Emtricitabine and Tenofovir disoproxil fumarate are HIV-1. (human immunodeficiency virus) nucleoside analog reverse transcriptase inhibitors (NRTIs) and Efavirenz is an HIV-1 non-nucleoside analog reverse transcriptase inhibitor (NNRTI).ODITEC can be used alone as a complete regimen, or in combination with other anti-HIV-1 medicines to treat people with HIV-1 infection.

HIV infection destroys CD4+ T cells, which are important to the immune system. The immune system helps fight infection. After a large number of T cells are destroyed, acquired immune deficiency syndrome (AIDS) develops. ODITEC helps block HIV-1 reverse transcriptase, a viral chemical in your body (enzyme) that is needed for HIV-1 to multiply. ODITEC lowers the amount of HIV-1 in the blood (viral load). ODITEC may also help to increase the number of T cells (CD4+ cells), allowing your immune system to improve. Lowering the amount of HIV-1 in the blood lowers the chance of death or infections that happen when your immune system is weak (opportunistic infections).

Oditec is indicated for use alone as a complete regimen or in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults and pediatric patients 12 years of age and older.

The dose of Oditec is one tablet once daily taken orally on an empty stomach. Dosing at bedtime may improve the tolerability of nervous system symptoms. ODITEC has not been studied in adults over 65 years of age.

Rifampin coadministration: When Oditec is administered with rifampin to patients weighing 50 kg or more, an additional 200 mg/day of efavirenz is recommended.

Oditec is contraindicated in patients with previously demonstrated clinically significant hypersepsitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to efavirenz, a component of Oditec.

Oditec is not approved for the treatment of chronic HBV infection, and the safety and efficacy of Oditec have not been established In patients confected with HBV and HIV-1. Severe acute exacerbations of hepatitis B have been reported In patients who are coinfected with HBV and HIV-1 and have discontinued emtricitabine or tenofovir DF, two of the components of Oditec. In some patients infected with HBV and treated with emtricitabine, the exacerbations of hepatitis B were associated with liver decompensation and liver failure.

Treatment with Oditec should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).

QTc prolongation has been observed with the use of efavirenz. Consider alternatives to Oditec when coadministered with a drug with a known risk of Torsade de Pointes or when administered to patients at higher risk of Torsade de Pointes.

Patients with serious psychiatric adverse experiences should seek immediate medical evaluation to assess the possibility that the symptoms may be related to the use of efavirenz, and if so, to determine whether the risks of continued therapy outweigh the benefits.

Patients receiving Oditec should be alerted to the potential for additive central nervous system effects when Oditec is used concomitantly with alcohol or psychoactive drugs. Patients who experience central nervous system symptoms such as dizziness, impaired concentration, and/or drowsiness should avoid potentially hazardous tasks such as driving or operating machinery.

Emtricitabine and tenofovir are principally eliminated by the kidney; however, efavirenz is not. Since Oditec Is a combination product and the dose of the individual components cannot be altered, patients with estimated creatinine clearance below 50 mL/min should not take Oditec.

Oditec should be avoided with concurrent or recent use of a nephrotoxic agent (e.g., high-dose or multiple non-steroidal anti-inflammatory drugs. Persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness may be manifestations of proximal renal tubulopathy and should prompt an evaluation of renal function in at-risk patients.

Efavirenz may cause fetal harm when administered during the first trimester to a pregnant woman. Pregnancy should be avoided in women receiving Oditec

Prophylaxis with appropriate antihistamines before initiating therapy with ODITEC in pediatric patients should be considered. Discontinue if severe rash develops. Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash.

Monitoring of liver enzymes before and during treatment is recommended for patients with underlying hepatic disease, including hepatitis B or C infection; patients with marked transaminase elevations; and patients treated with other medications associated with liver toxicity.

If bone abnormalities are suspected, then appropriate consultation should be obtained.

Cases of osteomalacia associated with proximal renal tubulopathy, manifested as bone pain or pain in extremities and which may contribute to fractures, have been reported in association with the use of tenofovir DF.

Convulsions have been observed in adult and pediatric patients receiving efavirenz, generally in the presence of known medical history of seizures. Caution must be taken in any patient with a history of seizures. Patients who are receiving concomitant anticonvulsant medications primarily metabolized by the liver, such as phenytoin and phenobarbital, may require periodic monitoring of plasma levels

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including the components of Oditec. Autoimmune disorders (such as Graves’ disease, polymyositis, and Guillain-Barré syndrome) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment.

Redistribution/accumulation of body fat, including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting. breast enlargement, and “cushingoid appearance,” has been observed in patients receiving antiretroviral therapy, including efavirenz.

Cardiac Disorders – Palpitations

Ear and Labyrinth Disorders– Tinnitus, vertigo

Endocrine Disorders– Gynecomastia

Eye Disorders -Abnormal vision

Gastrointestinal Disorders – Constipation, malabsorption

Conditions – Asthenia

Hepatobiliary Disorders – Hepatic enzyme increase, hepatic failure, hepatitis.

Immune System Disorders – Allergic reactions

Metabolism and Nutrition Disorders – Redistribution/ accumulation of body fat, hypercholesterolemia, hypertriglyceridemia

Musculoskeletal and Connective Tissue Disorders-Arthralgia, myalgia, myopathy

Abnormal coordination, ataxia, cerebellar coordination and balance disturbances, convulsions, hypoesthesia, paresthesia, neuropathy, tremor

Psychlatric Disorders – Aggressive reactions, agitation, delusions, emotional lability, mania, neurosis, paranoia, psychosis, suicide, catatonia

Respiratory, Thoracic and Mediastinal Disorders – Dyspnea

Skin and Subcutaneous Tissue Disorders 

Flushing, erythema multiforme, photoallergic dermatitis, Stevens-Johnson syndrome

Emtricitabine: No postmarketing adverse reactions have been identified.

