Telura (Tenofovir Disoproxil +Lamivudine +Efavirenz)

DESCRIPTION

A Telura tablets contain three anti-retroviral agents like tenofovir DF, lamivudine & efavirenz.

Telura tablets are not used for curing the infection, but it is involved in reduction of advancement of HIV-1 into AIDS. Telura is used to reduce the HIV viral production

MECHANISM OF ACTION

The major mechanism of Telura is involved in prohibition of reverse transcriptase enzyme. The enzyme is responsible for HIV viral production.

Lamivudine

Lamivudine after absorption, undergoes phosphorylation intracellularly leads to form an active moiety known as lamivudine 5’ triphosphate (nucleoside analogue). This metabolite gets inserted into DNA of HIV virus which is aided by HIV RT & HBV polymerase.

Efavirenza

The anti-viral activity of Efavirenz is due to formation of active triphosphate form of efavirenz by undergoing intracellular conversion. This formed active metabolite gets inserted into viral cells by RT causes inhibition of newly formed virions by obstruct the DNA copies.

Tenofovir DF

This prodrug converted into tenofovir by diester hydrolysis and gets phosphorylated to from triphosphate form (nucleoside analogue), inserted into viral cells by HIV RT enzyme causes chain termination. Efavirenz: chain terminator causes prohibition of new viral DNA synthesis Tenofovir DF: chain terminator Lamivudine: chain terminator

PHARMACOKINETICS

ABSORPTION

Lamivudine get absorbed very quickly. The bioavailability of lamivudine is occurs by 86% plus or minus 16%. Tenofovir bioavailability by 25% & raises up to 40% by administering with food. Time to maximum plasma concentration of tenofovir is 1.0 plus or minus 0.4 hour

DISTRIBUTION

Tenofovir: It has low protein binding capacity by 0.7% to human plasma protein or <7.2% to serum proteins. Lamivudine has human plasma protein by <36% The efavirenz binding nature of is nearly 99.5 to 99.75%.

METABOLISM

The metabolism of Telura is occurs hepatically. Efavirenz get metabolized by using cytochrome P450 isoenzymes to form metabolites. Lamivudine get metabolized by undergoing biotransformation. Tenofovir metabolism is not induced by cytochrome isoenzymes.

ELIMINATION

The tenofovir DF elimination is occurs via glomerular filteration & active tubular secretion. Efavirenz get eliminated via urine Lamivudine eliminated by urine. The half lives of Telura ; Tenofovir: 17 hours Efavirenz: 40 to 55 hours Lamivudine: 5 to 7 hours

DOSAGE MANAGEMENT

DOSAGE & ADMINISTRATION OF TELURA

Before begin the therapy with Telura , patient should be examined for presence of HBV infection or not. kidney function & liver function test should be performed. The recommended dose of Telura is one tablet should be administered as once daily. Telura is a three drug fixed dose combination; it should be administered on an empty stomach. This tablet should be consumed at bed time due to reducing the neurological problems. Telura should not be prescribed for; Patients who have creatinine clearance less than 50ml/min With severe renal impairment Hemodialysis patient Telura should not be used for; Moderate & severe liver impairment patients

WARNING & PRECAUTION

LACTIC ACIDOSIS

Prevent the problem by measuring the hepatic enzymes level In severe condition stop the Telura treatment.

AGGRAVATION OF HBV

After stopping of the anti-HBV agents, reactivation of HBV infection occurs. Inhibits the problem by investigating the patient’s history whether suspected with HBV infection or not.

LOSS OF VIROLOGICAL EFFECTS

Telura is a three drug fixed dose combination; there is a chance of occurring resistance. Monitor the patient’s condition frequently.

NERVOUS PROBLEM

Reduce the problem by giving Telura at bed time on an empty stomach.

EMBRYO FETAL DAMAGE

Telura is contraindicated to pregnancy condition

SKIN PROBLEMS

Severe hypersensitivity reactions are produced during Telura therapy. Prevent the problem by providing general supportive measures.

LIVER TOXICITY

Monitor the liver function test Maintain the hepatic enzymes In severe condition, stop the treatment

BONE DEFECTS

During the treatment, loss of calcium levels occur causes osteomalacia Prevent the problem by providing vitamin D supplements.

IMMUNE RECONSTITUTION SYNDROME

This fatal case is frequently occurred in anti-retroviral therapy. In serious condition stop the Telura tablets. Fat redistribution, discontinue the Telura tablets QT prolongation reduced by avoiding the concomitant use of Telura with drugs which may extends the QT intervals.

SIDE EFFECTS

SIDE EFFECTS OF TELURA

Lactic acidosis Aggravation of HBV Renal damage Psychiatric problems Nervous problems Skin related problems Liver toxicity Hepatic decompensated cirrhosis Pancreatitis Bone defects Immune reconstitution syndrome Redistribution of fat The most common side effects; Pain in Head, pain, vomiting, abdominal pain, back pain, asthenia, diarrhea, nausea, dyspepsia, fever , lipodystrophy, arthralgia, insomnia Lab abnormalities; Cholesterol is Increased, elevation of creatine kinase, increased AST & ALT, Hematuria, neutropenia, increased serum amylase

DRUG INTERACTION

Telura should not be combined with other anti-retroviral drugs. Telura should not be combined with QT prolonged drugs Telura with drugs affecting the renal functions causes increased concentration of tenofovir and leads to increase the adverse effects. Telura should not be combined with cannabinoids receptors Telura with CYP3A inducers causes increased clearance of Telura & leads to reduce the plasma concentration. Telura with warfarin causes fluctuation in prothrombin time & INR values. Telura with anti-convulsants causes reduced effect of concentration of these drugs. Telura with anti-fungals, anti-depressants, or anti-infective causes reduced effect of concentration of these drugs. Telura with anti-malarial, anti-mycobacterials, calcium channel blockers, or lipid lowering drugs causes decreased effect of concentration of these drugs.

CONTRAINDICATION

Telura is contraindicated to patients who are concomitantly received elbasvir & grazoprevir. Hypersensitivity reactions are produced due to patients is contraindicated to the component of Telura.

PREGNANCY & LACTATION

Pregnancy category of lamivudine: C Pregnancy category of efavirenz: D Pregnancy category of tenofovir: B Telura should not be used during pregnancy condition; it may leads to embryo fetal damage Breast feeding should not be allowed.

STORAGE 

Do not self medicate the Telura tablets Storage Telura container should be kept at temperature below 30°C Store the container away from heat, moisture & light

MISSED DOSE

Telura is a three drug mixed dose regimen, caution should be taken during therapy using with Telura tablets. In case of missed dose, patients must consult with medical practitioner & follow their instructions. Maintain the regular dosing schedule Avoid the missed dose if possible