Abacavir Sulfate / Lamivudine

Pronunciation: (a-BAK-a-vir SUL-fate/la-MIV-ue-deen)Class: Nucleoside analog reverse transcriptase inhibitor combination

Trade Names:Epzicom- Tablets abacavir 600 mg (as sulfate)/lamivudine 300 mg

Pharmacology

Inhibits replication of HIV by incorporating into HIV DNA and producing incomplete, nonfunctional DNA.

Indications and Usage

Treatment of HIV-1 infection in combination with other antiretroviral agents.

Contraindications

Hypersensitivity to any component of product; hepatic function impairment.

Dosage and Administration

Adults

PO 1 tablet daily (abacavir sulfate 600 mg/lamivudine 300 mg), in combination with other antiretroviral agents.

General Advice

• May be taken with or without food.

Storage/Stability

Store at 59° to 86°F.

Drug Interactions

Ethanol

Ethanol decreases the elimination of abacavir, causing an increase in overall exposure.

Interferon alfa

Hepatic decomposition (some fatal) has occurred in HIV-1/HCV coinfected patients receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin.

Methadone

Methadone Cl increased 22% during coadministration. Methadone may delay the absorption of abacavir/lamivudine, resulting in a decrease in bioavailability.

Ribavirin

Ribavirin may reduce the phosphorylation of lamivudine.

Trimethoprim/Sulfamethoxazole

Lamivudine serum levels may be elevated, increasing the pharmacologic and adverse effects.

Zalcitabine

Lamivudine and zalcitabine may inhibit the intracellular phosphorylation of one another.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

MI (postmarketing).

CNS

Insomnia (9%); fatigue/malaise (8%); depression/depressed mood, headache/migraine (7%); dizziness/vertigo (6%); abnormal dreams, anxiety (5%); paresthesia, peripheral neuropathy, seizures (postmarketing).

Dermatologic

Rash (5%); alopecia, erythema multiforme, Stevens-Johnson syndrome, TEN (postmarketing).

GI

Diarrhea, nausea (6%); abdominal pain/gastritis (5%); pancreatitis, stomatitis (postmarketing).

Hematologic-Lymphatic

Anemia including pure red cell aplasia and severe anemia progressing with therapy, aplastic anemia, lymphadenopathy, splenomegaly (postmarketing).

Hepatic

Lactic acidosis and hepatic steatosis, posttreatment exacerbation of hepatitis B (postmarketing).

Hypersensitivity

Drug hypersensitivity (9%); sensitization reactions (including anaphylaxis), urticaria (postmarketing).

Lab Tests

Anemia; elevation of bilirubin, amylase, and lipase levels; elevations of blood glucose and triglycerides; LFT abnormalities; neutropenia; thrombocytopenia.

Metabolic

Hyperglycemia (postmarketing).

Musculoskeletal

CPK elevation, muscle weakness, rhabdomyolysis (postmarketing).

Respiratory

Abnormal breath sounds/wheezing (postmarketing).

Miscellaneous

Pyrexia (5%); redistribution/accumulation of body fat, weakness (postmarketing).

Precautions

Warnings Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir. The hypersensitivity reaction is a multiorgan syndrome usually characterized by signs or symptoms in 2 or more of the following groups: fever, rash, GI (eg, abdominal pain, nausea, vomiting), constitutional (eg, aches, fatigue, malaise), and respiratory (eg, cough, dyspnea, pharyngitis). Permanently discontinue if hypersensitivity reaction occurs. Patients carrying the HLA-B∗5710 allele are at a high risk for experiencing a hypersensitivity reaction to abacavir. Do not restart any abacavir-containing product following a hypersensitivity reaction. Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, may occur. Severe acute exacerbation of hepatitis B has been reported in patient coinfected with hepatitis B virus (HBV) and HIV-1 and who have discontinued lamivudine. Closely monitor hepatic function for at least several months after discontinuation of abacavir/lamivudine in patients who are coinfected with HIV-1 and HBV.

Monitor Prior to starting or reintroducing therapy with abacavir, screening for the HLA-B∗5701 allele is recommended and may decrease the risk of hypersensitivity reactions. Patients who test negative for the allele may develop hypersensitivity reaction to abacavir; however, this occurs less frequently than in HLA-B∗5701–postive patients. Discontinuation Ensure hepatic function is closely monitored for at least several months following discontinuation of abacavir/lamivudine in patients who are coinfected with HBV and HIV. Ensure an anti-HBV therapy has been considered. Lactic acidosis Monitor patient for signs of lactic acidosis. If patient develops cold feeling, dizziness, light-headedness, profound weakness or tiredness, slow or irregular heartbeat, or unexpected stomach discomfort, withhold drug.

Pregnancy

Category C .

Lactation

HIV-infected mothers should not breast-feed their infants.

Abacavir

Undetermined.

