Abacavir sulfate, lamivudine.
Each tablet contains abacavir 600 mg (as abacavir sulfate) and lamivudine 300 mg.
Excipients/Inactive Ingredients: Microcrystalline cellulose, croscarmellose sodium, povidone K30, crospovidone, talcum, magnesium stearate, and Opadry orange YS-1-13065-A*.
*Opadry orange YS-1-13065-A contains Hydroxypropyl Methylcellulose (HPMC), Titanium Dioxide, Polyethylene Glycol (PEG) 400, FD&C Yellow #6/Sunset Yellow FCF Aluminum lake, and Polysorbate 80.
Pharmacology: Pharmacodynamics: Mechanism of action: Abacavir: Abacavir is a carbocyclic synthetic nucleoside analog. Abacavir is converted by cellular enzymes to the active metabolite, carbovir triphosphate (CBV-TP), an analog of deoxyguanosine-5'-triphosphate (dGTP). CBV-TP inhibits the activity of HIV-1 reverse transcriptase by competing with the native substrate dGTP and by its incorporation into viral DNA. The lack of a 3'-OH group in the incorporated nucleotide analogue prevents the formation of the 5' to 3' phosphodiester linkage essential for DNA chain elongation, and therefore, the viral DNA growth is terminated. CBV-TP is a weak inhibitor of cellular DNA polymerases alpha, beta, and gamma.
Lamivudine: Lamivudine is a synthetic nucleoside analog. Intracellularly, lamivudine is phosphorylated to its active 5'-triphosphate metabolite, lamivudine triphosphate (3TC-TP). The principal mode of action of 3TC-TP is inhibition of reverse transcriptase via DNA chain termination after incorporation of the nucleotide analogue. 3TC-TP are weak inhibitors of cellular DNA polymerases alpha, beta, and gamma.
Dose/concentration/time-pharmacodynamic response relationship: Data is not available.
Pharmacokinetics: Absorption: Abacavir: Following oral administration, abacavir is rapidly absorbed and extensively distributed. After oral administration of a single dose of abacavir 600 mg, peak plasma concentration (Cmax) was 4.26±1.19 mcg/mL and area under the curve (AUC) was 11.95±2.51 mcg·h/mL. The oral bioavailability of abacavir is 86±25%.
Lamivudine: Following oral administration, lamivudine is rapidly absorbed and extensively distributed. After multiple-dose oral administration of lamivudine 300 mg one daily for 7 days, steady-state Cmax (Cmax,ss) was 2.04±0.54 mcg/mL and the 24-hour steady-state AUC (AUC24,ss) was 8.87±1.83 mcg·h/mL. The oral bioavailability of lamivudine is 86±16%.
Distribution: Abacavir: The apparent volume of distribution of abacavir is 0.86±0.15 L/kg. Binding of abacavir to human plasma proteins is approximately 50% and was independent of concentration. Abacavir readily distributes into erythrocytes.
Lamivudine: The apparent volume of distribution of lamivudine is 1.3±0.4 L/kg. Binding to plasma protein is low.
Metabolism: Abacavir: The primary routes of abacavir are metabolism by alcohol dehydrogenase to form the 5'-carboxylic acid and glucuronyl transferase to form the 5'-glucuronide.
Lamivudine: Metabolism of lamivudine is a minor route of elimination. The only known metabolite is the trans-sulfoxide metabolite (approximately 5% of an oral dose after 12 hours).
Elimination: Abacavir: The systemic and renal clearances of abacavir are 0.8±0.24 and 0.007±0.008 L/h/kg, respectively. Its elimination half-life is 1.45±0.32 hours.
Lamivudine: The systemic and renal clearances of lamivudine are 0.33±0.06 and 0.22±0.06 L/h/kg, respectively. Its elimination half-life approximately ranges from 5 to 7 hours. Approximately 70% of an intravenous dose of lamivudine is recovered as unchanged drug in the urine.
Special populations: Renal function impairment: Lamivudine requires dose adjustment in the presence of renal insufficiency; Alacovir tablet is not recommended for use in patients with CrCl less than 50 mL/min.
Hepatic function impairment: Abacavir is contraindicated in patients with moderate to severe hepatic impairment and dose reduction is required in patients with mild hepatic impairment. Because Alacovir tablet is a fixed-dose combination and cannot be dose adjusted, Alacovir tablet is contraindicated for patients with hepatic impairment.
Toxicology: Mechanism of toxicity: Data is not available.
Alacovir tablet is indicated for use in combination with other antiretroviral agents for the treatment of HIV-1 infection.
Recommended dose: Adults: 1 tablet daily, in combination with other antiretroviral agents.
Renal function impairment: Alacovir tablet is not recommended for use in patients with CrCl less than 50 mL/min.
Hepatic function impairment: Alacovir tablet is contraindicated in patients with hepatic impairment.
Mode of administration: Alacovir tablet may be taken with or without food.
Manifestation: No specific symptoms or signs have been identified following acute overdose with abacavir or lamivudine, apart from those listed as Adverse Reactions.
Treatment: If overdose occurs the patient should be monitored for evidence of toxicity and standard supportive treatment applied as necessary. Since lamivudine is dialysable, continuous hemodialysis could be used in the treatment of overdose, although this has not been studied. It is not known whether abacavir can be removed by peritoneal dialysis or hemodialysis.
Alacovir tablet is contraindicated to patients with hepatic impairment or hypersensitivity to abacavir, lamivudine or any component of the product.
Serious and sometimes fatal hypersensitivity reactions have been associated with abacavir. Hypersensitivity to abacavir is a multiorgan clinical syndrome usually characterized by a sign or symptom in 2 or more of the following groups: fever, rash, GI (eg, nausea, vomiting, diarrhea, abdominal pain), constitutional (eg, generalized malaise, fatigue, achiness), and respiratory (eg, dyspnea, cough, pharyngitis). Discontinue Alacovir tablet as soon as a hypersensitivity reaction is suspected.
