Drug profile of Instgra 50mg Emcure
Instgra 50mg tablets are an anti-retro viral medicine, which containing an anti-retroviral agent known as Dolutegravir.
Dolutegravir 50mg is a termed as DTG used in HIV-1 infection, classified as an integrase inhibitor.
Dolutegravir is generally used in combination with other anti-retroviral drugs for improved results.
Instgra tablets are used for reducing the progression of infection to AIDS, but not for curing the infections.
Dolutegravir binds to infected cells, block the integration process and prevents the further formation of cells.
Instgra is pharmacologically categorized as;
Human immuno deficiency virus integrase strand transfer inhibitor.
Instgra tablets are prescription medicine, used only in HIV infected patients with proper prescription under the knowledge of medical practitioner.
Brand name: Instgra 50mg
Active ingredient: Dolutegravir
Pack: 30 tablets in a container
Category: Anti-retroviral drug
Prescribing information of Instgra
Instgra tablets are primarily used for treating HIV-1 infection in both adults and pediatric patients with the age of 12 years or older with weight of at least 40kg.
Before starting the treatment;
Integrase strand transfer inhibitor (INSTI)-resistance Q148 substitution plus 2 or more additional INSTI-resistance substitutions impoverished virological response is detected while treating with Dolutegravir 50mg as two times a day.
Mechanism of Instgra
Dolutegravir is a HIV-1 antiviral operator. It restrains HIV integrase by authoritative to the dynamic site and obstructing the strand exchange venture of retroviral DNA incorporation in the host cell. The strand exchange step is fundamental in the HIV replication cycle and results in the restraint of viral movement.
After single dose administration of Instgra causes,
AUC: 53.6mcg/ml; Cmax: 3.67 mcg/ml & Cmin: 1.11mcg/ml
Maximum plasma concentration of Dolutegravir is between 2 to 3 hours
The steady state of Dolutegravir is reaches within almost 5 days.
The apparent volume of distribution is 17.4L
Dolutegravir is broadly binds to human plasma protein by 98.9% of uptake dose.
The metabolism of Dolutegravir is occurs largely in liver.
The metabolites formed during the metabolism has very short life period.
There are three major metabolic pathways such as;
1st pathway: Glucuronidation by UGT1A1
2nd pathway: Occurs by Carbon oxidation by CYP3A4
3rd pathway: Oxidative defluorination & glutathione conjugation
The uptake doses are eliminated after metabolism is;
53% in feces as an unchanged form
31% in urine
The terminal half life period of Dolutegravir is 14 hours
The clearance rate of Dolutegravir is 1.0L/hr.
When to take of Instgra
Instgra tablet should be administered with or without food.
Tablets should not be broke, crush, or chew.
Dosage regimens of Instgra
For newly commenced or therapy experienced INSTI patients:
The prescribed dose of Instgra is 50mg should be administered as a single dose
Co administration of strong UGT1A or CYP3A inducers like efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifampin in newly commenced or therapy experienced INSTI;
The prescribed dose is 50mg of Instgra tablet should be administered as a two times aday.
For INSTI already received with certain INSTI related resistance substitutions;
The prescribed dose is 50mg of Instgra should be administered as a two times a day.
The potency of Instgra doses above 50mg as twice daily has not been evaluated.
For 12 years or older/ weighing at least 40kg:
For new patients or already treated INSTI:
The prescribed dose is 50mg of Instgra should be administered as a single dose.
In combination of efavirenz, fosamprenavir/ritonavir, tipranavir/ritonavir, or rifampin; the suggested dose is 50mg of Instgra tablet should be taken as twice dialy.
The potency of Instgra has not been established in pediatric patients with age below 12 years or weighing less than 40kg.
Instgra caused side effects
Common severe adverse effects;
Elevation of hepatic enzymes
Redistribution of fat
Immune reconstitution syndrome
Most common Side effects;
Elevation of AST, AST
Increased creatine kinase
Increased blood glucose
Acute liver failure
Drug- drug interaction
1. Dolutegravir prohibits the renal organic cation transporter, OCT2 in-vitro.
2. Dolutegravir prohibits tubular secretion of creatinine by obstructing OCT2 in-vivo.
3. Co administration of dofetilide or metformin (drugs excreted through OCT2), causes increasing plasma concentration of these drugs.
4. Instgra combined with drugs which induces UGT1A3, UGT1A9, BCRP & P-gp enzymes & transporters may leads to deplete the Instgra plasma concentration.
5. Concurrent use of Instgra with drugs which inhibits these above meioned enzymes, causes increasing concentration of Dolutegravir.
6. Dolutegravir plasma concentration may reduced by etravirine.
7. Instgra with nevirapine causes decreasing the effect of concentration of Dolutegravir.
8. Instgra tablets co administered with protease inhibitors like fosamprenavir/ritonavir, tipranavir/ritonavir; causes decreasing the effect of concentration of Dolutegravir.
9. Instgra with anti-convulsants may causes decreasing effect of consternation of Dolutegravir.
10. Co administration of Instgra tablets with medicines containing polyvalent cations should be avoided, because of decreasing the effect of concentration of these cations.
11. Rifampin concurrently used with Instgra tablets, leads to cause depleting the effect of concentration of Dolutegravir.
Food drug interaction
Dolutegravir should not be concurrently taken with mineral or vitamin containing substances, it may lead to increase the ion content, and this alteration intercedes with absorption of Dolutegravir and depletes the effectiveness.
A minor food drug interaction occurs.
Diet should be maintained only after getting advice from the medical adviser.
Grape fruit or juice
Vitamin E, C containing foods
Hypersensitivity reactions may occur due to patients may contraindicate to the component present in the Instgra tablets.
Concurrent use of Instgra with dofetilide or metformin should be contraindicated, because this combination may leads to increase the dofetilide or metformin plasma concentration and causes life threatening events.
Anaphylactic reactions: If patient may contraindicated to the component of Instgra, should be withdraw the treatment.
Severity of infection should be monitored.
Provide with general supportive measures.
Hepatitis B or C co infected patients: There is a risk of elevation of serum transaminase in case of treating with Dolutegravir.
The levels of transaminase were reliable with resistant reconstitution disorder or hepatitis B reactivation especially in the setting where against hepatitis treatment was pulled back.
Proper lab test should be proceeding before starting treatment and checking for hepatotoxicity amid treatment with Dolutegravir are prescribed in patients with fundamental hepatic sickness, for example, hepatitis B or C.
Redistribution of fat: Obesity is the major risk factor occurred due to accumulation of fat on body tissues.
In this condition, treatment should be discontinued.
Immune reconstitution syndrome: Stop the treatment
Pregnancy and lactation
Pregnancy category B
Instgra tablets should be used very cautiously in pregnancy condition only after knowing the risk benefits associated with fetal.
Breast feeding should not be allowed for preventing the spreading of infections.
Storage and handling
Instgra tablet container should be stored at 25oC
Protect from light, heat, & moisture.
Instgra tablets are anti-retroviral medicine, in case of missed dose condition patient must be consult with physician and follow the instructions.
Maintain the regular dosing schedule.
The missed dose is also one of the reasons for over dosage condition.
If over dosage occurs, patient must be;
Provide with supportive treatments
Monitor the manifestation related to over dosage of Instgra.
Dialysis is not applicable, because it has high binding property.