Brand name : Trustiva
Active substances : Efavirenz + Emtricitabine + Tenofovir disoproxil fumarate
Strength : 600mg + 200mg + 300mg respectively
Manufactured by : Hetero drugs Ltd
Pack : 30 tablets in a container
Category : Anti-retroviral drug
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.
Trustiva tablets should be taken on an empty stomach at bed time. 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.
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. Tenofovir elimination: glomerular filteration & tubular secretion. The mean half life period of efavirenz is 52 to 76 hours Elimination: urine by 14 to 34%; feces by 16 to 61%.
Efavirenz shows hostile to retroviral movement by repressing the turn around transcriptase chemical which is basic viral RNA coordinated DNA polymerase protein. The arrangement of dynamic triphosphorylated frame is vital for the impact of efavirenz, variety happens intracellularly. In light of the cell compose show in the body is required for phosphorylation. The meddling of age of DNA duplicates of viral RNA is happened by restraining the chemical RT. This new DNA duplicates is required for new popular creation. This is closed as restraint of cell division.
Emtricitabine is changed over into dynamic frame known as Emtricitabine 5' triphosphate which is basic for hindrance of viral multiplication. This metabolite battles with deoxycytidine 5' triphosphate, is a characteristic substrate and get converged into viral DNA which prompts chain disposal.
Tenofovir DF :
This is like Emtricitabine, tenofovir is battling with substrate called deoxyadenosine 5' triphosphate and converged into DNA of infection which may closed as restriction of RT action. At long last popular increase gets influenced. NRT is a catalyst required for virion get together, tenofovir DF causes hindrance of viral fasten stretching and to create youthful demolition of DNA translation, prompts block the viral augmentation. Tenofovir DF is a chain eliminator.
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.
Anaphylactic reactions may produce due to patients may contraindicate to the component present in the Trustiva tablets. Trustiva is contraindicated to some drugs like; Voriconazole 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.
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. .
Safety precautions should be taken in the patients who are suspected with; Patients co infected with HIV-1 HBV Drug interactions 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
The most common adverse effects :
Severe acute aggravation of hepatitis B, Lactic acidosis & hepatomegaly with steatosis, Nervous disorders, Newly commenced or worsening of renal impairment, Rash, Liver injury, Bone defects, Immune reconstitution syndrome, Redistribution of fat.
Common side effects :
Diarrhea, Nausea, Vomiting, Fatigue, Infections & infestations, Sinusitis, Respiratory tract infections, Nasopharyngitis, Headache, Dizziness, Anxiety, Depression, Insomnia, Rash.
Lab abnormality :
Increased levels of; Cholesterol, Creatine kinase, Serum amylase, Alkaline phosphatase,, AST, ALT, Blood glucose, Glycosuria, Neutropenia, Triglycerides. Post marketing reports: Palpitations, Tinnitus , Vertigo, Gynecomastia, Abnormal vision, Constipation, Malabsorption, Asthenia, Hepatobiliary disorders, Allergy, Pancreatitis.