Abacavir and Lamivudine Tablets

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)].

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.

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 tablets, pediatric patients should be assessed for the ability to swallow tablets.

Not Recommended Due to Lack of Dosage Adjustment

Because Abacavir and Lamivudine Tablets is a fixed-dose tablet and cannot be dose adjusted, Abacavir and Lamivudine Tablets is not recommended for:

• patients with creatinine clearance less than 50 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.

Abacavir and Lamivudine Tablets USP
Abacavir and Lamivudine Tablets USP contain the following 2 synthetic nucleoside analogues: abacavir (ZIAGEN®, also a component of TRIZIVIR®) and lamivudine, USP (also known as EPIVIR® or 3TC) with inhibitory activity against HIV-1.

Abacavir and Lamivudine Tablets USP are for oral administration. Each yellow, 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 FD&C yellow #6, hypromellose, iron oxide yellow, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, sodium starch glycolate, and titanium dioxide.

Abacavir Sulfate, USP
The chemical name of abacavir sulfate, USP is (1S,cis)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol sulfate (salt) (2:1). Abacavir sulfate, USP is the enantiomer with 1S, 4R absolute configuration on the cyclopentene ring. It has the following structural formula:

(C14H18N6O)2•H2SO4 M.W. 670.76

Abacavir sulfate, USP is a white to off-white solid with a solubility of approximately 77 mg/mL in distilled water at 25°C.

In vivo, abacavir sulfate, USP dissociates to its free base, abacavir. Dosages are expressed in terms of abacavir.

Lamivudine, USP
The chemical name of lamivudine, USP is (2R,cis)-4-amino-1-(2-hydroxymethyl-1,3-oxathiolan-5-yl)-(1H)-pyrimidin-2-one. Lamivudine, USP is the (-)enantiomer of a dideoxy analogue of cytidine. Lamivudine, USP has also been referred to as (-)2′,3′-dideoxy, 3′-thiacytidine. It has the following structural formula:

C8H11N3O3S M.W. 229.3

Lamivudine, USP is a white to off-white crystalline solid with a solubility of approximately 70 mg/mL in water at 20°C.

Mechanism of Action

Abacavir and Lamivudine Tablets are an antiretroviral agent [see Microbiology (12.4)].

Pharmacokinetics

Pharmacokinetics in Adults

In a single-dose, 3-way crossover bioavailability trial of 1 Abacavir and Lamivudine Tablets versus 2 ZIAGEN® tablets (2 x 300 mg) and 2 EPIVIR® tablets (2 x 150 mg) administered simultaneously in healthy subjects (n = 25), there was no difference in the extent of absorption, as measured by the area under the plasma concentration-time curve (AUC) and maximal peak concentration (Cmax), of each component.

Abacavir: Following oral administration, abacavir is rapidly absorbed and extensively distributed. After oral administration of a single dose of 600 mg of abacavir in 20 subjects, Cmax was 4.26 ± 1.19 mcg per mL (mean ± SD) and AUC∞ was 11.95 ± 2.51 mcg•hour per mL. Binding of abacavir to human plasma proteins is approximately 50% and was independent of concentration. Total blood and plasma drug-related radioactivity concentrations are identical, demonstrating that abacavir readily distributes into erythrocytes. The primary routes of elimination of abacavir are metabolism by alcohol dehydrogenase to form the 5′-carboxylic acid and glucuronyl transferase to form the 5′-glucuronide.

Lamivudine: Following oral administration, lamivudine is rapidly absorbed and extensively distributed. After multiple-dose oral administration of lamivudine 300 mg once daily for 7 days to 60 healthy subjects, steady-state Cmax (Cmax,ss) was 2.04 ± 0.54 mcg per mL (mean ± SD) and the 24-hour steady-state AUC (AUC24,ss) was 8.87 ± 1.83 mcg•hour per mL. Binding to plasma protein is low. Approximately 70% of an intravenous dose of lamivudine is recovered as unchanged drug in the urine. Metabolism of lamivudine is a minor route of elimination. In humans, the only known metabolite is the trans-sulfoxide metabolite (approximately 5% of an oral dose after 12 hours).

