Trade name : Naivex Tafero EM
Active ingredient :Dolutegravir; Tenofovir Alafenamide & Emtricitabine
Strength availability : 50MG; 25MG & 200MG respectively
Manufactured by : Hetero healthcare
Package : 30 tablets in a container
Category : Anti-retroviral drugs
Naivex and Tafero EM are two major product involved in the treatment of HIV-1 infection.
Naivex tablets are containing an active substance known as Dolutegravir, which is a inhibitor of human immunodeficiency virus Integrase strand transmission. Naivex tablet is a prescription medicine, which is endorsed by FDA for the HIV-1 therapy. Dolutegravir is not used as such, it may combine with another anti-retroviral medicines. Naivex tablets are not able to cure the infection, only it may reduce the spreading and depletes HIV counts in the human body.
Tafero EM is also categorized as anti-retroviral medicine, which is exhibited by two prime components like Tenofovir Alafenamide and Emtricitabine Tafero EM is also used for the HIV-1 infection, it will not cure, but it stops to convert as serious ill like AIDS. Tafero EM tablets are used by combining with other anti-retroviral drugs. Both Naivex and Tafero EM are pharmacologically categorized as; Naivex: Integrase prohibitor Tafero EM: Reverse transcriptase inhibitor.
In Naivex and Tafero EM dosage considers,
In Tafero EM, preceding to initiate the therapy, patient must be examined thoroughly whether hepatitis B virus infection is suspected in the particular patient or not.
Creatinine clearance, urine glucose, urine protein value should be investigated.
• Naivex containing 50mg of Dolutegravir
• Tafero EM containing Tenofovir Alafenamide 25mg and Emtricitabine 200mg
The dosage recommendation
The usual dosage of Naivex and Tafero EM is one tablet to be taken as a single dose as orally. Both are administered with or without food. The recommended dosage of Tafero EM is applicable for adults and pediatric with the weight of 25kg or creatinine clearance larger than or equal to 30ml per minute. Tafero EM should not be used in severe renal damage patients whose creatinine clearance value is below 30ml/min.
Recommendation for Naivex
In adults: INSTI (Integrase strand transfer inhibitor)
For new patients or experienced INSTI new or virologically restrained :
The recommended dose of Naivex 50mg should be taken as once a day
For new or experienced INSTI new by combining with UGT1A or CYP3A inducers :
The recommended dosage of Naivex is 50mg should be given as two times a day
For INSTI already treated with certain INSTI related resistance alternatives :
The recommended dosage of Naivex is 50mg should be given as two times a day
In pediatric: The recommended dosage of Naivex for 30 to less than 40kg patients: 35mg should be taken as a once a day For 40kg or greater patients: The prescribed dosage is 50mg once daily.
Maximum plasma concentration time of Emtricitabine is 3 hours; TAF is 1 hour
TAF & Emtricitabine bounds to human plasma protein at 80% & <4% respectively
The cause of protein binding data for TAF & Emtricitabine is occurs ex-vivo & in vitro respectively.
The blood plasma ratio of TAF & Emtricitabine is 1.0 & 0.6 respectively
The metabolism of TAF & Emtricitabine;
TAF: Metabolized by cathepsin A, carboxyl esterase 1 or CYP3A at minimal level.
Emtricitabine metabolism is occurred via biotransformation.
The main excretion of TAF & Emtricitabine are occurs through; >80% of drug get metabolized and through renally respectively.
The terminal half life of;
TAF: 0.51 hour
Emtricitabine: 10 hours
Emtricitabine: 70% of metabolite excreted through urine; 13.7% via feces
TAF: <1% in urine; 31.7% feces.
The pharmacokinetic property of Naivex :
Maximum plasma concentration time of Dolutegravir is 2 to 3 hours The steady state level reaches within 5 days Dolutegravir is highly bound to human plasma protein at 98.9% The terminal half life of Dolutegravir is 14 hours. The major route of elimination is urine & as an unchanged form through feces.
Naivex (Dolutegravir) contains hostile to viral property against HIV write I contamination.
Naivex is an Integrase inhibitor, which can ready to restrict HIV cell development by meddling with Integrase authoritative to the dynamic site and barricade of strands exchange step happened.
The viral DNA combination into have cells get halted
This exchange procedure is in charge of HIV cell increase cycle.