Lamivudine

Excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Hypersensitivity

Do not administer to patient who has had a suspected or documented hypersensitivity reaction to abacavir. Abacavir has been associated with fatal hypersensitivity reactions and should not be restarted following a hypersensitivity reaction to abacavir.

Renal Function

Because this is a fixed-dose tablet, do not use for patients requiring dosage adjustment (CrCl less than 50 mL/min).

Hepatic Function

Because this is a fixed-dose tablet and the dosage of the individual components cannot be altered, it is contraindicated in patients with hepatic function impairment.

Antiretroviral agents

Must be used in combination with other antiretroviral agents from different pharmacologic classes (not with other nucleoside/nucleotide reverse transcriptase inhibitors).

Fat redistribution

Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement, peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance, have been observed in patients receiving antiretroviral therapy.

Fixed-dose combination

Abacavir/lamivudine contains fixed doses of 2 nucleoside analogs, abacavir and lamivudine, and should not be coadministered with other abacavir- and/or lamivudine-containing products.

HIV-1 and HBV coinfection

Not appropriate for the treatment of chronic HBV in patients dually infected with HIV-1 and HBV.

Immune reconstitution syndrome

Has been reported in patients receiving combination antiretroviral therapy, including abacavir/lamivudine. During the initial phase of treatment, patients may develop an inflammatory response to indolent or residual opportunistic infections (eg, Mycobacterium avium ), necessitating further evaluation and treatment.

MI

Use of abacavir within the 6 mo prior to combined antiretroviral therapy may increase the risk of MI.

Posttreatment exacerbations of hepatitis

In patients treated with lamivudine for chronic HBV, clinical and laboratory evidence of hepatitis exacerbations have occurred after discontinuation of lamivudine.

Therapy-experienced patients

Patients with prolonged prior nucleoside reverse transcriptase inhibitor (NRTI) exposure or who have HIV-1 isolates containing multiple mutations conferring NRTI resistance have limited response to abacavir. Thus, consider potential cross-resistance between abacavir and other NRTIs when selecting new regimens for therapy-experienced patients.

Patient Information

• Advise patient to review Medication Guide before starting therapy and with each refill of the medication.
• Advise patient to review, and carry at all times, the Warning Card summarizing the symptoms of abacavir hypersensitivity reaction.
• Instruct patient to take exactly as prescribed and not to change the dose or discontinue therapy unless advised by health care provider.
• Instruct patient to take 1 tablet once daily without regard to meals, but to take with food if stomach upset occurs.
• Warn patient that this drug is not to be used by itself but is combined with other antiviral agents and to continue to take other HIV medications as prescribed by health care provider.
• Instruct patient to discontinue use and notify health care provider immediately if a symptom from 2 or more of the following groups occurs: 1) fever; 2) rash; 3) nausea, vomiting, diarrhea, stomach pain; 4) generalized body discomfort, extreme tiredness, achiness; 5) sore throat, shortness of breath, cough.
• Caution patient not to restart this medication or any other abacavir-containing medication if a hypersensitivity reaction to this medication has occurred. Explain to patient that restarting abacavir or an abacavir-containing product could cause a more serious, and possibly fatal, reaction.
• Caution patient that if therapy is interrupted for a few days for reasons other than a hypersensitivity reaction (eg, interruption in drug supply) and is then restarted that there is a risk of experiencing a serious or fatal hypersensitivity reaction. Advise patient to talk with health care provider before restarting the medication. Advise patient that if health care provider tells them to take the medication again, to start taking it when they are around medical help or people who can call a doctor if necessary.
• Caution patient that medication can cause a rare but serious condition called lactic acidosis with liver enlargement and that persistent nausea and tiredness may be symptoms of this condition. Instruct patient to inform health care provider if these symptoms develop.
• Caution patient who has concurrent infection with HBV that hepatitis may worsen if abacavir/lamivudine is stopped and that liver function should be closely followed for several months after stopping abacavir/lamivudine. Advise patient that anti-HBV medications may be needed.
• Advise patient that medication may cause changes in body fat distribution (eg, increased amount of fat in upper back and neck, breasts, and around the back, chest, and stomach area; or loss of fat from arms, legs, and face) and that the cause and long-term health effects of these changes are not known at this time. Advise patient to report changes in body fat distribution to health care provider.
• Inform patient that drug does not completely eliminate HIV and, therefore, does not reduce the risk of transmitting HIV to others through sexual contact or blood contamination. Instruct patient that appropriate precautions must still be followed.
• Advise patient that drug is not a cure for HIV infection and that illnesses associated with HIV infection, including opportunistic infections, may continue to be acquired. Patients should remain under a health care provider's care.
• Instruct mother not to breast-feed her infant because of risk of transmitting HIV virus to the infant and the potential for serious adverse effects from medication transmitted to her infant through breast milk.

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