In humans, abacavir and lamivudine are not significantly metabolized by cytochrome P450 enzymes.

The pharmacokinetic properties of abacavir and lamivudine in fasting subjects are summarized in Table 2.

Table 2. Pharmacokinetic Parameters* for Abacavir and Lamivudine in Adults

* Data presented as mean ± standard deviation except where noted. † Approximate range.
Parameter	Abacavir		Lamivudine
Oral bioavailability (%)	86 ± 25	n = 6	86 ± 16	n = 12
Apparent volume of distribution (L/kg)	0.86 ± 0.15	n = 6	1.3 ± 0.4	n = 20
Systemic clearance (L/h/kg)	0.80 ± 0.24	n = 6	0.33 ± 0.06	n = 20
Renal clearance (L/h/kg)	0.007 ± 0.008	n = 6	0.22 ± 0.06	n = 20
Elimination half-life (h)	1.45 ± 0.32	n = 20	5 to 7†

Effect of Food on Absorption of Abacavir and Lamivudine Tablets

Abacavir and Lamivudine Tablets may be administered with or without food. Administration with a high-fat meal in a single-dose bioavailability trial resulted in no change in AUClast, AUC∞, and Cmax for lamivudine. Food did not alter the extent of systemic exposure to abacavir (AUC∞), but the rate of absorption (Cmax) was decreased approximately 24% compared with fasted conditions (n = 25). These results are similar to those from previous trials of the effect of food on Abacavir and Lamivudine Tablets administered separately.

Specific Populations

Renal Impairment: Abacavir and Lamivudine Tablets: The effect of renal impairment on the combination of abacavir and lamivudine has not been evaluated (see the U.S. prescribing information for the individual abacavir and lamivudine components).

Hepatic Impairment: Abacavir and Lamivudine Tablets: The effect of hepatic impairment on the combination of abacavir and lamivudine has not been evaluated (see the U.S. prescribing information for the individual abacavir and lamivudine components).

Pregnancy: Abacavir: Abacavir pharmacokinetics were studied in 25 pregnant women during the last trimester of pregnancy receiving abacavir 300 mg twice daily. Abacavir exposure (AUC) during pregnancy was similar to those in postpartum and in HIV-infected non-pregnant historical controls. Consistent with passive diffusion of abacavir across the placenta, abacavir concentrations in neonatal plasma cord samples at birth were essentially equal to those in maternal plasma at delivery.

Lamivudine: Lamivudine pharmacokinetics were studied in 36 pregnant women during 2 clinical trials conducted in South Africa. Lamivudine pharmacokinetics in pregnant women were similar to those seen in non-pregnant adults and in postpartum women. Lamivudine concentrations were generally similar in maternal, neonatal, and umbilical cord serum samples.

Pediatric Patients: Abacavir and Lamivudine: The pharmacokinetic data for abacavir and lamivudine following administration of Abacavir and Lamivudine Tablets in pediatric subjects weighing 25 kg and above are limited. The dosing recommendations in this population are based on the safety and efficacy established in a controlled trial conducted using either the combination of EPIVIR® and ZIAGEN® or Abacavir and Lamivudine Tablets. Refer to the EPIVIR® and ZIAGEN® USPI for pharmacokinetic information on the individual products in pediatric patients [see Dosage and Administration (2.3), Adverse Reactions (6.1), Clinical Studies (14.2)].

Geriatric Patients: The pharmacokinetics of abacavir and lamivudine have not been studied in subjects over 65 years of age.

Gender: There are no significant or clinically relevant gender differences in the pharmacokinetics of the individual components (abacavir or lamivudine) based on the available information that was analyzed for each of the individual components.

Race: There are no significant or clinically relevant racial differences in pharmacokinetics of the individual components (abacavir or lamivudine) based on the available information that was analyzed for each of the individual components.

Drug Interactions

The drug interactions described are based on trials conducted with abacavir or lamivudine as single entities; no drug interaction trials have been conducted with Abacavir and Lamivudine Tablets.

Cytochrome P450 Enzymes: In humans, abacavir and lamivudine are not significantly metabolized by cytochrome P450 enzymes nor do they inhibit or induce this enzyme system; therefore, it is unlikely that clinically significant drug interactions will occur with drugs metabolized through these pathways.

