Lamivudine

Included as part of the PRECAUTIONS section.

• Hepatitis (Viral Hepatitis, A, B, C, D, E, G)
• Hepatitis B (HBV, Hep B)
• HIV and AIDS: Antiretroviral Drugs, Treatments and Medications

Lamivudine is part of the drug class:

• Nucleoside and nucleotide reverse transcriptase inhibitors

Serious side effects can occur with lamivudine use. See "Lamivudine Precautions" section.

Commonly reported side effects include:

• headache
• ear, nose or throat infections
• sore throat
• malaise (general ill feeling) and fatigue
• nausea
• diarrhea
• cough
• fever
• chills
• muscle and joint pain

This is not a complete list of lamivudine side effects. Ask your doctor or pharmacist for more information.

Before receiving lamivudine, tell your doctor if you:

• are allergic to lamivudine or any of the other ingredients of lamivudine
• have ever had liver disease such as liver failure, cirrhosis, or hepatitis
• are seriously overweight (especially if you’re a woman)
• are diabetic (Epivir HBV contains sucrose)
• use insulin
• have kidney disease
• have had pancreatitis (inflammation of the pancreas) in the past, particularly children

Tell your doctor if you are pregnant or breastfeeding.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

This medication falls into category C. It is not known if lamivudine will harm your unborn baby. There are no adequate and well-controlled trials of lamivudine in pregnant women.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended. You should not take Epivir (for treating HIV) together with Epivir-HBV (for treating hepatitis B).

Lamivudine can be taken with or without food.

You may need to break an Epivir tablet in half when giving this medicine to a child for HIV. Call your doctor if the child has any trouble swallowing the tablet.

If a child is using this medicine, tell your doctor if the child has any changes in weight. Lamivudine doses are based on weight in children, and any changes may affect your child's dose. Children who weigh more than 30 pounds (14 kilograms) should use the tablet form of lamivudine if possible. Lamivudine liquid may not be as effective.

Measure liquid medicine with the dosing syringe provided, or with a special dose-measuring spoon or medicine cup. If you do not have a dose-measuring device, ask your pharmacist for one.

The Epivir brand contains a higher dose of lamivudine than Epivir-HBV brand. Epivir is for treating HIV and Epivir-HBV is for treating hepatitis B. Each time you get a refill of this medication, be sure you have received the correct brand to treat your condition.

While using lamivudine, you may need frequent blood tests. Your kidney and liver function may also need to be checked. You may also need to have frequent HIV testing. If you become infected with HIV while you are taking lamivudine to treat hepatitis, the HIV could become resistant to antiviral medicines if not treated right away.

HIV/AIDS is usually treated with a combination of drugs. Use all medications as directed by your doctor. Read the instructions provided with each medication. Do not change your doses or medication schedule without your doctor's advice. Every person with HIV or AIDS should remain under the care of a doctor.

Store lamivudine at room temperature away from moisture and heat. Do not freeze. Keep the bottle tightly closed when not in use.

If you have hepatitis B you may develop liver symptoms after you stop taking lamivudine. Your doctor may want to check your liver function for several months after you stop using this medicine.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Lamivudine tablets (HBV) are indicated for the treatment of chronic hepatitis B virus (HBV) infection associated with evidence of hepatitis B viral replication and active liver inflammation [see Clinical Studies (14.1, 14.2)].

The following points should be considered when initiating therapy with Lamivudine tablets (HBV):

HIV Counseling and Testing

HIV counseling and testing should be offered to all patients before beginning treatment with Lamivudine tablets (HBV) and periodically during treatment because of the risk of emergence of resistant HIV-1 and limitation of treatment options if Lamivudine tablets (HBV) are prescribed to treat chronic hepatitis B infection in a patient who has unrecognized HIV-1 infection or acquires HIV-1 infection during treatment [see Warnings and Precautions (5.3)].

Dosage in Adult Patients

The recommended oral dosage of Lamivudine tablets (HBV) is 100 mg once daily.

Dosage in Pediatric Patients

The recommended oral dosage of Lamivudine (HBV) for pediatric patients aged 2 to 17 years is 3 mg per kg once daily up to a maximum daily dosage of 100 mg. The oral solution formulation of Lamivudine (EPIVIR-HBV) should be prescribed for patients requiring a dosage less than 100 mg or if unable to swallow tablets.

Dosage Adjustment in Adult Patients with Renal Impairment

Dosage recommendations for adult patients with reduced renal function are provided in Table 1 [see Clinical Pharmacology (12.3)].

