Abacavir and lamivudine

U.S. BRAND NAMES — Epzicom™
CANADIAN BRAND NAMES — Kivexa™
SYNONYMS — 3TC and ABC; 3TC and Abacavir; Abacavir and 3TC; ABC and 3TC; Lamivudine and Abacavir
THERAPEUTIC CATEGORY Antiretroviral AgentHIV Agents (Anti-HIV Agents)Nucleoside Analog Reverse Transcriptase Inhibitor (NRTI)
DOSING — Oral:
(For additional information see "Abacavir and lamivudine: Drug information")
Children and Adolescents <18 years of age: Not intended for pediatric use; product is a fixed-dose combination; safety and efficacy has not been established in pediatric patients
Adolescents 18 years of age and Adults: 1 tablet daily
Dosage adjustment in hepatic impairment: Use is contraindicated (use individual antiretroviral agents to reduce dosage)
Dosage adjustment in renal impairment: Clcr 50 mL/minute: Not recommended (use individual antiretroviral agents to reduce dosage)
DOSAGE FORMS — Abacavir component is available as abacavir sulfate; mg strength refers to abacavir
Tablet: Epzicom™: Abacavir 600 mg and lamivudine 300 mg
GENERIC AVAILABLE — No
ADMINISTRATION — May be administered without regards to meals.
USE — Treatment of HIV-1 infection (either alone or in combination with other antiretroviral agents) (Note: HIV regimens consisting of three antiretroviral agents are strongly recommended)
ADVERSE REACTIONS — See Abacavir and Lamivudine
CONTRAINDICATIONS — Hypersensitivity to abacavir, lamivudine, or any component; hepatic impairment. Do not rechallenge patients who have experienced hypersensitivity reactions to abacavir; potentially fatal hypersensitivity reactions may occur (see Warnings).
PRECAUTIONS — Fat redistribution and accumulation [ie, central obesity, peripheral wasting, facial wasting, breast enlargement, dorsocervical fat enlargement (buffalo hump), and cushingoid appearance] have been observed in patients receiving antiretroviral agents (causal relationship not established). Resistance to abacavir develops relatively slowly, but cross resistance between abacavir and other nucleoside reverse transcriptase inhibitors (NRTIs) may occur; limited response may be seen in patients with HIV isolates containing multiple mutations conferring resistance to NRTIs or in patients with a prolonged prior NRTI exposure.
Immune reconstitution syndrome (an acute inflammatory response to residual or indolent opportunistic infections) may occur in HIV patients during initial treatment with combination antiretroviral agents, including abacavir and lamivudine; this syndrome may require further patient assessment and therapy. Systemic exposure of abacavir at 6-32 times the normal human exposure, increased the incidence of tumors (malignant and nonmalignant) in mice and rats; myocardial degeneration was seen in mice and rats receiving abacavir for 2 years at 7-24 times the expected human exposure; the clinical relevance of these findings is currently unknown
WARNINGS — Serious and sometimes fatal hypersensitivity reactions to abacavir may occur; discontinue therapy immediately in patients who show signs or symptoms of 2 or more of the following: Fever, skin rash, respiratory symptoms (including cough, dyspnea, or pharyngitis), GI symptoms (including nausea, vomiting, diarrhea, or abdominal pain), and constitutional symptoms (including fatigue, malaise, or achiness). Carefully consider the diagnosis of hypersensitivity reaction in patients who present with acute onset respiratory symptoms, even if other diagnoses, such as bronchitis, flu-like illness, pharyngitis, or pneumonia, are possible. Permanently discontinue abacavir-containing medications if hypersensitivity reaction cannot be ruled out, even when other diagnoses are possible. Skin rash may be maculopapular or urticarial, but can be variable in appearance; erythema multiforme has been reported; hypersensitivity reaction may occur without a rash. Other symptoms may include edema, lethargy, myolysis, paresthesia, shortness of breath, mouth ulcerations, conjunctivitis, lymphadenopathy, and abnormal findings on chest x-ray (ie, infiltrates that can be localized). Anaphylaxis, renal failure, hepatic failure, respiratory failure, ARDS, hypotension, and death may also occur in association with hypersensitivity reactions. Laboratory abnormalities include increases in liver function tests, elevated CPK or serum creatinine, and lymphopenia.
Do not restart abacavir, Epzicom™, or any other abacavir-containing product after a hypersensitivity reaction occurs; more severe symptoms can recur within hours and may include life-threatening hypotension and death. Fatal hypersensitivity reactions have occurred following the reintroduction of abacavir in patients whose therapy was interrupted for other reasons. These patients had no identified history or had unrecognized symptoms of abacavir hypersensitivity. Reactions occurred within hours. In some cases, signs of a hypersensitivity reaction may have been previously present, but attributed to other medical conditions (acute onset respiratory diseases, gastroenteritis, or reactions to other medications). If abacavir, Epzicom™ or any other abacavir-containing product is to be restarted following an interruption in therapy, the patient must first be evaluated for previously unsuspected symptoms of hypersensitivity. Do not restart abacavir, Epzicom™, or any other abacavir-containing product if hypersensitivity is suspected or cannot be ruled out. Hypersensitivity reactions occur in ~8% of adult and pediatric patients; most hypersensitivity reactions occur within the first 6 weeks of therapy, but can occur at any time; call the Abacavir Hypersensitivity Reaction Registry at 1-800-270-0425 to facilitate reporting and collection of information on patients experiencing abacavir hypersensitivity reactions (see Additional Information).