Abacavir: Lamivudine and/or Zidovudine: Fifteen HIV-1-infected subjects were enrolled in a crossover-designed drug interaction trial evaluating single doses of abacavir (600 mg), lamivudine (150 mg), and zidovudine (300 mg) alone or in combination. Analysis showed no clinically relevant changes in the pharmacokinetics of abacavir with the addition of lamivudine or zidovudine or the combination of lamivudine and zidovudine. Lamivudine exposure (AUC decreased 15%) and zidovudine exposure (AUC increased 10%) did not show clinically relevant changes with concurrent abacavir.

Lamivudine: Zidovudine: No clinically significant alterations in lamivudine or zidovudine pharmacokinetics were observed in 12 asymptomatic HIV-1-infected adult subjects given a single dose of zidovudine (200 mg) in combination with multiple doses of lamivudine (300 mg every 12 h).

Other Interactions

Ethanol: Abacavir has no effect on the pharmacokinetic properties of ethanol. Ethanol decreases the elimination of abacavir causing an increase in overall exposure.

Methadone: In a trial of 11 HIV-1-infected subjects receiving methadone-maintenance therapy (40 mg and 90 mg daily), with 600 mg of ZIAGEN® twice daily (twice the currently recommended dose), oral methadone clearance increased 22% (90% CI: 6% to 42%) [see Drug Interactions (7)]. The addition of methadone has no clinically significant effect on the pharmacokinetic properties of abacavir.

Ribavirin: In vitro data indicate ribavirin reduces phosphorylation of lamivudine, stavudine, and zidovudine. However, no pharmacokinetic (e.g., plasma concentrations or intracellular triphosphorylated active metabolite concentrations) or pharmacodynamic (e.g., loss of HIV-1/HCV virologic suppression) interaction was observed when ribavirin and lamivudine (n = 18), stavudine (n = 10), or zidovudine (n = 6) were coadministered as part of a multi-drug regimen to HIV-1/HCV co-infected subjects [see Warnings and Precautions (5.4)].

Interferon Alfa: There was no significant pharmacokinetic interaction between lamivudine and interferon alfa in a trial of 19 healthy male subjects.

The effects of other coadministered drugs on abacavir or lamivudine are provided in Table 3.

Table 3. Effect of Coadministered Drugs on Abacavir or Lamivudine

* The drug-drug interaction was only evaluated in males.
Coadministered Drug and Dose	Drug and Dose	n	Concentrations of Abacavir or Lamivudine		Concentration of Coadministered Drug
			AUC	Variability
Ethanol 0.7 g/kg	Abacavir Single 600 mg	24	↑41%	90% CI: 35% to 48%	↔ *
Nelfinavir 750 mg every 8 h x 7 to 10 days	Lamivudine Single 150 mg	11	↑10%	95% CI: 1% to 20%	↔
Trimethoprim 160 mg/Sulfamethoxazole 800 mg daily x 5 days	Lamivudine Single 300 mg	14	↑43%	90% CI: 32% to 55%	↔
↑ = Increase; ↔ = No significant change; AUC = Area under the concentration versus time curve; CI = Confidence interval.

Microbiology

Mechanism of Action

Abacavir: Abacavir is a carbocyclic synthetic nucleoside analogue. Abacavir is converted by cellular enzymes to the active metabolite, carbovir triphosphate (CBV-TP), an analogue of deoxyguanosine-5′-triphosphate (dGTP). CBV-TP inhibits the activity of HIV-1 reverse transcriptase (RT) both by competing with the natural substrate dGTP and by its incorporation into viral DNA.

Lamivudine: Lamivudine is a synthetic nucleoside analogue. 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 RT via DNA chain termination after incorporation of the nucleotide analogue.

