GPO-Vir T

GPO-Vir T

Manufacturer:

GPO

Distributor:

GPO
Full Prescribing Info
Contents
Efavirenz, emtricitabine, tenofovir disoproxil fumarate.
Description
Each tablet contains 600 mg of efavirenz, 200 mg of emtricitabine and 300 mg of tenofovir disoproxil fumarate.
Excipients/Inactive Ingredients: Microcrystalline cellulose, Croscarmellose sodium, Hydroxypropyl cellulose, Sodium lauryl sulphate, Magnesium stearate, Lactose monohydrate, Hydrolyzed polyvinyl alcohol, Hydroxypropyl methylcellulose, Titanium dioxide, Talcum, Iron oxide red and Ferrosoferric oxide.
Action
Pharmacology: Pharmacodynamics: Mechanism of action: Efavirenz: Efavirenz is non-nucleoside reverse transcriptase inhibitor (NNRTI) of human immunodeficiency virus type 1 (HIV-1). Efavirenz activity is mediated predominantly by noncompetitive inhibition of HIV-1 reverse transcriptase. HIV-2 reverse transcriptase and human cellular DNA polymerases alpha, beta, gamma, and delta are not inhibited by efavirenz.
Emtricitabine: Emtricitabine, a synthetic nucleoside analog of cytidine, is phosphorylated by cellular enzymes to form emtricitabine 5'-triphosphate. Emtricitabine 5'-triphosphate inhibits the activity of the HIV-1 reverse transcriptase by competing with the natural substrate deoxycytidine 5'-triphosphate and by being incorporated into nascent viral DNA, which results in chain termination. Emtricitabine 5'-triphosphate is a weak inhibitor of mammalian DNA polymerases alpha, beta, and epsilon and mitochondrial DNA polymerase gamma.
Tenofovir: Tenofovir disoproxil fumarate is an acyclic nucleoside phosphonate diester analog of adenosine monophosphate. Tenofovir disoproxil fumarate requires initial diester hydrolysis for conversion to tenofovir and subsequent phosphorylations by cellular enzymes to form tenofovir diphosphate. Tenofovir diphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with the natural substrate deoxyadenosine 5'-triphosphate and, after incorporation into DNA, by DNA chain termination. Tenofovir diphosphate is a weak inhibitor of mammalian DNA polymerases alpha, beta, and mitochondrial DNA polymerase gamma.
Dose/concentration/time-pharmacodynamic response relationship: Data is not available.
Pharmacokinetics: Absorption: Efavirenz: The absorption of efavirenz is increased by fatty meals. The time to peak is 3-5 hours.
Emtricitabine: Emtricitabine is rapidly and extensively absorbed following oral administration with peak plasma concentrations (Cmax) occurring at 1 to 2 hours postdose. Emtricitabine may be taken with or without food. When administered with food, the area under the plasma-time curve (AUC) of emtricitabine is unaffected while Cmax decreases by 29%.
Tenofovir: Bioavailability of tenofovir is approximately 25% in fasted state or increases approximately 40% with high-fat meal. The time to peak in serum is 36-84 minutes (fasting) or 96-144 minutes (with high-fat meal).
Distribution: Efavirenz: The cerebrospinal fluid concentrations of efavirenz exceed free fraction in serum. More than 99% of efavirenz binds to protein, primarily to albumin.
Emtricitabine: The binding of emtricitabine to human plasma proteins is less than 4%.
Tenofovir: The volume of distribution of tenofovir is 1.2-1.3 L/kg. The protein binding is less than 7% to serum proteins.
Metabolism: Efavirenz: Efavirenz is metabolized in liver via CYP3A4 and 2B6 to inactive hydroxylated metabolites. It may induce its own metabolism.
Emtricitabine: The biotransformation of emtricitabine includes oxidation of the thiol moiety to form the 3'-sulfoxide diastereomers (approximately 9% of the dose) and conjugation with glucuronic acid to form 2'-O-glucuronide (approximately 4% of the dose). No other metabolites are identifiable.
Tenofovir: Tenofovir disoproxil fumarate is converted intracellularly by hydrolysis (by non-CYP enzymes) to tenofovir, then phosphorylated to the active tenofovir diphosphate.
Excretion: Efavirenz: Efavirenz is excreted in feces (16-61% primarily as unchanged drug) and in urine (14-34% as metabolites). The half-life of elimination after single dose is 52-76 hours while that after multiple doses is 40-55 hours.
Emtricitabine: The plasma emtricitabine half-life is approximately 10 hours. The renal clearance of emtricitabine is greater than the estimated creatinine clearance (CrCl), suggesting elimination by glomerular filtration and active tubular secretion. Emtricitabine is mainly excreted in urine (86% primarily as unchanged drug and 13% as metabolites) and in feces (14%).
