patients weighing at least 25 kg: One tablet daily. (2.3) Because abacavir and lamivudine tablet is a fixed-dose tablet and cannot be dose adjusted, abacavir and lamivudine tablets are not recommended in patients with creatinine clearance less than 30 mL per minute or patients with hepatic impairment. (2.4, 4) 2.1 Screening for HLA-B*5701 Allele Prior to Starting Abacavir and Lamivudine Tablets Screen for the HLA-B*5701 allele prior to initiating therapy with abacavir and lamivudine tablets [see Boxed Warning, Warnings and Precautions (5.1) ] . 2.2 Recommended Dosage for Adult Patients The recommended dosage of abacavir and lamivudine tablets for adults is one tablet taken orally once daily, in combination with other antiretroviral agents, with or without food. 2.3 Recommended Dosage for Pediatric Patients The recommended oral dose of abacavir and lamivudine tablets for pediatric patients weighing at least 25 kg is one tablet daily in combination with other antiretroviral agents [see Clinical Studies (14.2) ] . Before prescribing abacavir and lamivudine tablets, pediatric patients should be assessed for the ability to swallow tablets. 2.4 Not Recommended Due to Lack of Dosage Adjustment Because abacavir and lamivudine tablet is a fixed-dose tablet and cannot be dose adjusted, abacavir and lamivudine tablets are not recommended for: patients with creatinine clearance less than 30 mL per minute [see Use in Specific Populations (8.6) ] . patients with mild hepatic impairment. Abacavir and lamivudine tablets are contraindicated in patients with moderate or severe hepatic impairment [see Contraindications (4) , Use in Specific Populations (8.7) ] . Use of EPIVIR (lamivudine) oral solution or tablets and ZIAGEN (abacavir) oral solution may be considered.
Side Effects (Adverse Reactions)
6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Serious and sometimes fatal hypersensitivity reactions [see Boxed Warning, Warnings and Precautions (5.1) ] . Exacerbations of hepatitis B [see Boxed Warning, Warnings and Precautions (5.2) ] . Lactic acidosis and severe hepatomegaly with steatosis [see Warnings and Precautions (5.3) ] . Immune reconstitution syndrome [see Warnings and Precautions (5.4) ] . Myocardial infarction [see Warnings and Precautions (5.5) ] . The most commonly reported adverse reactions of at least moderate intensity (incidence greater than 5%) in an adult HIV-1 clinical trial were drug hypersensitivity, insomnia, depression/depressed mood, headache/migraine, fatigue/malaise, dizziness/vertigo, nausea, and diarrhea. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Laurus Generics Inc. at 1-833-3-LAURUS (1-833-352-8787) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience in Adult Subjects Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Serious and Fatal Abacavir-Associated Hypersensitivity Reactions In clinical trials, serious and sometimes fatal hypersensitivity reactions have occurred with abacavir, a component of abacavir and lamivudine [see Boxed Warning, Warnings and Precautions (5.1)]. These reactions have been characterized by 2 or more of the following signs or symptoms: (1) fever; (2) rash; (3) gastrointestinal symptoms (including nausea, vomiting, diarrhea, or abdominal pain); (4) constitutional symptoms (including generalized malaise, fatigue, or achiness); (5) respiratory symptoms (including dyspnea, cough, or pharyngitis). Almost all abacavir hypersensitivity reactions include fever and/or rash as part of the syndrome. Other signs and symptoms have included lethargy, headache, myalgia, edema, arthralgia, and paresthesia. Anaphylaxis, liver failure, renal failure, hypotension, adult respiratory distress syndrome, respiratory failure, myolysis, and death have occurred in association with these hypersensitivity reactions. Physical findings have included lymphadenopathy, mucous membrane lesions (conjunctivitis and mouth ulcerations), and maculopapular or urticarial rash (although some patients had other types of rashes and others did not have a rash). There were reports of erythema multiforme. Laboratory abnormalities included elevated liver chemistries, elevated creatine phosphokinase, elevated creatinine, and lymphopenia and abnormal chest x-ray findings (predominantly infiltrates, which were localized). Additional Adverse Reactions with Use of Abacavir and Lamivudine Therapy-Naive Adults: Treatment-emergent clinical adverse reactions (rated by the investigator as moderate or severe) with greater than or equal to 5% frequency during therapy with ZIAGEN 600 mg once daily or ZIAGEN 300 mg twice daily, both in combination with lamivudine 300 mg once daily and efavirenz 600 mg once daily, are listed in Table 1. Table 1. Treatment-Emergent (All Causality) Adverse Reactions of at Least Moderate Intensity (Grades 2 to 4, Greater than or Equal to 5% Frequency) in Therapy-Naive Adults (CNA30021) through 48 Weeks of Treatment a Subjects receiving ZIAGEN 600 mg once daily, experienced a significantly higher incidence of severe drug hypersensitivity reactions and severe diarrhea compared with subjects who received ZIAGEN 300 mg twice daily. Five percent (5%) of subjects receiving ZIAGEN 600 mg once daily had severe drug hypersensitivity reactions compared with 2% of subjects receiving ZIAGEN 300 mg twice daily. Two percent (2%) of subjects receiving ZIAGEN 600 mg once daily had severe diarrhea while none of the subjects receiving ZIAGEN 300 mg twice daily had this event. b CNA30024 was a...