Antiviral Activity

Abacavir: The antiviral activity of abacavir against HIV-1 was assessed in a number of cell lines including primary monocytes/macrophages and peripheral blood mononuclear cells (PBMCs). EC50 values ranged from 3.7 to 5.8 microM (1 microM = 0.28 mcg per mL) and 0.07 to 1.0 microM against HIV-1IIIB and HIV-1BaL, respectively, and the mean EC50 value was 0.26 ± 0.18 microM against 8 clinical isolates. The median EC50 values of abacavir were 344 nM (range: 14.8 to 676 nM), 16.9 nM (range: 5.9 to 27.9 nM), 8.1 nM (range: 1.5 to 16.7 nM), 356 nM (range: 35.7 to 396 nM), 105 nM (range: 28.1 to 168 nM), 47.6 nM (range: 5.2 to 200 nM), 51.4 nM (range: 7.1 to 177 nM), and 282 nM (range: 22.4 to 598 nM) against HIV-1 clades A-G and group O viruses (n = 3 except n = 2 for clade B), respectively. The EC50 values against HIV-2 isolates (n = 4) ranged from 0.024 to 0.49 microM.

Lamivudine: The antiviral activity of lamivudine against HIV-1 was assessed in a number of cell lines including monocytes and PBMCs using standard susceptibility assays. EC50 values were in the range of 0.003 to 15 microM (1 microM = 0.23 mcg per mL). The median EC50 values of lamivudine were 60 nM (range: 20 to 70 nM), 35 nM (range: 30 to 40 nM), 30 nM (range: 20 to 90 nM), 20 nM (range: 3 to 40 nM), 30 nM (range: 1 to 60 nM), 30 nM (range: 20 to 70 nM), 30 nM (range: 3 to 70 nM), and 30 nM (range: 20 to 90 nM) against HIV-1 clades A-G and group O viruses (n = 3 except n = 2 for clade B), respectively. The EC50 values against HIV-2 isolates (n = 4) ranged from 0.003 to 0.120 microM in PBMCs. Ribavirin (50 microM) used in the treatment of chronic HCV infection decreased the anti-HIV-1 activity of lamivudine by 3.5-fold in MT-4 cells.

The combination of abacavir and lamivudine has demonstrated antiviral activity in cell culture against non-subtype B isolates and HIV-2 isolates with equivalent antiviral activity as for subtype B isolates. Neither abacavir, nor lamivudine, were antagonistic to all tested anti-HIV agents. See full prescribing information for ZIAGEN® (abacavir) and EPIVIR® (lamivudine). Ribavirin, used in the treatment of HCV infection, decreased the anti-HIV-1 potency of abacavir/lamivudine reproducibly by 2- to 6-fold in cell culture.

Resistance

HIV-1 isolates with reduced susceptibility to the combination of abacavir and lamivudine have been selected in cell culture with amino acid substitutions K65R, L74V, Y115F, and M184V/I emerging in HIV-1 RT. M184V or I substitutions resulted in high-level resistance to lamivudine and an approximately 2-fold decrease in susceptibility to abacavir. Substitutions K65R, L74M, or Y115F with M184V or I conferred a 7- to 8-fold reduction in abacavir susceptibility, and combinations of three substitutions were required to confer more than an 8-fold reduction in susceptibility.

Cross-Resistance

Cross-resistance has been observed among nucleoside reverse transcriptase inhibitors (NRTIs). The combination of abacavir/lamivudine has demonstrated decreased susceptibility to viruses with a K65R substitution with or without an M184V/I substitution, viruses with L74V plus the M184V/I substitution, and viruses with thymidine analog mutation substitutions (TAMs: M41L, D67N, K70R, L210W, T215Y/F, K219E/R/H/Q/N) plus M184V. An increasing number of TAMs is associated with a progressive reduction in abacavir susceptibility.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Hypersensitivity Reactions
Inform patients:

• that a Medication Guide and Warning Card summarizing the symptoms of the abacavir hypersensitivity reaction and other product information will be dispensed by the pharmacist with each new prescription and refill of Abacavir and Lamivudine Tablets, and instruct the patient to read the Medication Guide and Warning Card every time to obtain any new information that may be present about Abacavir and Lamivudine Tablets. The complete text of the Medication Guide is reprinted at the end of this document. • to carry the Warning Card with them. • how to identify a hypersensitivity reaction [see Warnings and Precautions (5.1), Medication Guide]. • that if they develop symptoms consistent with a hypersensitivity reaction they should call their healthcare provider right away to determine if they should stop taking Abacavir and Lamivudine Tablets. • that a hypersensitivity reaction can worsen and lead to hospitalization or death if Abacavir and Lamivudine Tablets are not immediately discontinued. • to not restart Abacavir and Lamivudine Tablets or any other abacavir-containing product following a hypersensitivity reaction because more severe symptoms can occur within hours and may include life-threatening hypotension and death. • that if they have a hypersensitivity reaction, they should dispose of any unused Abacavir and Lamivudine Tablets to avoid restarting abacavir. • that a hypersensitivity reaction is usually reversible if it is detected promptly and Abacavir and Lamivudine Tablets are stopped right away. • that if they have interrupted Abacavir and Lamivudine Tablets for reasons other than symptoms of hypersensitivity (for example, those who have an interruption in drug supply), a serious or fatal hypersensitivity reaction may occur with reintroduction of abacavir. • to not restart Abacavir and Lamivudine Tablets or any other abacavir-containing product without medical consultation and only if medical care can be readily accessed by the patient or others.

Lactic Acidosis/Hepatomegaly with Steatosis
Advise patients that lactic acidosis and severe hepatomegaly with steatosis have been reported with use of nucleoside analogues and other antiretrovirals. Advise patients to stop taking Abacavir and Lamivudine Tablets if they develop clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity [see Warnings and Precautions (5.2)].

Patients with Hepatitis B or C Co-infection
Advise patients co-infected with HIV-1 and HBV that worsening of liver disease has occurred in some cases when treatment with lamivudine was discontinued. Advise patients to discuss any changes in regimen with their physician [see Warnings and Precautions (5.3)].

Inform patients with HIV-1/HCV co-infection that hepatic decompensation (some fatal) has occurred in HIV-1/HCV co-infected patients receiving combination antiretroviral therapy for HIV-1 and interferon alfa with or without ribavirin [see Warnings and Precautions (5.4)].

Immune Reconstitution Syndrome

Advise patients to inform their healthcare provider immediately of any signs and symptoms of infection as inflammation from previous infection may occur soon after combination antiretroviral therapy, including when Abacavir and Lamivudine Tablets are started [see Warnings and Precautions (5.5)].

Redistribution/Accumulation of Body Fat

Inform patients that redistribution or accumulation of body fat may occur in patients receiving antiretroviral therapy and that the cause and long-term health effects of these conditions are not known at this time [see Warnings and Precautions (5.6)].

Pregnancy Registry

Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Abacavir and Lamivudine Tablets during pregnancy [see Use in Specific Populations (8.1)].

Lactation

Instruct women with HIV-1 infection not to breastfeed because HIV-1 can be passed to the baby in the breast milk [see Use in Specific Populations (8.2)].

Missed Dose

Instruct patients that if they miss a dose of Abacavir and Lamivudine Tablets, to take it as soon as they remember. Advise patients not to double their next dose or take more than the prescribed dose [see Dosage and Administration (2)].

Availability of Medication Guide

Instruct patients to read the Medication Guide before starting Abacavir and Lamivudine Tablets and to re-read it each time the prescription is renewed. Instruct patients to inform their physician or pharmacist if they develop any unusual symptom, or if any known symptom persists or worsens.

All brand names listed are the registered trademarks of their respective owners and are not trademarks of Teva Pharmaceuticals USA, Inc.

Teva Pharmaceuticals USA, Inc.

North Wales, PA 19454

Rev. A 3/2017

Abacavir (a-BAK-a-vir) and Lamivudine (la-MIV-ue-deen) Tablets USP

What is the most important information I should know about Abacavir and Lamivudine Tablets?

Abacavir and Lamivudine Tablets can cause serious side effects, including:

• Serious allergic reactions (hypersensitivity reaction) that can cause death have happened with Abacavir and Lamivudine Tablets and other abacavir-containing products. Your risk of this allergic reaction is much higher if you have a gene variation called HLA-B*5701. Your healthcare provider can determine with a blood test if you have this gene variation.

