Drug profile of Tenof EM
Tenof EM tablets are used as anti-retroviral agent containing active components known as Emtricitabine & Tenofovir disoproxil fumarate which is pharmacologically categorized as nucleoside reverse transcriptase inhibitor.
Tenof EM is a fixed dose combination, dosage adjustment should not be considered.
Tenof EM is not a curable medicine; it is only prevent the progression of HIV infection into AIDS.
Tenofovir disoproxil fumarate is an available as a prodrug, which is converted into active form in vivo.
Emtricitabine is chemically classified as synthetic fluoro thiacytidine derivative with strong anti-retroviral activity.
Emtricitabine should not be used alone; it must be combined with other anti-retroviral medication for better action.
Tenofovir disoproxil fumarate has both anti-retroviral & anti-viral activity.
By combining with Emtricitabine, it is used only for HIV-1 infection.
Brand name: Tenof EM
Active substance: Tenofovir disoproxil fumarate & Emtricitabine
Mfg: Hetero healthcare
Strength: 300mg & 200mg respectively
Pack: 30 tablets in a container
Category: Anti-retroviral drugs
Prescribing information of Tenof EM
The most important indication of Tenof EM tablets is used against HIV-1 infectious condition.
Tenof EM is used alone or it should be used in combination of other anti-retroviral drugs like non-nucleoside reverse transcriptase inhibitor or protease inhibitors.
The major points should be taken into consideration before starting the therapy with Tenof EM;
Tenof EM should not be recommended, to be used as triple nucleoside drugs.
Tenof EM should not be concurrently used with Trustiva or Viraday tablets.
The indication of Tenof EM in therapy experienced patients should be accompanied by lab analysis & previous history of therapy of patients.
The other indication of Tenof EM is used in pre-exposure prophylaxis condition.
Mechanism of Tenof EM
Tenofovir DF is converted into tenofovir which is a parent form exhibits an anti-retroviral; activity.
Tenofovir is removes action by forbidding the HIV turn around transcriptase action by battling with deoxyadenosine 5' triphosphate (common substrate), after inclusion into DNA by DNA chain disposal.
When a nucleoside reverse transcriptase inhibitor agent inserted into viral DNA, this results as viral DNA synthesis is interrupt, this process is known as chain elimination.
Emtricitabine (FTC) has similar mechanism compared to TDF,
FTC is an analogue of cytidine (synthetic nucleoside), with the aid of cellular enzymes get phosphorylated into Emtricitabine 5’ triphosphate. This active form is essential for prohibition of HIV-1 reverse transcriptase.
Reverse transcriptase enzyme is used for copying the HIV RNA into new host viral DNA.
The active form of Emtricitabine is encountered with natural substrate called as deoxycytidine 5’ triphosphate and inserted into nascent DNA of suspected virus, which concludes as chain eliminator.
After oral administration of Tenof EM tablets, the absorption of Emtricitabine occurs very rapidly and reaches maximum plasma concentration at 1 to 2 hours.
Tenofovir DF has reaches maximum plasma concentration in 1.0 plus or minus 0.4 hour.
The oral bioavailability of Tenof EM;
Emtricitabine: 92%; Tenofovir DF: 25%
The volume of distribution of tenofovir is 1.3 plus or minus 0.6L/kg.
Tenofovir DF has very minimal protein binding capacity by <0.7% to human plasma protein; <7.2% to serum proteins.
Only 4% of Emtricitabine is binds to human plasma proteins
The metabolism of tenofovir DF has not assisted by cytochrome enzymes.
The metabolite of Emtricitabine is 3’ sulfoxide diastereomers & their glucuronic acid conjugate.
The elimination of Emtricitabine is occurs via glomerular filteration & active tubular secretion.
Nearly 86% of dose is appears in urine and 13% as metabolites.
The terminal half life of Emtricitabine is nearly 10 hours.
Nearly 80 to 70% of tenofovir eliminated in urine and elimination occurs via glomerular filteration & tubular secretion.
The terminal half life period of tenofovir DF is 17 hours.
The renal clearance of Emtricitabine is 213 plus or minus 89ml/min; 243 plus or minus 33ml/min.
When to take the Tenof EM
Tenof EM tablets should be administered with or without food.
Tenof EM tablets should not be broke, crush or chew.
Tenof EM contains;
Tenofovir disoproxil fumarate 300mg, Emtricitabine 200mg
Dosage regimens of Tenof EM
Before initiate the treatment, patient must be thoroughly investigate whether suspected with hepatitis B or not.
Kidney function test should be performed frequently and analysis the serum levels.
Conceal the patients for HIV-1 infection earlier to initiate the Tenof EM for HIV-1 PrEP for at least 3 months while taking Tenof EM.
Dose for HIV-1 infection:
The prescribed dose of Tenof EM is one tablet should be administered as a single dose.
Dose for pre exposure prophylaxis:
One Tenof EM tablet should be administered as a single dose.
For renal impairment patients, with mild condition no dosage adjustment should be required.
Regular monitoring of creatinine clearance & serum phosphorus should be performed for mild renal impaired patients.
CrCl: ≥50ml/min, the prescribed dose of Tenof EM is one tablet should be administered for every 24 hours.
