Description of Instgra - Tafero-EM - 6 Month Course
Instgra tablets are containing active substance known as Dolutegravir.
Tafero EM tablets are containing active substances known as Tenofovir Alafenamide & Emtricitabine.
Dolutegravir is pharmacologically categorized as HIV integrase strand transfer inhibitor.
Tenofovir Alafenamide is pharmacologically categorized as nucleotide reverse transcriptase inhibitor.
Emtricitabine is pharmacologically categorized as nucleoside analogue reverse transcriptase inhibitor.
Pharmacology of Instgra - Tafero-EM - 6 Month Course
Instgra exhibits its anti-retroviral activity by binding to the active site of integrase enzyme which is used to catalyze the transmission of viral genetic material into human chromosome.
This inhibition process is essential for stopping the integrase into binding to viral DMA & leads to blockade the strand transfer step which is responsible for replication of HIV.
Dolutegravir: HIV-1 replication inhibition.
Tenofovir Alafenamide is converted into an active form known as tenofovir.
Tenofovir is essential for;
Stop the conversion of 5’ to 3’ phosphodiester linkage which is essential for DNA elongation.
Stop the proviral DNA transcription.
Emtricitabine is used in combination with other anti-retroviral agents for better activity.
It is essential for;
Elimination of DNA chain elongation
Pharmacokinetics of Instgra Tafero EM
After oral administration of Instgra Tafero EM tablets, reaches peak plasma concentration time of;
Tenofovir Alafenamide at 1 hour & Emtricitabine at 3 hours
Dolutegravir at 2 to 3 hours
The steady state level of Dolutegravir is occurs almost 5 days.
After absorption completed, tenofovir Alafenamide is binds to human plasma protein by 80% & Emtricitabine by <4%.
Dolutegravir is highly bound to human plasma protein by 98.9%
The apparent volume of distribution of Dolutegravir is 17.4L
The blood to plasma ratio of Emtricitabine is 0.6 & Tenofovir Alafenamide is 1.0.
Tenofovir Alafenamide metabolism is mediated by using enzymes like cathepsin A, CES1 or CYP3A.
The metabolism of Dolutegravir is highly induced by UGT1A1 with lesser extent of CYP3A.
The elimination route of Dolutegravir is occurs by renally, & some dose are excreted via feces as an unchanged form.
Tenofovir Alafenamide excreted via metabolism nearly 80%.
Emtricitabine is excreted via glomerular filteration & active tubular secretion.
Half life period of;
TAF: 0.51 hour
Emtricitabine: 10 hours
Dolutegravir: 14 hours
Indication of Instgra - Tafero-EM - 6 Month Course
Generally Tafero EM tablets are used by combining with other anti-retroviral drugs like Instgra (Dolutegravir).
The major indication of Instgra Tafero EM is involved in the treatment of HIV-1 infection.
Tafero EM is not concomitant with protease inhibitors; it is applicable for the adults & pediatric patients with weight of at least 35kg.
The major demerit of Tafero EM is;
It is not indicated for the condition like pre exposure prophylaxis (PrEP) to diminish the exposure of sexually attained HIV-1 infection in adolescents at greater possibility.
Dose & Dosage's of Instgra - Tafero-EM - 6 Month Course
Before starting the treatment for HIV-1 infections, patients should be checked thoroughly for examining the HBV infection is present or not.
Creatinine clearance, urine glucose, urine protein, & other lab values are investigated before initiate the therapy.
Tafero EM is a two drug fixed dose combination containing 25mg of tenofovir Alafenamide & 200mg of Emtricitabine.
The prescribed dose of Tafero EM is one tablet should be administered orally as once daily by taking with or without food.
Tafero EM tablet should not be indicated in patients with severe renal impairment, with creatinine clearance below 30ml/min.
Tafero EM dosage should be applicable for the patients with CrCl greater or equal to 30ml/min & pediatric patients with weight of at least 25kg.
Instgra tablets should be administered with or without food.
Therapy newly commenced or therapy experienced INSTI new or virologically suppressed in adults replacing to Dolutegravir plus rilpivirine;
The suggested dose of Instgra is 50mg (one tablet) should be administered orally as once daily.
Therapy newly commenced or therapy experienced INSTI new while co administering with UGT1A or CYP3A inducers;
The recommended dose is 50mg of Instgra should be administered orally as two times a day.
INSTI experienced with certain INSTI related resistance substitutions;
The recommended dose is 50mg of Instgra tablet should be administered orally as two times a day.
Depending up on the body weight of patients, the dose of Instgra should be calculated;
30 to less than 40kg: The prescribed dose is 35mg of Instgra (one 25mg + one 10mg Instgra) should be taken orally as once daily.
