Heplav

HEPLAV
LAMIVUDINE 
TABLET

COMPOSITION 
Each tablet contains:
Lamivudine .................................. 100 mg

INDICATION
Lamivudine is indicated for the treatment of patients with chronic hepatitis B infection with evidence of hepatitis B viral replication.

POSOLOGI AND METHOD OF ADMINISTRATION
The recommended dosage for adults is 100 mg once daily. The dose in children has not yet been established. Treatment discontinuation may be considered when HBe and HBs antigen seroconversion occurs. There is insufficients data to confirm that seroconversion will be sustained once treatment with Lamivudine is stopped.
Patient compliance should be monitored while on therapy. If lamivudine is discontinued patients should be observed carefully as there may be a small risk of exacerbation of hepatitis in same patients. .
Lamivudine should be initiated and monitored by a physician experienced in the management of chronic hepatitis infection.

CONTRAINDICATION
Lamivudine is contraindicated in patients with known hypersensitivity to lamivudine or to any ingredient of the preparation.


SPECIAL WARNINGS AND SPECIAL PRECAUTIONS FOR USE

-	Warnings
	When stopping treatment with Lamivudine (eg due to pregnancy, creatine clearance falling below 30 ml/min or other reason) patients should be monitored carefully. This exacerbation of hepatitis could potentially be more severe in patients with decompensated liver disease. If an exacerbation of hepatitis occurs consideration should be given to restarting treatment with Lamivudine. Lamivudine is really c1eared and dose reduction is necessary for renally impaired patients with a creatinine clearance of ‹ 30 ml/min. There is currently no formulation available to allow appropriate dosing of the patients. For patients whose renal function declines to a creatinine clearance of ‹ 30 ml/min while on treatment, the physician will need to consider the risk/ benefit to patients of increased serum lamivudine levels by continuing treatment, and the risk of an exacerbation of hepatitis occurring if treatment is stopped.
-	Precaution for use
	Patients who are HIV positive, co infected with hepatitis B virus and are receiving treatment with Lamivudine in combination with other antiretroviral agents for HIV, should continue treatment with the regimen prescribed to HIV infection (150 mg twice daily). These patients are also at risk of an exacerbation of their hepatitis if their lamividune treatment for HIV is discontinued. The clinical and virological status of patients should be monitored regularly during treatment by a physician experienced in the management of hepatitis B infection. There is no information available on maternal-foetal transmission of hepatitis B virus in pregnant mothers receiving treatment with Lamivudine. The standard recommended procedures for hepatitis B virus immunization in infants should still be followed. Patients should be advised that therapy with Lamivudine has not been proven to prevent the risk of transmission of hepatitis B virus to others, through sexual contact or blood contaminations. Appropriate precautions should still be taken. The efficacy of lamivudine is hepatitis B patients co-infected with hepatitis C and D is unknown.
-	Interaction with other medicaments and other forms of interactions
	Lamivudine is predominantly eliminated by active organic cationic secretion. The potential for interactions with concurrently administered drugs sharing this pathway as a major elimination route (eg trimethoprim) should be considered, particularly if the patients has renal impairment. Other drugs (eg ranitidine, cimetidine) are eliminated only in part by this mechanism and were shown not to interact with lamividune. Drug shown to be predominately excreted either via the active organic anionic pathway, or by glomerular filtration ( e g ganciclovir, foscarnet) are unlikely to yield clinically significant interactions with lamivudine. Administration of trimethoprim, a constituent of cotrimoxazole, causes an increase in lamivudine exposure of about 40 %. Lamivudine has a high therapeutic ratio and this increase is not considered clinically relevant unless the patient has renal impairment. Lamivudine has no effect on the pharmacokinetics of cotrimoxazole. There is no known adverse interaction with alpha interferon. There are no observed clinically significant adverse interactions in patients taking Lamivudine concurrently with commonly used immunosuppressant drugs (eg cyclosporine A).
-	Pregnancy and lactation
	Administration for Lamivudine during the first three months of pregnancy is not recommended. Lamivudine has proven to be safe and well tolerated in HIV-infected pregnant women at dose up 300 mg twice daily, administered from week 38 of pregnancy. Lamivudine was shown to cross the placenta with maternal / neonate serum concentration ratio of about 1.0 established at birth. The presence of lamivudine in amniotic fluid was also established. There is no safety information available on infant breastfed by mothers treated with Lamivudine. In breast milk samples taken in the first week post-partum, lamivudine was present overall in similar concentrations to those seen in serum (range 1 - 8 mcg/ml). Ingestion of lamivudine via this route would not provide concentration sufficient to provide anti-viral protection. Breast feeding should not be discouraged unless the potential risk to the baby considered to outweigh the benefits of treatment with lamivudine to the mother.
-	Effect on the ability to drive and operate machinery
	There have been no studies to investigate the effect of lamivudine on driving performance or the ability to operate machinery. Further, a detrimental effect on such activities would not be predicted from the pharmacology of the drug. Nevertheless, the clinical status of the patient and the adverse event profile of Lamivudine should be borne in mind when considering the patients ability to drive or operate machinery.
-	Undesirable effects
	Lamivudine appears to be well tolerated. The most commonly reported adverse events reported were symptoms associated with upper respiratory tract infection, headache, nausea, malaise, abdominal pain and diarrhoea.
-	Overdose
	If overdosage occurs the patients should be monitored, and standard supportive treatment applied as required. Since lamivudine is dialyzable, continuous haemodyalisis could be used in the treatment of overdosage, although this has not been studied.

PHARMACOLOGICAL PROPERTIES
Lamivudine is an antiviral agents which is active against hepatitis B virus (HBV). Lamivudine is metabolised by both infected and uninfected cells to the triphophaste (TP) derivate which is the active form of the parent compound. The intracellular half life of the triphosphate in hepatocytes is 17 - 19 hour in vitro. Lamivudine - TP acts as an inhibitor of, and substrate for the HBV viral polymerase. The formation of further viral DNA is blocked by incorporation of lamivudine -TP into the chain and subsequent chain termination.
Lamivudine -TP does not interfere with normal cellular doxynucleotide metabolism. It is also only a weak inhibitor of mammalian DNA polymerases alpha and beta. Furthermore, lamivudine - TP has little effect on mammalian cell DNA content.
In assays relating to potential drug effect on mitochondrial structure, DNA content, and function, lamivudine lacked appreciable toxic effects.
It has a very low potential to decrease mitochondrial DNA content, is not permanently in-corporated into mitochondrial DNA, and does not act as an inhibitor of mitochondrial DNA polymerase gamma.

PACKAGING / REG.NO
Box, 1 bottle @ 30 tablets / DKL 1112425310A1

STORAGE
Store at temperature below 30°C, protected from light.

ON MEDICAL PRESCRIPTION ONLY
HARUS DENGAN RESEP DOKTER

PT. KIMIA FARMA
JAKARTA - INDONESIA

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