CrCl: 30 to 49ml/min, the suggested dose of Tenof EM is one tablet should be taken for every 48 hours.
CrCl: <30ml/min: Tenof EM should not be used.
Tenof EM should not be suggested in HIV-1 uninfected individuals with estimated CrCl less than 60ml/min for HIV-1 PrEP
Tenof EM caused side effects
The common adverse effects;
Immune reconstitution syndrome
Depletion of bone mineral density
New outbreak or aggravation of renal impairment
Exacerbation of hepatitis B
Lactic acidosis or hepatic steatosis
Common side effects;
Respiratory tract infection
Increased creatine kinase
Increased serum amylase
Increased alkaline phosphatase
Increased AST, ALT
Increased blood glucose
Post marketing reports;
Drug- drug interaction
1. Tenof EM co administered with Didanosine causes increasing concentration of Didanosine and concludes as elevation of adverse effects associated with Didanosine.
Avoid this condition; consume Didanosine buffered tablet with Tenof EM should be taken under fasted state.
In adults patient weight of >60kg, the dose of Didanosine should be decreased to 250mg, while concurrently used with Tenof EM.
2. Atazanavir combined with Tenof EM tablets leads to cause increasing the effect of concentration of components present in Tenof EM. This combination results as elevates the adverse related to Tenof EM.
To resolve the problem by stopping the Tenof EM tablets immediately.
A Tenofovir lead to cause depletes the AUC & Cmin value of atazanavir. In case of combination of Tenof EM with atazanavir, the dose of atazanavir 300mg with ritonavir 100mg should be given for this condition. Without ritonavir, atazanavir should not be allowed to use in case of this combinational study with Tenof EM.
3. Lopinavir/ ritonavir combination tablets combined with Tenof EM causes elevation of tenofovir concentration.
In this condition patient should be monitored frequently for adverse effects associated with Tenvir. To over the ill effects stop the Tenof EM tablets.
4. Tenof EM tablets co administered with the drugs which affect the renal functions may leads to causes increasing the level of both tenofovir disoproxil fumarate & Emtricitabine.
Food drug interaction
Minor food drug interaction is possible
Diet should be consulted with medical adviser and follow the diet chart.
Some hypersensitivity reactions may produces if patient is contraindicated to the components present in the Tenof EM tablets.
1. Lactic acidosis or hepatic steatosis: In case of using nucleoside analogues, this fatal case is produced. This condition is majorly present in women and causes obesity.
Care should be taken during the therapy used with nucleoside analogues.
Therapy should be interrupt until resolved this condition.
In severe, treatment should be discontinued.
2.Co infection of HIV-1 & HBV: Patient before receiving the anti-retroviral agents must be examine properly whether the patients may suspected with hepatitis B viral infection or not.
The potency of Tenof EM for chronic hepatitis B infection has not been evaluated.
The potency of Tenof EM for co infected HIV-1 & HBV patients also not been established.
In this condition, after completion of treatment with Tenof EM patients may have chance of acquiring severe aggravation of hepatitis B infection.
To overcome the problem, initiation of hepatitis B anti-viral agents should be warranted.
3. Renal impairment, this severity arises due to combinational study of Tenof EM with drugs affecting the renal function. Kidney function test should be performed.
Concurrent use of Tenof EM & nephrotoxic agents should be avoided.
Tenof EM tablets should not be used in patients with creatinine clearance of less than 30ml/min or hemodialysis occurred patients.
4. Tenof EM should not be concurrently used with Trustiva, Viraday and also the drugs containing lamivudine.
Tenof EM should not be used with Adefovir dipivoxil
5. Depletion of bone mineral density, loss of calcium occur leads to osteomalacia
Bone mineral density should be monitored and vitamin D supplements should be provided.
6. Reaccumulation of fat causes obesity, peripheral wasting, facial wasting, breast enlargement, etc.
Provide supportive measures and discontinue the therapy.
7. Immune reconstitution syndrome, Discontinue the treatment.
8. Loss of virological effects occurs during the use of triple nucleoside regimens.
Pregnancy and lactation
Tenof EM pregnancy category B
Tenof EM should be used very cautiously by the patient’s only getting advice from the medical practitioner.
Before the treatment, the risk benefits associated with Tenof EM should be counseled to the treatment getting patient.
Avoid becoming pregnant during the treatment.
Breast feeding should not be allowed for avoiding the spreadness of infection from infected mother to baby through milk.
Storage and handling
Tenof EM tablet container should be kept at 25oC
Protect from light
Container should be tightly closed after use
Do not use the tablet, if seal of container should be opened or broke.
Keep away from moisture & heat.
Tenof EM is an anti-retroviral medicine, In case of missed dose patient should be consult with physician and follow the instructions.
Maintain the regular dosing schedule
Avoid the incidence of missed dose, which may leads to over dosage and cause severe adverse effects.
In case of over dosage of Tenof EM, patient must be;
Provided with general supportive management
Monitor the signs & symptoms associated with over dosage of Tenof EM
Hemodialysis process should be followed for removing the absorbed dose from the body.
Almost 30% of Emtricitabine dose should be eliminated from the body after 3 hours dialysis process.
Tenofovir should be removed with range of 54% after 4 hours session of dialysis.