Tenofovir: Tenofovir is mainly excreted in urine (70-80%) via filtration and active secretion, primarily as unchanged tenofovir. The half-life of elimination is approximately 17 hours.
Toxicology: Mechanism of toxicity: Data is not available.
Indications/Uses
GPO-VIR T 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.
Dosage/Direction for Use
Adults and pediatric patients 12 years of age and older with at least 40 kg: HIV infection: Usual dosage: 1 tablet once daily taken on an empty stomach. Dosing at bedtime may improve the tolerability of nervous system symptoms.
Concomitant therapy: When administered with rifampin to patients weighing 50 kg or more, an additional 200 mg/day of efavirenz is recommended.
Renal function impairment: Because this is a fixed-dose combination, it should not be prescribed for patients requiring dosage adjustment, such as those with moderate or severe renal impairment (creatinine clearance [CrCl] less than 50 mL/min). Routine monitoring of CrCl, serum phosphorus, urine glucose, and urine protein should be performed in patients with mild renal impairment.
Hepatic function impairment: Mild hepatic impairment: May treat at the approved dose. Use with caution.
Moderate or severe hepatic impairment: Not recommended.
Mode of administration: Take this tablet on an empty stomach.
Overdosage
Efavirenz: Manifestation: Limited information is available on acute toxicity of efavirenz. Increased adverse CNS effects, including involuntary muscle contractions, have been reported in some patients inadvertently took efavirenz in a dosage of 600 mg twice daily instead of the usually recommended adult dosage of 600 mg once daily.
Treatment: If acute overdosage of efavirenz occurs, supportive and symptomatic treatment should be initiated and the patient observed closely. Activated charcoal may be administered to prevent absorption of drug. There is no known antidote for efavirenz overdosage. Hemodialysis or peritoneal dialysis is unlikely to remove substantial amounts of efavirenz from the body, and these procedures should not be relied on to enhance elimination of the drug.
Emtricitabine: There is no known antidote for emtricitabine. If overdose occurs, monitor the patient for signs of toxicity and apply standard supportive treatment as necessary.
Hemodialysis treatment removes approximately 30% of the emtricitabine dose over a 3-hour dialysis period, starting within 1.5 hours of emtricitabine dosing (blood flow rate of 400 mL/min and a dialysate flow rate of 600 mL/min). It is not known whether emtricitabine can be removed by peritoneal dialysis.
Tenofovir: If overdose occurs, monitor the patient for evidence of toxicity and apply standard supportive treatment as necessary.
Tenofovir is efficiently removed by hemodialysis with an extraction coefficient of approximately 54%. Following a single dose of tenofovir 300 mg, a 4-hour hemodialysis session removed approximately 10% of the administered tenofovir dose.
Contraindications
It is contraindicated to patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions) to efavirenz. The coadministration with voriconazole is also contraindicated.
Warnings
Warning (based on the Ministry of Public Health Announcement): The drug may cause severe hepatotoxicity.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate in combination with other antiretrovirals.
Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate is not approved for the treatment of chronic hepatitis B virus (HBV) infection, and the safety and efficacy have not been established in patients coinfected with HBV and HIV-1. Severe, acute exacerbations of hepatitis B have been reported in patients who have discontinued emtricitabine or tenofovir disoproxil fumarate. Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who discontinue therapy and are coinfected with HIV-1 and HBV. If appropriate, initiation of anti-hepatitis B therapy may be warranted.
Special Precautions
Lactic acidosis and severe hepatomegaly with steotosis: Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs in combination with other antiretrovirals. A majority of these cases have been in women. Obesity and prolonged nucleoside exposure may be risk factors.