Immune System Disorders- Allergic reaction, including angioedema

Metabolism and Nutrition Disorders- Lactic acidosis, hypokalemia, hypophosphatemia

Respiratory, Thoracic, and Mediastinal Disorders- Dyspnea

Gastrointestinal Disorders- Pancreatitis, increased amylase, abdominal pain

Hepatobiliary Disorders- Hepatic steatosis, hepatitis, increased liver enzymes (most commonly AST, ALT, gamma GT)

 

Skin and Subcutaneous Tissue Disorders- Rash

Musculoskeletal and Connective Tissue Disorders – Rhabdomyolysis, osteomalacia (manifested as bone pain and which may contribute to fractures, muscular weakness, myopathy

Renal and Urinary Disorders – Acute renal failure, renal failure, acute tubular necrosis, Fanconi syndrome, proximal renal tubulopathy, interstitial nephritis (including acute cases), nephrogenic diabetes insipidus, renal insufficiency, increased creatinine, proteinuria, polyuria

The following adverse reactions, listed under the body system headings above, may occur as a consequence of proximal renal tubulopathy: rhabdomyolysis, osteomalacia hypokalemia, muscular weakness, myopathy, hypophosphatemia.

Oditec should not be used with lamivudine, zidovudine, abacavir sulfate, rilpivirine, elvitegravir, cobicistat, alafenamide. Voriconazole, defovir dipivoxil, saquinavir, clarithromycin, posaconazole, itraconazole, boceprevir, simeprevir, velpatasvir to be replaced with another medicine when taken with Oditec.

Calcium channel blockers such as diltiazem, verapamil, indinavir, maraviroc, immunosuppressant medicines such as cyclosporine tacrolimus, sirolimus Methadone, rifabutin, Rifampin, cholesterol-lowering medicines such as atorvastatin, pravastatin sodium and sivastatin or the anti-depressant medications bupropion or sertraline dose changes may be needed when these drugs are taken with Oditec.

Tenofovir disoproxil fumarate may increase the amount of didanosine in your blood, which could result in more side effects. So, need to be monitored more carefully if you are taking Oditec and didanosine together. Also, the dose of didanosine may need to be changed.

Atazanavir sulfate, darunavir with ritonavir, lopinavir/ ritonavir, sofosbuvir/ velpatasvir or ledipasvir/sofosbuvir these medicines may increase the amount of tenofovir DF (a component of Oditec) in your blood, which could result in more side effects. sofosbuvir/velpatasvir and Atazanavir sulfate are not recommended with Oditec. Need to be monitored more carefully if you are taking Oditec, darunavir and ritonavir together, or if you are taking Oditec and lopinavir/ritonavir together. The dose of lopinavir/ritonavir should be increased when taken with efavirenz.

Medicine for seizures such as phenytoin, carbamazepine and phenobarbital may want to switch to another medicine or check drug levels in blood from time to time.

Pregnancy should be avoided in women receiving Oditec. Women of childbearing potential should undergo pregnancy testing before initiation of Oditec

Barrier contraception should always be used in combination with other methods of contraception while on therapy with Olitec, Because of the long half-life of efavirenz, use of adequate contraceptive measures for 12 weeks after discontinuation of Oditec is recommended.

Efavirenz: As neural tube defects occur within the first 4 weeks of foetal development (at which time neural tubes are sealed), this potential risk would concern women exposed to efavirenz during the first trimester of pregnancy.

Malformations have been observed in foetuses from efavirenz-treated monkeys 

Emtricitabine and tenofovir disoproxil fumarate:

A moderate amount of data on pregnant women (between 300-1,000 pregnancy outcomes) indicates no malformations or foetal/neonatal toxicity associated with emtricitabine and tenofovir disoproxil fumarate. Animal studies on emtricitabine and tenofovir disoproxil fumarate do not indicate reproductive toxicity.

Oditec should not be used during pregnancy unless the clinical condition of the woman requires treatment with efavirenz/emtricitabine/ tenofovir disoproxil fumarate.

Oditec should not be used during breast-feeding. As a general rule, it is recommended that HIV infected women do not breast-feed their infants in order to avoid transmission of HIV to the infant.

No human data on the effect of Oditec are available

Some patients accidentally taking 600 mg efavirenz twice daily have reported increased nervous system symptoms. One patient experienced involuntary muscle contractions.

If overdose occurs, the patient must be monitored for evidence of toxicity, and standard supportive treatment applied as necessary.

Administration of activated charcoal may be used to aid removal of unabsorbed efavirenz. There Is no specific antidote for overdose with efavirenz. Since efavirenz is highly protein bound, dialysis is unlikely to remove significant quantities of it from blood. Up to 30% of the emtricitabine dose and approximately • 10% of the tenofovir dose can be removed by haemodialysis. It is not known whether emtricitabine or tenofovir can be removed by peritoneal dialysis.

30 Tablets in a HDPE Container

Store below 30°C. Protect from light and moisture. Keep the container tightly closed after use. Keep out of reach of children.

Myanmar Registration No.: R2309A6152

Manufactured by:

SAI MIRRA INNOPHARM PVT. LTD.,

288 & 299, SIDCO Estate,

Ambattur, Chennai – 600 098, India.

Product of:

Zifam Pinnacle Pty. Ltd.. Sydney, Australia.