Drug profile of Trustiva
Trustiva tablets are containing active constituents which are having anti-retroviral activity drugs known as Tenofovir disoproxil fumarate, Efavirenz, Emtricitabine.
Trustiva is a FDA approved product, which is active against HIV 1 infection condition.
Trustiva containing components are;
Efavirenz: Non nucleoside reverse transcriptase inhibitor
Emtricitabine: Nucleoside reverse transcriptase inhibitors
Tenofovir DF: Nucleoside reverse transcriptase inhibitors.
All these drugs are involved in inhibiting reverse transcriptase enzyme which is essential for viral multiplication.
Trustiva tablets are not considered as curable medicine, but it will diminish the amount of HIV in the body and prevent the further progression into AIDS.
Brand name: Trustiva
Active substances: Efavirenz + Emtricitabine + Tenofovir disoproxil fumarate
Strength: 600mg + 200mg + 300mg respectively
Pack: 30 tablets in a container
Category: Anti-retroviral drug
Prescribing information of Trustiva
The common prescribing information of Trustiva tablets is used to treat HIV-1 infection by used alone or by combining with other anti-retroviral drugs.
A Trustiva use is applicable for adults & pediatric patients about 12 years of age and older.
Mechanism of Trustiva
Efavirenz exhibits anti-retroviral activity by inhibiting the reverse transcriptase enzyme which is essential viral RNA directed DNA polymerase enzyme.
The formation of active triphosphorylated form is necessary for the effect of efavirenz, variation occurs intracellularly.
Based on the cell type present in the body is required for phosphorylation.
The interfering of generation of DNA copies of viral RNA is occurred by inhibiting the enzyme RT.
This new DNA copies is required for new viral production.
This is concluded as inhibition of cell division.
Emtricitabine is converted into active form known as Emtricitabine 5’ triphosphate which is essential for inhibition of viral proliferation. This metabolite fights with deoxycytidine 5’ triphosphate, is a natural substrate and get merged into viral DNA which leads to chain elimination.
This is similar to Emtricitabine, tenofovir is struggling with substrate called deoxyadenosine 5’ triphosphate and merged into DNA of virus which may concluded as prohibition of RT activity.
Finally viral multiplication gets affected.
NRT is an enzyme required for virion assembly, tenofovir DF causes inhibition of viral chain elongation and to produce immature destruction of DNA transcription, leads to obstruct the viral multiplication.
Tenofovir DF is a chain eliminator.
Efavirenz plasma concentration time is 3 to 5 hours
Steady state of efavirenz is reached between 6 to 10days.
Emtricitabine plasma concentration time reaches within one hour.
Tenofovir bioavailability occurs by 25%
Maximum plasma concentration is 1.0 ± 0.4 hours.
Volume of distribution of tenofovir is 1.3 ± 0.6L/kg.
Tenofovir has low plasma protein binding capacity with the range of 0.7 to 7.2%
Emtricitabine is highly bound to plasma protein by 80%.
Blood plasma ratio of Emtricitabine is 1.0
Human plasma protein binding capacity of efavirenz is by 99.5 to 99.7%.
The metabolism of efavirenz is involved by CYP3A & CYP2B6 isoenzymes.
The efavirenz metabolite is induced majorly by cytochrome isoenzymes to hydrolyzed metabolites.
The metabolism of tenofovir is not mediated by cytochrome enzymes.
The metabolism process of Emtricitabine is not so clear.
Nearly 70% of Emtricitabine is occurred in urine, 13.7% in feces.
The terminal half life period of Emtricitabine is 10 hours.
The dose of tenofovir nearly 32% should be recovered in urine which is in unchanged form.
The terminal half life period of tenofovir is 17 hours.
The elimination of tenofovir is majorly occurs through glomerular filteration & tubular secretion.
The mean half life period of efavirenz is 52 to 76 hours
Elimination occurs via urine at 14 to 34%; feces at 16 to 61%.
When to take the Trustiva
Trustiva tablets should be taken on an empty stomach at bed time.
Dosage regimens of Trustiva
The recommended dose of Trustiva for both adults & pediatric patients with 12 years of age or older, one tablet should be taken as a single dose.