Permanently discontinue Alacovir tablet if hypersensitivity cannot be ruled out, even when other diagnoses are possible.
Following a hypersensitivity reaction to abacavir, never restart Alacovir tablet or any other abacavir-containing product because more severe symptoms can occur within hours and may include life-threatening hypotension and death.
Reintroduction of Alacovir tablet or any other abacavir-containing product, even in patients who have no identified history of unrecognized symptoms of hypersensitivity to abacavir therapy, can result in serious or fatal hypersensitivity reactions. These reactions can occur within hours.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination, including abacavir, lamivudine, and other antiretrovirals.
Severe, acute exacerbation of hepatitis B have been reported in patients who are coinfected with hepatitis B virus (HBV) and HIV-1 and have discontinued lamivudine which is one component of Alacovir tablet. Closely monitor hepatic function with clinical and laboratory follow-up for at least several months in patients who discontinue Alacovir tablet and are coinfected with HIV-1 and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
Lactic acidosis and severe hepatomegaly with steatosis: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with use of nucleoside analogs alone or in combination, including abacavir, lamivudine and other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Exercise particular caution when administering Alacovir tablet to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Suspend treatment with Alacovir tablet in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatoxicity (which may include hepatomegaly and steatosis, even in the absence of marked transaminase elevations).
Immune Reconstitution Syndrome: Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including abacavir/lamivudine. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia (PJP), or tuberculosis), which may necessitate further evaluation and treatment.
Fat redistribution: Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy.
Emergence of lamivudine-resistant HBV: Safety and efficacy of lamivudine have not been established for treatment of chronic hepatitis B in patient dually infected with HIV-1 and HBV. In non-HIV-1-infected patients treated with lamivudine for chronic hepatits B; emergence of lamivudine-resistant HBV has been detected and has been associated with diminished treatment response. Emergence of hepatitis B virus variants associated with resistance to lamivudine has also been reported in HIV-1-infected patients who have received lamivudine-containing antiretroviral regimens in the presence of concurrent infection with hepatitis B virus.
Myocardial infarction: Consider the underlying risk of coronary heart disease when prescribing antiretroviral therapies, including abacavir, and take action to minimize all modifiable risk factors (eg, hypertension, hyperlipidemia, diabetes mellitus, smoking).
Renal function impairment: Because Alacovir is a fixed-dose tablet and the dosage of the individual components cannot be altered, patients with CrCl less than 50 mL/min should not receive Alacovir tablet.
Hepatic function impairment: Abacavir/lamivudine is contraindicated in patients with hepatic impairment because it is a fixed-dose tablet and the dosage of the individual components cannot be adjusted.
Effect on ability to drive and use machine: Data is not available.
Use in Children: Safety and effectiveness of abacavir/lamivudine in pediatric patients have not been established. Abacavir/lamivudine is not recommended for use in patients younger than 18 years because it cannot be dose adjusted.
Pregnancy: US Pregnancy category: C.
There are no adequate and well-controlled studies of abacavir/lamivudine in pregnant women. Use abacavir/lamivudine during pregnancy only if the potential benefits outweigh the risks. The updated guidelines for the use of antiretroviral agents in HIV-1-infected patients recommended that therapy, with the exception of efavirenz, should be continued during pregnancy.
Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.
Labor and delivery: Data is not available.
Lactation: The Centers for Disease Control and Prevention recommends that HIV-1-infected mothers not breast-feed their infants to avoid risking postnatal transmission of HIV-1. Abacavir is secreted in the milk of lactating rats. The molecular weight (about 671) suggests that abacavir may be excreted in human breast milk. Lamivudine is excreted in human breast milk and into the milk of lactating rats. Because of the potential for HIV-1 transmission and the potential for serious adverse reactions in breast-fed infants, instruct mothers not to breast-feed if they are receiving abacavir/lamivudine.
Common adverse reactions: Central nervous system:
Abnormal dreams, anxiety, depression/depressed mood, dizziness/vertigo, fatigue/malaise, headache/migraine, insomnia.
Abdominal pain/gastritis, diarrhea, nausea.
Drug hypersensitivity, pyrexia, rash.
Ethanol: Ethanol decreases the elimination of abacavir, causing an increase in overall exposure. Dosage adjustments are not needed.
Interferon alfa: Hepatic decompensation (some fatal) has occurred in HIV/Hepatitis C virus (HCV) coinfected patients receiving antiretroviral therapy for HIV-1 and interferon alfa, with or without ribavirin. Closely monitor patients for treatment-associated toxicities during coadministration.
Methadone: Methadone clearance increased 22% during coadministration. In the majority of patients, this alteration will not result in a methadone dose modification. In addition, methadone may delay the absorption of abacavir/lamivudine, resulting in a decrease in bioavailability.
Nelfinavir: Single-dose administration lamivudine 150 mg after pretreatment with nelfinavir 750 mg every 8 hours for 7-10 days increased the lamivudine AUC 10%. Dosage adjustments are not needed.
Ribavirin: Ribavirin may reduce the phosphorylation of lamivudine.
Trimethoprim/Sulfamethoxazole: Coadministration of lamivudine with trimethoprim 160 mg/sulfamethoxazole 800 mg increased lamivudine AUC 43%. Dosage adjustments are not needed.
Do not store above 30°C. Store in the original container.
J05AR02 - lamivudine and abacavir ; Belongs to the class of antivirals for treatment of HIV infections, combinations.
Tab (oblong, biconvex, orange film coated, one side debossed with "AL" and the other side is plain) 3 x 10's.