Following correction of the dosage for renal impairment, no additional dosage modification of Lamivudine (HBV) is required after routine (4-hour) hemodialysis or peritoneal dialysis [see Clinical Pharmacology (12.3)].

There are insufficient data to recommend a specific dosage of Lamivudine (HBV) in pediatric patients with renal impairment.

Important Administration Instructions

Assessing Patients during Treatment

Patients should be monitored regularly during treatment by a physician experienced in the management of chronic hepatitis B. During treatment, combinations of events such as return of persistently elevated ALT, increasing levels of HBV DNA over time after an initial decline below assay limit, progression of clinical signs or symptoms of hepatic disease, and/or worsening of hepatic necroinflammatory findings may be considered as potentially reflecting loss of therapeutic response. Such observations should be taken into consideration when determining the advisability of continuing therapy with Lamivudine tablets (HBV).

The optimal duration of treatment, the durability of HBeAg seroconversions occurring during treatment, and the relationship between treatment response and long‑term outcomes such as hepatocellular carcinoma or decompensated cirrhosis are not known.

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including Lamivudine tablets (HBV) and other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors. Most of these reports have described patients receiving nucleoside analogues for treatment of HIV infection, but there have been reports of lactic acidosis in patients receiving Lamivudine for hepatitis B. Particular caution should be exercised when administering Lamivudine tablets (HBV) to any patient with known risk factors for liver disease; however, cases have also been reported in patients with no known risk factors. Treatment with Lamivudine tablets (HBV) should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).

Exacerbation of Hepatitis after Discontinuation of Treatment

Clinical and laboratory evidence of exacerbations of hepatitis have occurred after discontinuation of Lamivudine tablets (HBV) (these have been primarily detected by serum ALT elevations, in addition to the re-emergence of HBV DNA commonly observed after stopping treatment; see Table 4 for more information regarding frequency of posttreatment ALT elevations) [see Adverse Reactions (6.1)]. Although most events appear to have been self-limited, fatalities have been reported in some cases. The causal relationship of hepatitis exacerbation after discontinuation of Lamivudine tablets (HBV) has not been clearly established. Patients should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment with Lamivudine tablets (HBV). There is insufficient evidence to determine whether re-initiation of Lamivudine tablets (HBV) alters the course of posttreatment exacerbations of hepatitis.

Risk of HIV-1 Resistance if Lamivudine Tablets (HBV) Are Used in Patients with Unrecognized or Untreated HIV-1 Infection

Lamivudine tablets (HBV) contain a lower Lamivudine dose than the Lamivudine dose used to treat HIV-1 infection with EPIVIR tablets or with Lamivudine-containing antiretroviral fixed-dose combination products.

Lamivudine tablets (HBV) are not appropriate for patients co-infected with HBV and HIV-1. If a patient with unrecognized or untreated HIV-1 infection is prescribed Lamivudine tablets (HBV) for the treatment of HBV, rapid emergence of HIV-1 resistance is likely to result because of the subtherapeutic dose and the inappropriate use of monotherapy for HIV-1 treatment. HIV counseling and testing should be offered to all patients before beginning treatment with Lamivudine tablets (HBV) and periodically during treatment because of the risk of rapid emergence of resistant HIV-1 and limitation of treatment options if Lamivudine tablets (HBV) are prescribed to treat chronic hepatitis B in a patient who has unrecognized or untreated HIV-1 infection or who acquires HIV-1 infection during treatment.

Emergence of Resistance-Associated HBV Substitutions

In controlled clinical trials, YMDD-mutant HBV was detected in subjects with on-Lamivudine (HBV) re-appearance of HBV DNA after an initial decline below the solution-hybridization assay limit [see Microbiology (12.4)]. Subjects treated with Lamivudine (HBV) (adults and children) with YMDD-mutant HBV at 52 weeks showed diminished treatment responses in comparison with subjects treated with Lamivudine (HBV) without evidence of YMDD substitutions, including the following: lower rates of HBeAg seroconversion and HBeAg loss (no greater than placebo recipients), more frequent return of positive HBV DNA, and more frequent ALT elevations. In the controlled trials, when subjects developed YMDD-mutant HBV, they had a rise in HBV DNA and ALT from their own previous on-treatment levels. Progression of hepatitis B, including death, has been reported in some subjects with YMDD-mutant HBV, including subjects from the liver transplant setting and from other clinical trials. In clinical practice, monitoring of ALT and HBV DNA levels during treatment with Lamivudine tablets (HBV) may aid in treatment decisions if emergence of viral mutants is suspected.