Cases of lactic acidosis, severe hepatomegaly with steatosis, and death have been reported in patients receiving nucleoside analogues; most of these cases have been in women; prolonged nucleoside use, obesity, and prior liver disease may be risk factors; use with extreme caution in patients with other risk factors for liver disease; discontinue Epzicom™ in patients who develop laboratory or clinical evidence of lactic acidosis or pronounced hepatotoxicity.
The major clinical toxicity of lamivudine in pediatric patients is pancreatitis; discontinue therapy if clinical signs, symptoms, or laboratory abnormalities suggestive of pancreatitis occur. HIV-infected patients who are coinfected with hepatitis B may experience clinical symptoms or laboratory evidence of hepatitis when a lamivudine-containing medication is discontinued; most cases are self-limited, but fatalities have been reported; monitor patients closely for at least several months after discontinuation of abacavir and lamivudine. Concomitant use of combination antiretroviral therapy with interferon alfa (with or without ribavirin) has resulted in hepatic decompensation (with some fatalities) in patients coinfected with HIV and HCV; monitor patients closely, especially for hepatic decompensation; consider discontinuation of abacavir and lamivudine if needed; consider dose reduction or discontinuation of interferon alfa, ribavirin, or both if clinical toxicities, including hepatic decompensation, worsen.
Epzicom™ contains abacavir and lamivudine as a fixed-dose combination; do not use in patients with renal dysfunction (Clcr 50 mL/minute) who require lamivudine dosage adjustment or in patients with hepatic dysfunction (Note: Abacavir is contraindicated in patients with moderate to severe hepatic dysfunction; patients with mild hepatic impairment require abacavir dosage reduction). Do not administer Epzicom™ with abacavir, lamivudine, or emtricitabine-containing products.
DRUG INTERACTIONS — See Abacavir and Lamivudine
FOOD INTERACTIONS — Food decreases the rate, but not the extent of absorption; in a single dose study, a high-fat meal did not change bioavailability or peak concentrations.
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Signs and symptoms of abacavir hypersensitivity reaction, lactic acidosis, pronounced hepatotoxicity, and pancreatitis; serum glucose and triglycerides, viral load, CD4 counts, CBC with differential, hemoglobin, liver enzymes, serum amylase, bilirubin, renal and hepatic function tests; HIV patients should be screened for hepatitis B before starting lamivudine (see Warnings)
STABILITY — Store at room temperature 25ºC (77ºF).
MECHANISM OF ACTION — See Abacavir and Lamivudine
PHARMACOKINETICS — One Epzicom™ tablet is bioequivalent, in the extent (AUC) of absorption and peak concentration, to two abacavir 300 mg tablets and two lamivudine 150 mg tablets; see Abacavir and Lamivudine
PATIENT INFORMATION — Epzicom™ is not a cure for HIV. Take Epzicom™ every day as prescribed; do not change dose or discontinue without physician's advice. If Epzicom™ is stopped for any reason, notify physician before restarting therapy. If a dose is missed, take it as soon as possible, then return to normal dosing schedule; if a dose is skipped, do not double the next dose. Avoid alcohol. Notify physician if persistent severe abdominal pain, nausea, or vomiting occurs.
(For additional information see "Abacavir and lamivudine: Patient drug information")
Epzicom™ contains abacavir (also called Ziagen®). Abacavir may cause serious and sometimes fatal allergic (hypersensitivity) reactions. Read the Patient Medication Guide that you receive with each prescription and refill of abacavir and lamivudine. Stop taking Epzicom™ and notify physician immediately if 2 or more of the following sets of symptoms occur: Fever, rash, GI symptoms (nausea, vomiting, diarrhea, or abdominal pain); flu-like symptoms (severe tiredness, achiness, or generally ill feeling), or respiratory symptoms (sore throat, shortness of breath, cough). If you experience an allergic (hypersensitivity) reaction to Epzicom™ (or abacavir, Ziagen®, or Trizivir®), never take Epzicom™, abacavir, Ziagen®, or Trizivir® again.
HIV medications may cause changes in body fat, including an increase in fat in the upper back and neck, breasts, and trunk; a loss of fat from the face, arms, and legs may also occur. Some HIV medications (including abacavir and lamivudine) may cause a serious, but rare, condition called lactic acidosis with an increase in liver size (hepatomegaly). Before starting Epzicom™, inform your physician about your medical conditions, including any kidney or liver problems (including hepatitis B infection). Do not take Epzicom™ with Combivir®, Emtriva™, Epivir®, Epivir-HBV®, Trizivir®, Truvada®, or Ziagen®.
NURSING IMPLICATIONS — Inform patients of the possibility of a fatal abacavir hypersensitivity reaction and the signs and symptoms (see Warnings and Patient Information)
ADDITIONAL INFORMATION — The Patient Medication Guide, which includes written manufacturer information, should be dispensed to the patient with each new prescription and refill; a Warning Card describing the hypersensitivity reaction should be given to the patient to carry with them.
A high rate of early virologic failure in therapy-naive adult HIV patients has been observed with the once-daily three-drug combination therapy of abacavir, lamivudine, and tenofovir; this antiretroviral regimen is currently not recommended; any patient currently receiving this regimen should be closely monitored for virologic failure and considered for treatment modification