Lamidin is a preparation of Lamivudine. Lamivudine is a nucleoside analogue with in vitro activity against HBV. Lamivudine is an obligate chain terminator, preventing DNA chain elongation, and thus preventing HBV replication. Laminaton, praventing DNA chain elongation, and thus prevanting HBV replication. Lamivudine has potent inhibiotory activities againtst HBV in vitro ,as well as is animal models. Lamivudine has exhibited nosinificant cytotoicity against a rage of different cell lines, and has little effect on mammalian mitochondrial DNA content. Lamivudine has been well tolerated with no dose limiting toxicities.
 

Lamivudine is indicated for the treatment of patients with chronic hepatitis B with evidence of HBV replication.

The recommended dose is 100 mg orally once daily for adults over 16 years of age. Treatment should be continued at least until HBeAG or HBeAG seroconversion.
 

No interaction studies were conducted based on data from in vitro pre-clinical studies to investigate the effects of possibly co-prescribed drugs on absorption.

Potential renal clearance interactions, assessed using the isolated rat perfused kidney were studied. The renal model pointed to a potential interaction with triemtiporim, one of the consutituent fo co-trimoxazol. A follow-up study in man showed an increase in lamivudine AUC by approximatley 40% but no change in sulfamethpxazole or trimethoprim pharmacokinetic data when administrated concurrently.

No Significant pharmacokinetic interaction was seen with recombinant alfainterferon, a commonly used immunotherapy for chronic hepatitis B in two studies.

Clinical significant drug-drug interaction between systemic lamivudine and other drugs are unlikely. Only drugs excreted predominantly via active renal secretin with a narrow therapeutic index would be potential candidates, a priori, for a drug-drug interaction and should be considered on an individual basis. Given the excellent safety profile of lamivudine exposure following 100 mg once-daily are of little clinical concern.

Safety : The safety profile of lamivudine has been established in the clinical programme. The nature and incidence of adverse events is similar to placebo in patients with compensated liver disease. With the exception of post treatment ALT elevation which occurred more more commonly in lamicudine treated petients and were generally transient, asymptomatic and resolved spontaneously.

Use of lanivudine is contra-indicated in patients with know hypersensitivity to lamivudine or to any ingredient of the preparation. Cases of panreatitis have occurred rarely. Treatment with lamivudine should be stopped immediately if clinical signs, symptomes or laboratory abnormalities suggestive of pancreatitis occur.

There are insufficient data on the use of lamivudine in children under the age of 12 years.

Administration of lamivudine is not recommended during the first 3 months of pregancy.

In patients with moderate-severe renal impairment, the terminal plasma half-life of lamivudine is increased clearance. The dose should be adjusted.

Lamivudine should be used with cautuion in patients with advanced cirrhotic liver disease due to chronic Hepatities B infection, as there is a small risk of rebound hepatitis if tratment is discontinued.

Interaction with other medicaments and other forms of interaction: The likelihood of metabolic interactiosn is low due to limited metabolism and plasma protein binding and almost complete renal clearance.

The possibility of interactions with other drugs administered concurrnetly should be considered, particularly when the mian route of elimination is active renal secretion via the organic cationic transport system e.g. trimethoprim. Other drugs (e.g. ranitidine, climetidine) are eliminated only in part by this mechanism and were shown not to interact with lamivudine. The nucleaside analogues (e.g. didanosine and zalcitable) like zidovudine are not eliminated by this mechanisms and are unlikely to interact with lamivudine.

Administration of prophylactic doses of co-trimoxazole results in a 40% increase in lamivudine exposure, because of the trimethoprim component: the sulfamethoxazole component did not interact. However, unless the patient has renal impairment, no dosage adjustment of lamivudine is necessary. CO-adminstration of lamivudine with high doses of co-trimoxazole for the treatement of Pneumocystis carini pneumonia (PCP) and toxoplasmosis should be avoided. Lamivudine has no effect on the pharmacokinetics of co-trimoxazole. Lamivudine metabolism dose not involve CYP3A, making interactions with drugs metabolised by htis system (e.g. protease inhibitors) unlikely.

Co-adminstration of lamivudine with intravenous ganciclovir or foscarnet is not recommended until information is available.

Other Information :
Unlike interferon Alfa, lamivudine can be used in patients with decompensated liver disease. treatment should be continued if there is no loss of efficacy and until adequate seroconvertion is achieved; it is continued long-term in decompensated liver disease. Hepatitis B viruses with reduced susceptibility to lamivudine have emerged following extended therapy. In patients with HIV infection not requiring anti-retro viral therapy, the use of lamivudine alone for chronic hepatitis B may give rise to lamivudine resistant HIV.

Pregnancy
The safety of lamivudine in human pregnancy has not been established. Reproductive studies in animals have not shown evidence of teratogenicity, and showed no effect on male of female fertility. Lamivudine induces early embryolethality when administered to pregnant rabbits at exposure levels comparable to those achieved in man. Lamivudine crosses the placenta in animals but there is no information on placental transfer in humans.
Although animal reproductive studies are not always predictive of the human response, administration during the first three months of pregnancy is not recommended.
Lactation
A study in lactating rats showed that, following oral administration, lamivudine was concentrated four fold and excreted in in the milk,it is not known if lamivudine is excreted in human breast milk. Since the drug may pass into breast milk, it is recommended that mothers taking lamivudine do not breast feed their infants.
 

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 cannot 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 patient's ability to drive or operate machinery.
 

Adverse events which have been commonly reported are headache, malaise, fatigue, nausea, diarrhea, vomiting, abdominal pain or cramps, insomnia, cough, nasal symptoms and musculoskeletal pain.
Cases of pancreatitis and peripheral neuropathy (or paraesthesia) have been recorded, although no relationship to the dose of lamivudine has been noted.
Neutropenia and anaemia (both occasionally severe) have occurred in combination with zidovudine. Thrombocytopenia, transient rises in liver enzymes (AST,ALT) and rises in serum amylase have been reported .
 

Administration of lamivudine at very high dose levels in acute animal studies did not result in any organ toxicity. Limited data are available on the consequences of ingestion of acute overdoses in humans. No fatalities been identified following such overdose.
Since lamivudine is dialysable, continuous haemodialysis could be used in the treatment of over dosage, although this has not been studied.
 

Keep in a cool dry place, away from light. Keep out of reach of children.
 

Lamidin tablet : Box containing 1 strip of 10 tablets. Each film coated tablet contains lamivudine INN 100 mg. 



Manufactured by:
ESKAYEF BANGLADESH LTD
DHAKA, BANGLADESH
® REGD.TRADEMARK