40 or greater: The prescribed dose is 50mg of Instgra should be administered orally as once daily.
Side Effects of Instgra - Tafero-EM - 6 Month Course
The most common serious condition of Instgra Tafero EM;
Immune reconstitution syndrome
Severe aggravation of HBV infection
New outbreak or worsening of renal impairment
Lactic acidosis or hepatomegaly with steatosis
Common side effects;
Bone mineral density defects
Increased AST & ALT
Increased creatine kinase
Acute liver failure
Contraindication of Instgra - Tafero-EM - 6 Month Course
Some anaphylactic reactions are formed while patients are contraindicated to the component present in the Instgra Tafero EM.
The combination of Instgra with dofetilide is contraindicated.
Drug Interaction of Instgra - Tafero-EM - 6 Month Course
Instgra Tafero EM tablets are combined with P-gp inducers causes depletion of absorption of tenofovir Alafenamide which concludes as depletion of plasma concentration of TAF which may leads to loss of therapeutic activity of Tafero EM.
Instgra Tafero EM tablets are combined with P-gp or BCRP inhibitors causes elevation of absorption & plasma concentration of TAF.
Instgra Tafero EM tablets combined with drugs which affecting the renal functions causes increased concentration of TAF & leads to elevation of adverse effects related to these drugs.
Instgra Tafero EM tablets combined with tipranavir/ritonavir causes decreased effect of concentration of TAF.
Instgra Tafero EM tablets are combined with anti-convulsants or anti-mycobacterials cause decreased effect of concentration of TAF.
Instgra Tafero EM tablets combined with herbal product like st Johns wort causes decreased effect of concentration of TAF.
Instgra tablets co administered with drugs eliminated via OCT2 or MATE1 causes increased effect of concentration of these drugs.
Instgra tablets are combined with drugs metabolized by UGT1A1 causes increased plasma concentration of Dolutegravir & leads to loss of therapeutic activity of Dolutegravir.
Instgra tablets combined with NNRTI causes decreased Dolutegravir effect of concentration.
Instgra tablet co administered with protease inhibitors causes decreased effect of concentration of Dolutegravir.
Instgra with anti-convulsants causes decreased effect of concentration of Dolutegravir.
Instgra with rifampin causes decreased effect of concentration of Dolutegravir.
Precaution of Instgra - Tafero-EM - 6 Month Course
Serious aggravation of HBV infections;
Before begin the therapy, patients should be examined for the occurrence of advanced HBV infection.
This lethal case occurs in patients with HBV/HIV-1 infection.
Prevent the problem by measuring the HBsAg & anti-HBc levels.
Monitor the ECG levels
Initiate the HBV infection related management.
Hepatic function test should be performed.
Immune reconstitution syndrome;
This fatal case is occurs during the therapy of HIV-1 infections.
In severe condition, stop the treatment.
New outbreak or aggravation of renal impairment;
Avoid the combination of Instgra Tafero EM with drug reducing the renal functions.
Monitor the renal function test.
Avoid the usage of Instgra Tafero EM in renal impaired patients.
Lactic acidosis or severe hepatomegaly with steatosis;
This fatal case is occurs during the anti-retro viral therapy.
Prevent the problem by monitoring the hepatic function & levels of hepatic enzymes.
In severe condition, therapy should be stopped.
During the treatment, some anaphylactic reactions are formed.
In severe condition therapy should be discontinued.
During the therapy with Instgra Tafero EM, patient should be suffered with liver toxicity.
Prevent the problem by examine the patients hepatic function test frequently.
Maintain the hepatic enzyme level.
Loss of virological responses associated with drug interactions;
In some combination treatment, there is chance of patients getting resistance to the related drugs which leads to loss of therapeutic activity.
Monitor the possible adverse effects associated to these drug combinations.
Usage & Safety profile of Instgra - Tafero-EM - 6 Month Course Pregnancy & Lactation
The pregnancy category of Instgra Tafero EM is;
Dolutegravir is B
Tenofovir Alafenamide is B & Emtricitabine is B
Instgra Tafero EM tablets should be used cautiously during the pregnancy period.
Instgra Tafero EM tablets should be prescribed in pregnancy condition only after knowing the risk benefits associated with these medicines.
It is probably safe to use in lactating period, with caution
Avoid becoming pregnancy during the therapy.
Storage of Instgra - Tafero-EM - 6 Month Course
Tafero EM tablet container should be stored at temperature below 30oC.
Instgra tablets container should be stored at temperature 25oC.
Keep the container away from moisture, heat & light.
The occurrence of missed dose condition should be avoided.
In case of missed dose patients should be consult with medical practitioner & follow the instructions.
Avoid self medication
On the other hand the missed dose should be skipped if possible.