If you get a symptom from 2 or more of the following groups while taking Abacavir and Lamivudine Tablets, call your healthcare provider right away to find out if you should stop taking Abacavir and Lamivudine Tablets.

	Symptom(s)
Group 1	Fever
Group 2	Rash
Group 3	Nausea, vomiting, diarrhea, abdominal (stomach area) pain
Group 4	Generally ill feeling, extreme tiredness, or achiness
Group 5	Shortness of breath, cough, sore throat

A list of these symptoms is on the Warning Card your pharmacist gives you. Carry this Warning Card with you at all times.

If you stop Abacavir and Lamivudine Tablets because of an allergic reaction, never take Abacavir and Lamivudine Tablets or any other abacavir-containing medicine (TRIUMEQ®, TRIZIVIR® or ZIAGEN®) again.

• If you have an allergic reaction, dispose of any unused Abacavir and Lamivudine Tablets. Ask your pharmacist how to properly dispose of medicines. • If you take Abacavir and Lamivudine Tablets or any other abacavir-containing medicine again after you have had an allergic reaction, within hours you may get life-threatening symptoms that may include very low blood pressure ordeath. • If you stop Abacavir and Lamivudine Tablets for any other reason, even for a few days, and you are not allergic to Abacavir and Lamivudine Tablets, talk with your healthcare provider before taking them again. Taking Abacavir and Lamivudine Tablets again can cause a serious allergic or life-threatening reaction, even if you never had an allergic reaction to them before.

If your healthcare provider tells you that you can take Abacavir and Lamivudine Tablets again, start taking them when you are around medical help or people who can call a healthcare provider if you need one.

• Build up of acid in your blood (lactic acidosis). Lactic acidosis can happen in some people who take Abacavir and Lamivudine Tablets. Lactic acidosis is a serious medical emergency that can cause death. Call your healthcare provider right away if you get any of the following symptoms that could be signs of lactic acidosis:
• feel very weak or tired • unusual (not normal) muscle pain • trouble breathing • stomach pain with nausea and vomiting • feel cold, especially in your arms and legs • feel dizzy or light-headed • have a fast or irregular heartbeat
• Serious liver problems can happen in people who take Abacavir and Lamivudine Tablets. In some cases, these serious liver problems can lead to death. Your liver may become large (hepatomegaly) and you may develop fat in your liver (steatosis). Call your healthcare provider right away if you get any of the following signs or symptoms of liver problems: • your skin or the white part of your eyes turns yellow (jaundice) • dark or “tea-colored” urine • light-colored stools (bowel movements) • loss of appetite for several days or longer • nausea • pain, aching, or tenderness on the right side of your stomach area

You may be more likely to get lactic acidosis or serious liver problems if you are female, very overweight (obese), or have been taking nucleoside analogue medicines for a long time.

• Worsening of hepatitis B virus in people who have HIV-1 infection. If you have HIV-1 and hepatitis B virus (HBV) infection, your HBV may get worse (flare-up) if you stop taking Abacavir and Lamivudine Tablets. A “flare-up” is when your HBV infection suddenly returns in a worse way than before. Worsening liver disease can be serious and may lead to death. • Do not run out of Abacavir and Lamivudine Tablets. Refill your prescription or talk to your healthcare provider before your Abacavir and Lamivudine Tablets are all gone. • Do not stop Abacavir and Lamivudine Tablets without first talking to your healthcare provider. • If you stop taking Abacavir and Lamivudine Tablets, your healthcare provider will need to check your health often and do blood tests regularly for several months to check your liver. • Resistant Hepatitis B Virus (HBV). If you have HIV-1 and hepatitis B, the hepatitis B virus can change (mutate) during your treatment with Abacavir and Lamivudine Tablets and become harder to treat (resistant). • Use with interferon and ribavirin-based regimens. Worsening of liver disease that has caused death has happened in people infected with both HIV-1 and hepatitis C virus who are taking antiretroviral medicines and are also being treated for hepatitis C with interferon with or without ribavirin. If you are taking Abacavir and Lamivudine Tablets and interferon with or without ribavirin tell your healthcare provider if you have any new symptoms.

What are Abacavir and Lamivudine Tablets?