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Lactic Acidosis and Severe Hepatomegaly

Advise patients that lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with use of Lamivudine tablets (HBV). Advise patients to contact their healthcare provider immediately and stop Lamivudine tablets (HBV) if they develop clinical symptoms suggestive of lactic acidosis or pronounced hepatotoxicity [see Warnings and Precautions (5.1)].

Severe Acute Exacerbation of Hepatitis after Discontinuation of Treatment

Inform patients that discontinuation of anti-hepatitis B therapy, including Lamivudine tablets (HBV), may result in severe acute exacerbations of hepatitis B including decompensation of liver disease. Advise patients not to discontinue Lamivudine tablets (HBV) without first informing their healthcare provider [see Warnings and Precautions (5.2)].

Risk of Development of HIV-1 Resistance in Patients with HIV-1 Co-infection

Counsel patients on the importance of testing for HIV to avoid inappropriate therapy and development of resistance to HIV. HIV counseling and testing should be offered before starting Lamivudine tablets (HBV) and periodically during therapy. Inform patients that if they have or develop HIV infection and are not receiving effective HIV treatment, Lamivudine tablets (HBV) may increase the risk of development of resistance to HIV medications. Advise patients that Lamivudine tablets (HBV) contain a lower dose of the same active ingredient (Lamivudine) as HIV drugs containing Lamivudine [see Dosage and Administration (2.1), Warnings and Precautions (5.3)].

Emergence of HBV Resistance

Inform patients that emergence of resistant hepatitis B virus and worsening of disease can occur during treatment. Patients should promptly report any new or worsening symptoms to their physician [see Warnings and Precautions (5.4)].

Hepatitis B Transmission

Advise patients that treatment with Lamivudine tablets (HBV) has not been shown to reduce the risk of transmission of HBV to others through sexual contact or blood contamination.

Pregnancy Registry

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

Missed Dosage

Instruct patients that if they miss a dose of Lamivudine tablets (HBV), 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)].

The brands listed are trademarks owned by or licensed to their respective owners and are not owned by or licensed to Prasco Laboratories. The makers of these brands are not affiliated with and do not endorse Prasco Laboratories or its products.

Manufactured for:

Prasco Laboratories
Mason, OH 45040 USA

by:

GlaxoSmithKline
Research Triangle Park, NC 27709

Manufactured under agreement from
Shire Pharmaceuticals Group plc
Basingstoke, UK

EPH-PS:2PI

PHARMACIST-DETACH HERE AND GIVE INSTRUCTIONS TO PATIENT

PRINCIPAL DISPLAY PANEL

NDC 66993-478-60

Lamivudine

Tablets (HBV) 100 mg

60 Tablets

Rx only

Each tablet contains 100 mg of Lamivudine.

See prescribing information for dosage information.

Store at 25oC (77oF); excursions permitted to 15o to 30oC (59o to 86oF) [see USP Controlled Room Temperature].

Do not use if printed safety seal under cap is broken or missing.

Manufactured for:

Prasco Laboratories

Mason, OH 45040 USA

Manufactured under agreement from Shire Pharmaceuticals Group plc

Basingstoke, UK

Made in Canada

Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Monitor therapy

Emtricitabine: LamiVUDine may enhance the adverse/toxic effect of Emtricitabine. Avoid combination

Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy

Trimethoprim: May increase the serum concentration of LamiVUDine. Monitor therapy

Manufacturer’s labeling:

All patients: Hepatic function, signs/symptoms of lactic acidosis; signs/symptoms of pancreatitis

HIV patients: Coinfection with HBV (prior to therapy); HIV viral load and CD4 count; immune reconstitution syndrome

Hepatitis B patients: Coinfection with HIV (prior to therapy); following discontinuation, monitor hepatic function closely with both clinical and laboratory follow/up for signs/symptoms of HBV relapse/exacerbation (continue for at least several months after stopping treatment)

Alternate recommendations:

Chronic Hepatitis B: HBV DNA and ALT (HBV DNA usually done every 3 months until undetectable and then every 3 to 6 months thereafter); HBeAg; anti-HBe (in patients who are HBeAg-positive to monitor for seroconversion); HBsAg; during therapy, consider monitoring amylase (if symptoms of pancreatitis) and lactic acid levels (if clinical concern); following discontinuation, monitor for recurrent viremia, ALT flares, seroreversion, and clinical decompensation every 3 months for at least 1 year (AASLD [Terrault 2016]). As antivirals do not eliminate the risk of hepatocellular carcinoma, continued monitoring for this complication is recommended in at-risk patients.