This prompts hindrance of viral action
Tafero EM : Tafero EM has two parts which shows hostile to retroviral action, against HIV TAF and Emtricitabine TAF: TAF is a prodrug, change over to tenofovir by hydrolysis. TAF has cell penetrability property which will attack into the cells and changed over into tenofovir through hydrolysis utilizing cathepsin A as an impetus. Tenofovir again under goes phosphorylation to deliver tenofovir diphosphate, a functioning metabolite of tenofovir by cell kinase. Tenofovir diphosphate, shows its hostile to retroviral action against HIV by embeddings into viral DNA with the assistance of HIV turn around transcriptase and restricts HIV replication and causes chain impediment Emtricitabine is additionally changed over into Emtricitabine 5 triphosphate, this metabolite is engaged with HIV reproducing restraint. Emtricitabine 5' triphosphate is battling with common substrate deoxycytidine 5' triphosphate and embedded into viral DNA and causes chain end
For Tafero EM
The most serious effects may occur; Aggravation of hepatitis B in HBV/HIV co infected patients: Before starting the therapy patients should be investigated properly, if HBV infection is already present or not. Immune restructuring syndrome: Some immune reconstituting syndrome is occurred during the initial stage of anti-retro viral therapy. Out breaking or worsening of renal damage: Avoid concurrent use of drugs reducing renal function with Tafero EM and monitor the renal functions frequently during the therapy. Lactic acidosis or hepatomegaly with steatosis: Discontinue the therapy
Hypersensitivity reaction: This may occur due to contraindication Liver damage: Elevation of AST & ALT levels causing liver damage; To avoid this problem monitor the patients with frequent liver function test. Lack of virological response during drug interaction: The Resistance of Naivex may occur in some patients during concomitant use with some drugs. Immune reconstitution syndrome: Some immune restructuring ailment is occurred during the initial stage of anti-retro viral therapy
The pregnancy category of Dolutegravir is B Pregnancy category of TAF & Emtricitabine is B Using Naivex & Tafero EM in pregnancy condition with caution, only after knowing the risk factors to the fetus of these products In Some patients placental transformation occurs, in such conditions stop the usage of these products.
The potency of the Naivex & Tafero EM should not be evaluated in the pediatric patients with the body weight of less than 25kg.
Tafero EM container should be store at below 30℃, protect from moisture, light and heat. Naivex container should be stored at 25℃, keep the container away from light, moisture & heat.
For Naivex :
Naivex combines with drugs excreted through OCT2 or MATE1 (dofetilide or metformin), causes elevation of plasma concentration of these drugs.
Dolutegravir is a substrate of UGT1A3, UGT1A9, BCRP & P-gp transporters.
Naivex combined with the drug which prohibits these enzymes or transporters cause, increasing the plasma concentration of Dolutegravir.
Naivex combined with etravirine causes decrease in plasma concentration of Dolutegravir.
Naivex tablets is concomitant use with non-nucleoside reverse transcriptase inhibitors; causing depletion of effect of concentration of Naivex.
If Naivex tablets is combines with protease inhibitor causes decreasing in plasma concentration of Dolutegravir.
Naivex concurrently used with anti-mycobacterials, anti-convulsants or herbal products causes depletion in plasma concentration of Dolutegravir
For Tafero EM : Tafero EM is combined with drugs inhibiting BCRP or P-gp transporters, leads to cause alteration in absorption in TAF, results in loss of therapeutic activity of Tafero EM tablet. Tafero EM is majorly eliminated through renally, drug which affect the renal function combined with Tafero EM tablet causes increasing the concentration of TAF and Emtricitabine leads to elevate adverse effects Avoid concomitant use of Tafero EM with tipranavir leads to cause decreasing the effect of concentration of TAF. With anti-convulsants, anti-mycobacterials, herbal products like st. Johns wort causes decreasing the plasma concentration of TAF leads to lowering the effectiveness of Tafero EM tablet.
No contraindication occurs in Tafero EM therapy, but in Naivex causes some anaphylactic reaction to the patients who are contraindicated to the component of Naivex tablet.
DRAWBACK OF Tafero EM
Tafero EM isn't demonstrated for use as pre-introduction prophylaxis (PrEP) to diminish the danger of sexually procured HIV-1 in grown-ups at high hazard.
Dosage adjustment is not recommended for both severe renal & hepatic impaired patients.
Naivex, Tafero EM are anti-retroviral medicines, if missed dose occurred during the course of therapy, must be consult with medical practitioner and follow the instruction as per their advice. On the other way, the missed dose should be avoided and follow the regular schedule.
There is no special antidote is preferred for over dosage of Naivex, because Dolutegravir is highly bound to human plasma protein. In Tafero EM, TAF is eliminated through hemodialysis with an extraction rate of 54%. Emtricitabine is removed by hemodialysis by 30%.
The adverse effects occur in this therapy; Anaphylactic reactions, Immune reconstitution syndrome, Liver toxicity, The most common side effects like; Insomnia, Depression, Abnormal dreams, Dizziness, Headache, nausea, diarrhea, Rash, Fatigue, Vertigo, Gastrointestinal disorders, Hepatitis, Myositis, Some psychiatric problems, Renal impairment, Pruritus, Elevation of AST & ALT, Increasing bilirubin, Creatine kinase elevation, Increase in lipase, Neutrophils elevation, Anxiety.
For TAF, Emtricitabine : Acute aggravation of hepatitis B, Lactic acidosis, Worsening of hepatomegaly with steatosis, Immune restructured syndrome, Renal impairment .