In renal impairment:
Trustiva is a fixed dose combination tablet, if patient may require dosage adjustment should not recommended in moderate or severe conditions with the creatinine clearance below 50ml/min.
Rifampin concomitant use:
Patients with weigh of 50kg or more, Trustiva should be combined with rifampin, by increasing dose of efavirenz 200mg/day.
Trustiva caused side effects
The most common adverse effects;
Severe acute aggravation of hepatitis B
Lactic acidosis & hepatomegaly with steatosis
Newly commenced or worsening of renal impairment
Immune reconstitution syndrome
Redistribution of fat
Common side effects;
Infections & infestations
Respiratory tract infections
Increased levels of;
Post marketing reports:
Drug- drug interaction
The substrate of CYP3A or CYP2B6 combined with Trustiva, causes decreasing plasma concentration of these substrates.
Trustiva with CYP3A inducers causes increasing clearance of efavirenz leads to decreasing the plasma concentrations.
Co administration of Trustiva with drugs which reduce the renal functions may leads to increase the plasma concentration of Emtricitabine & tenofovir DF leads to increase the adverse effects.
Trustiva tablets combined with atazanavir & other protease inhibitors, causes decreasing the effect of concentration of atazanavir and increasing the tenofovir concentration.
Trustiva with Didanosine causes increasing effect of concentration of Didanosine
Trustiva with other NNRTI leads to cause increasing or decreasing the effect of concentration of efavirenz.
Trustiva with anti-coagulant, anti-convulsants, anti-depressants, or anti-fungals leads to cause decreasing the effect of concentration of these following drugs.
Trustiva combined with any anti-infective, anti-mycobacterials, anti-malarial or calcium channel blocker causes decreasing the effect of concentration of these drugs.
Trustiva with lipid lowering drugs, hormonal contraceptives or immuno suppressants, causes decreasing effect of concentration of these drugs.
Food drug interaction
Trustiva tablets are administered on an empty stomach, at bedtime because of decreasing neurological problems.
Anaphylactic reactions may produce due to patients may contraindicate to the component present in the Trustiva tablets.
Trustiva is contraindicated to some drugs like;
The co administration of Trustiva with voriconazole, efavirenz one of the active component present in Trustiva causes depletion of plasma concentration of voriconazole which may leads to loss of therapeutic effects.
Safety precautions should be taken in the patients who are suspected with;
Patients co infected with HIV-1 HBV
Lactic acidosis or hepatomegaly with steatosis: Stop the treatment
Co administration of some drugs: Some concomitant use of drugs should be cause adverse effects.
QT prolongation: monitor ECG periodically and patients may treat with alternative medications.
Psychiatric symptoms: risk factors should be frequently and provided with supportive measures
Nervous symptoms: To reduce the symptoms, Trustiva should be taken at bed time
Renal impairment: In severe condition, discontinue the treatment.
Reproductive risk: Trustiva is contraindicated to pregnancy condition. Avoid becoming pregnant
Rash: Alternative treatment should be provided
Liver toxicity: Liver function test should be taken periodically
Bone defects: Vitamin D supplements should be given to the patients, monitor the bone mineral density.
Convulsions: Provide with anti-convulsants medication and monitor the risk of seizures.
Immune reconstitution syndrome: Discontinue the therapy
Redistribution of fat: Discontinue the treatment. The major risk of fat redistribution is obesity
Pregnancy and lactation
Pregnancy category D
Trustiva should not be used in pregnancy and lactating period.
Storage and handling
Trustiva tablet container should be stored at 25oC (77oF)
Protect the container from moisture, heat & light
Missed dose of Trustiva should be avoided.
In case of missed dose of Trustiva, must be consult with medical practitioner and follow the instructions.
Regular dosing schedule of Trustiva tablet should be maintained.
The over dosage of Trustiva tablets are occurred due to missed dose.
The over dosage of efavirenz is caused nervous system symptoms.
Nearly 3 hours of dialysis process, eliminates 30% of Emtricitabine dose from the body within 1.5 hours of dosing time.
Tenofovir is easily removed with the range of 54% by undergoing dialysis.
On 4 hours dialysis process, nearly 10% of dose should be removed from the body.