Tulavir

Uses

This is used for the treatment of:

• Chronic hepatitis B virus infection in adults
• HIV infected adults in combination with other anti retroviral agents

How Tulavir works

Once tenofovir is activated by a bi-phosphorylation it acts as an antiviral acyclic nucleoside phosphonate. It is a potent inhibitor of the viral reverse transcriptase with an inhibitory constant of approximately 0.022 micromolar.

Once activated, tenofovir acts with different mechanisms including the inhibition of viral polymerase causing chain termination and the inhibition of viral synthesis. All these activities are attained by its competition with deoxyadenosine 5'-triphosphate in the generation of new viral DNA. Once tenofovir is incorporated in the chain, it induces a chain termination which in order inhibits viral replication. The safety of tenofovir relies on its low affinity towards the cellular DNA polymerase including the mitochondrial DNA polymerase gamma.

Dosage

Tulavir dosage

The recommended dose of Tenofovir in chronic hepatitis B virus infection in adults 18 years of age and older with adequate renal function is 300 mg once daily with or without food.

Side Effects

The most common side effects are nausea, vomiting, diarrhea and flatulence.

Toxicity

There haven't been reports regarding the LD50 of the parent compound nor the effects of an overdose. However, based on the reports with the derivative that most rapidly transforms into tenofovir, tenofovir disoproxil, it is recommended to monitor overdose patients. As well, it is widely known that tenofovir is efficiently removed by hemodialysis.

Administration of high doses of tenofovir has been reported to produce bone toxicity reported as osteomalacia and reduced bone mineral density and to produce some degree of renal toxicity.

To know more about the carcinogenicity and mutagenic potential of tenofovir, as well as the effect on fertility, please visit the drug entries for the derivatives tenofovir disoproxil and tenofovir alafenamide.

Precaution

Co-administration with other drugs: Tenofovir should not be administered concurrently with Emtricitabine & Tenofovir combination or Adefovir Dipivoxil.

Lactic Acidosis & Severe Hepatomegaly with Steatosis: Though the risk of occurrence of lactic acidosis is low for Tenofovir, treatment should be suspended in any patient who develops lactic acidosis or hepatotoxicity.

Exacerbation of hepatitis after discontinuation of treatment: Discontinuation of Tenofovirtherapy may be associated with severe acute exacerbation of hepatitis.

Interaction

Co-administration of Tenofovir with anti-retroviral, entecavir, lamivudine, methadone, oral contraceptives, ribavirin and tacrolimus did not result in significant drug interactions. The effects of co-administration of Tenofovir with other drugs that are renally eliminated or are known to affect renal function have not been evaluated.

Volume of Distribution

Accumulation of tenofovir in plasma is related to the presence of nephrotoxic effects. It is reported that tenofovir presents a volume of distribution of 0.813 L/kg.

Elimination Route

Tenofovir as the active moiety presents a very low bioavailability when orally administered. Hence, the administration of this active agent is required to be under its two prodrug forms, tenofovir disoproxil and tenofovir alafenamide. This reduced absorption is suggested to be related to the presence of two negative charges among its structure. This negative charge limits its cellular penetration, and its passive diffusion across cellular membranes and intestinal mucosa hindering its availability for oral administration.

Intravenous tenofovir has been shown to produce a maximum plasma concentration of 2500 ng/ml with an AUC of 4800 ng.h/ml.

Half Life

The reported half-life of tenofovir is of 32 hours.

Clearance

The clearance of tenofovir is highly dependent on the patient renal stage and hence the clearance rate in patients with renal impairment is reported to be of 134 ml/min while in patients with normal function the clearance rate can be of 210 ml/min.

Elimination Route

Tenofovir is eliminated in the urine by tubular secretion and glomerular filtration. The elimination of this compound is driven by the activity of the human organic anion transporters 1 and 3 and its secretion is mainly ruled by the activity of the multidrug resistance-associated protein 4.

Pregnancy & Breastfeeding use

Pregnancy: Pregnancy category B. It should be used during pregnancy only if clearly needed.

Lactation: It is not known whether it is excreted in human milk. Mothers should be instructed not to breast feed if they are taking Tenofovir.

Contraindication

Tenofovir is contraindicated in patients with known hypersensitivity to Tenofovir or any component of the product.

Special Warning

Pediatric use: Safety and effectiveness of Tenofovir in pediatric patients below the age of 18 years have not been established.Geriatrics use: Clinical studies of Tenofovir did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. But care should be taken in dose selection, and it may be useful to monitor renal function.Renal Impairment: Haemodialysis patients: 300 mg once every 7 days or after a cumulative total of 12 hr of dialysis.

• CrCl (10-29 mL/min): 300 mg 72-96 hrly.
• CrCl (30-49 mL/min): 300 mg 48 hrly.

Hepatic impairment

: No dose adjustment is required in patients with hepatic impairment.

Acute Overdose

There is no experience of Tenofovir overdose reported in patients

Storage Condition

Store in a cool and dry place, protected from light and moisture. Keep the medicine out of the reach of children.

Innovators Monograph

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