Drug Interactions
7 DRUG INTERACTIONS Methadone: An increased methadone dose may be required in a small number of patients. (7.1) Sorbitol: Coadministration of lamivudine and sorbitol may decrease lamivudine concentrations; when possible, avoid chronic coadministration. (7.2) Riociguat: The riociguat dose may need to be reduced. (7.3) 7.1 Methadone In a trial of 11 HIV-1-infected subjects receiving methadone-maintenance therapy with 600 mg of ZIAGEN twice daily (twice the currently recommended dose), oral methadone clearance increased [see Clinical Pharmacology (12.3) ] . This alteration will not result in a methadone dose modification in the majority of patients; however, an increased methadone dose may be required in a small number of patients. 7.2 Sorbitol Coadministration of single doses of lamivudine and sorbitol resulted in a sorbitol dose-dependent reduction in lamivudine exposures. When possible, avoid use of sorbitol-containing medicines with lamivudine-containing medicines [see Clinical Pharmacology (12.3) ] . 7.3 Riociguat Coadministration with fixed-dose abacavir/dolutegravir/lamivudine resulted in increased riociguat exposure, which may increase the risk of riociguat adverse reactions [see Clinical Pharmacology (12.3) ] . The riociguat dose may need to be reduced. See full prescribing information for ADEMPAS (riociguat).
Contraindications
4 CONTRAINDICATIONS Abacavir and lamivudine 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) ] or lamivudine. with moderate or severe hepatic impairment [see Use in Specific Populations (8.7) ] . Presence of HLA-B*5701 allele. (4) Prior hypersensitivity reaction to abacavir or lamivudine. (4) Moderate or severe hepatic impairment. ( 4, 8.7)
Pregnancy and Breastfeeding
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to abacavir and lamivudine during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary Available data from the APR show no difference in the overall risk of birth defects for abacavir or lamivudine compared with the background rate for birth defects of 2.7% in the Metropolitan Atlanta Congenital Defects Program (MACDP) reference population (see Data) . The APR uses the MACDP as the U.S. reference population for birth defects in the general population. The MACDP evaluates women and infants from a limited geographic area and does not include outcomes for births that occurred at less than 20 weeks’ gestation. The rate of miscarriage is not reported in the APR. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15% to 20%. The background risk for major birth defects and miscarriage for the indicated population is unknown. In animal reproduction studies, oral administration of abacavir to pregnant rats during organogenesis resulted in fetal malformations and other embryonic and fetal toxicities at exposures 35 times the human exposure (AUC) at the recommended clinical daily dose. However, no adverse developmental effects were observed following oral administration of abacavir to pregnant rabbits during organogenesis, at exposures approximately 9 times the human exposure (AUC) at the recommended clinical dose. Oral administration of lamivudine to pregnant rabbits during organogenesis resulted in embryolethality at systemic exposure (AUC) similar to the recommended clinical dose; however, no adverse development effects were observed with oral administration of lamivudine to pregnant rats during organogenesis at plasma concentrations (C max ) 35 times the recommended clinical dose...
Overdosage
10 OVERDOSAGE There is no known specific treatment for overdose with abacavir and lamivudine. If overdose occurs, the patient should be monitored, and standard supportive treatment applied as required. Abacavir: It is not known whether abacavir can be removed by peritoneal dialysis or hemodialysis. Lamivudine: Because a negligible amount of lamivudine was removed via (4-hour) hemodialysis, continuous ambulatory peritoneal dialysis, and automated peritoneal dialysis, it is not known if continuous hemodialysis would provide clinical benefit in a lamivudine overdose event.
How Supplied
16 HOW SUPPLIED/STORAGE AND HANDLING Abacavir and lamivudine tablets, USP contain 600 mg of abacavir as abacavir sulfate USP and 300 mg of lamivudine USP. The tablets are orange colored, capsule-shaped, biconvex film coated tablets, debossed with “LT” on one side and plain on other side. They are packaged as follows: Bottles of 30 tablets NDC 42385-962-30 Bottles of 90 tablets NDC 42385-962-90 Bottles of 180 tablets NDC 42385-962-18 Store at 20° to 25°C (68° to 77°F), excursions permitted between 15° to 30°C (59° to 86°F). [see USP Controlled Room Temperature.]
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.