Abacavir and Lamivudine Tablets are a prescription HIV-1 (Human Immunodeficiency Virus-type 1) medicine used with other antiretroviral medicines to treat HIV-1 infection. HIV-1 is the virus that causes Acquired Immune Deficiency Syndrome (AIDS). Abacavir and Lamivudine Tablets contain 2 prescription medicines, abacavir (ZIAGEN®) and lamivudine (EPIVIR®).

Abacavir and Lamivudine Tablets should not be used in children weighing less than 55 pounds (25 kg).

When used with other antiretroviral medicines to treat HIV-1 infection, Abacavir and Lamivudine Tablets may help:

• reduce the amount of HIV-1 in your blood. This is called “viral load”. • increase the number of CD4+ (T) cells in your blood, that help fight off other infections.

Reducing the amount of HIV-1 and increasing the CD4+ (T) cells in your blood may help improve your immune system. This may reduce your risk of death or getting infections that can happen when your immune system is weak (opportunistic infections).

Abacavir and Lamivudine Tablets do not cure HIV-1 infection or AIDS. You must keep taking HIV-1 medicines to control HIV-1 infection and decrease HIV-related illnesses.

Who should not take Abacavir and Lamivudine Tablets?

Do not take Abacavir and Lamivudine Tablets if you:

• have a certain type of gene variation called the HLA-B*5701 allele. Your healthcare provider will test you for this before prescribing treatment with Abacavir and Lamivudine Tablets. • are allergic to abacavir or any of the ingredients in Abacavir and Lamivudine Tablets. See the end of this Medication Guide for a complete list of ingredients in Abacavir and Lamivudine Tablets. • have liver problems.

What should I tell my healthcare provider before taking Abacavir and Lamivudine Tablets?

Before you take Abacavir and Lamivudine Tablets tell your healthcare provider if you:

• have been tested and know whether or not you have a particular gene variation called HLA-B*5701. • have or have had liver problems, including hepatitis B or C virus infection. • have kidney problems. • have heart problems, smoke, or have diseases that increase your risk of heart disease such as high blood pressure, high cholesterol, or diabetes. • drink alcohol or take medicines that contain alcohol. • are pregnant or plan to become pregnant. Talk to your healthcare provider if you are pregnant or plan to become pregnant.
Pregnancy Registry. There is a pregnancy registry for women who take antiretroviral medicines during pregnancy. The purpose of this registry is to collect information about the health of you and your baby. Talk to your healthcare provider about how you can take part in this registry. • are breastfeeding or plan to breastfeed. Do not breastfeed if you take Abacavir and Lamivudine Tablets. • You should not breastfeed if you have HIV-1 because of the risk of passing HIV-1 to your baby.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Some medicines interact with Abacavir and Lamivudine Tablets. Keep a list of your medicines to show your healthcare provider and pharmacist. You can ask your healthcare provider or pharmacist for a list of medicines that interact with Abacavir and Lamivudine Tablets. Do not start taking a new medicine without telling your healthcare provider. Your healthcare provider can tell you if it is safe to take Abacavir and Lamivudine Tablets with other medicines.

Tell your healthcare provider if you take:

• any other medicine to treat HIV-1 • medicines to treat hepatitis viruses such as interferon or ribavirin • methadone

How should I take Abacavir and Lamivudine Tablets?

• Take Abacavir and Lamivudine Tablets exactly as your healthcare provider tells you. • Do not change your dose or stop taking Abacavir and Lamivudine Tablets without talking with your healthcare provider. If you miss a dose of Abacavir and Lamivudine Tablets, take it as soon as you remember. Do not take 2 doses at the same time. If you are not sure about your dosing, call your healthcare provider. • Stay under the care of a healthcare provider while taking Abacavir and Lamivudine Tablets. • Abacavir and Lamivudine Tablets may be taken with or without food. • Tell your healthcare provider if your child has trouble swallowing Abacavir and Lamivudine Tablets. • Do not run out of Abacavir and Lamivudine Tablets. The virus in your blood may increase and the virus may become harder to treat. When your supply starts to run low, get more from your healthcare provider or pharmacy. • If you take too many Abacavir and Lamivudine Tablets, call your healthcare provider or go to the nearest hospital emergency room right away.

What are the possible side effects of Abacavir and Lamivudine Tablets?

• Abacavir and Lamivudine Tablets can cause serious side effects including: • See “What is the most important information I should know about Abacavir and Lamivudine Tablets?” • Changes in your immune system (Immune Reconstitution Syndrome) can happen when you start taking HIV-1 medicines. Your immune system may get stronger and begin to fight infections that have been hidden in your body for a long time. Tell your healthcare provider right away if you start having new symptoms after you start taking Abacavir and Lamivudine Tablets. • Changes in body fat can happen in people who take HIV-1 medicines. These changes may include an increased amount of fat in the upper back and neck (“buffalo hump”), breast, and around the middle of your body (trunk). Loss of fat from the legs, arms, and face may also happen. The exact cause and long-term health effects of these conditions are not known. • Heart attack (myocardial infarction). Some HIV-1 medicines including Abacavir and Lamivudine Tablets may increase your risk of heart attack.

The most common side effects of Abacavir and Lamivudine Tablets include:

• trouble sleeping • depression • headache • tiredness • dizziness • nausea • diarrhea • rash • fever

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Abacavir and Lamivudine Tablets. For more information, ask your healthcare provider or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Abacavir and Lamivudine Tablets?

• Store Abacavir and Lamivudine Tablets between 68° to 77°F (20° to 25°C).

Keep Abacavir and Lamivudine Tablets and all medicines out of the reach of children.

General information for safe and effective use of Abacavir and Lamivudine Tablets.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Abacavir and Lamivudine Tablets for a condition for which they were not prescribed. Do not give Abacavir and Lamivudine Tablets to other people, even if they have the same symptoms that you have. They may harm them.

If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for the information about Abacavir and Lamivudine Tablets that is written for health professionals.

For more information call 1-888-838-2872.

What are the ingredients in Abacavir and Lamivudine Tablets USP?

Active ingredients: abacavir sulfate, USP and lamivudine, USP

Inactive ingredients: FD&C yellow #6, hypromellose, iron oxide yellow, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, sodium starch glycolate, and titanium dioxide.

All brand names listed are the registered trademarks of their respective owners and are not trademarks of Teva Pharmaceuticals USA, Inc.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Teva Pharmaceuticals USA, Inc.

North Wales, PA 19454

Rev. A 3/2017

Abacavir and Lamivudine Tablets USP 600 mg/300 mg, 30s Bottle, Carton Text

NDC 0093-5382-56

Abacavir and

Lamivudine Tablets USP

600 mg/300 mg

Each film-coated tablet contains 600 mg of abacavir as

abacavir sulfate, USP and 300 mg lamivudine, USP.

Notice to Authorized Dispenser: Each time abacavir and

lamivudine tablets USP are dispensed, give the patient a

Medication Guide and Warning Card from the carton.

Rx only

30 TABLETS

TEVA

ABACAVIR AND LAMIVUDINE  abacavir and lamivudine tablet, film coated

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0093-5382 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ABACAVIR SULFATE (ABACAVIR) ABACAVIR 600 mg LAMIVUDINE (LAMIVUDINE) LAMIVUDINE 300 mg

Inactive Ingredients Ingredient Name Strength FD&C YELLOW NO. 6   HYPROMELLOSE 2910 (6 MPA.S)   FERRIC OXIDE YELLOW   MAGNESIUM STEARATE   MICROCRYSTALLINE CELLULOSE   POLYETHYLENE GLYCOL 400   POLYSORBATE 80   SODIUM STARCH GLYCOLATE TYPE A POTATO   TITANIUM DIOXIDE

Product Characteristics Color YELLOW Score no score Shape OVAL (capsule-shaped) Size 19mm Flavor Imprint Code 5382;TV Contains

Packaging # Item Code Package Description 1 NDC:0093-5382-56 1 BOTTLE in 1 CARTON 1 30 TABLET, FILM COATED in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA079246 09/29/2016

Labeler - Teva Pharmaceuticals USA, Inc. (001627975)

Revised: 04/2017   Teva Pharmaceuticals USA, Inc.