Exercise particular caution when administering nucleoside analogs to any patient with known risk factors of liver disease; however, cases have also been reported in patients with no known risk factors. Discontinue treatment with GPO-VIR T 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.
Immune reconstitution syndrome: Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. During the initial phase of combination antiretroviral treatment, patients whose immune systems respond may develop an inflammatory response to indolent or residual opportunistic infections (such as Mycobacterium avium infection, cytomegalovirus, Pneumocystis jiroveci pneumonia (PJP), or tuberculosis) that may necessitate further evaluation and treatment.
Fat redistribution: Redistribution/accumulation of body fat including central obesity, dorsocervical fat enlargement (buffalo hump), peripheral wasting, facial wasting, breast enlargement, and "cushingoid appearance" have been observed in patients receiving antiretroviral therapy.
Decreased bone mineral density: In a 144-week study of treatment-naïve patients receiving tenofovir disoproxil fumarate, decreases in bone mineral density (BMD) were seen at the lumbar spine and hip in both arms of the study. The majority of the reduction in BMD occurred in the first 24 to 48 weeks of the study, and this reduction was sustained through 144 weeks. Tenofovir disoproxil fumarate was associated with significant increases in biochemical markers of bone metabolism (e.g., serum bone-specific alkaline phosphatase, serum osteocalcin, serum C-telopeptide, and urinary N-telopeptide), suggesting increased bone turnover. Serum parathyroid hormone levels and 1.25-vitamin D levels were also higher in patients receiving tenofovir disoproxil fumarate.
Osteomalacia and renal dysfunction: May cause osteomalacia with proximal renal tubulopathy. Bone pain, extremity pain, fractures, arthralgia, weakness, and muscle pain have been reported. In patients at risk for renal dysfunction, evaluate persistent or worsening bone or muscle symptoms for hypophosphatemia and osteomalacia.
Psychiatric symptoms: Serious psychiatric adverse reactions have been reported in patients treated with efavirenz.
The specific serious psychiatric reactions were severe depression, suicidal ideation, nonfatal suicide attempts, aggressive behavior, paranoid reactions and manic reactions. Factors associated with an increase in the occurrence of these psychiatric symptoms are history of injection drug use, psychiatric history, and receipt of psychiatric medication at entry. Instruct patients with serious psychiatric adverse reactions to seek immediate medical evaluation in order 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.
Skin rash: Rash associated with blistering, moist desquamation or ulceration occurred 0.9% in patients treated with efavirenz. The incidence of grade 4 rash (e.g., erythema multiforme, Stevens-Johnson Syndrome) was 0.1%. Discontinue GPO-VIR T in patients developing severe rash associated with blistering, desquamation, mucosal involvement or fever. Appropriate antihistamines and/or corticosteroids may improve the tolerability and hasten the resolution of rash.
Central nervous system (CNS) effects: CNS symptoms including dizziness, insomnia, impaired concentration, somnolence, abnormal dreams and hallucinations are found in patients receiving efavirenz. These symptoms usually begin during the first or second day of therapy and generally resolve after the first 2 to 4 weeks of therapy. Alert patients receiving GPO-VIR T to the potential for additive CNS reactions when used concomitantly with alcohol or psychoactive drugs.
Convulsions: Convulsions have been observed in patients receiving efavirenz, generally in those with a known medical 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. Exercise caution in any patient with a history of seizures.
Hepatic effects: 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. In patients with persistent elevations of serum transaminases to greater than 5 times the upper limit of normal (ULN), weigh the benefits of continued therapy with efavirenz against the unknown risks of significant liver toxicity.
Hepatic function impairment: GPO-VIR T is not recommended for patients with moderate or severe hepatic impairment because there are insufficient data to determine an appropriate dose. Because of the extensive cytochrome P450-mediated metabolism of efavirenz and limited clinical experience in patients with hepatic impairment, caution must be exercised in these patients.
Renal toxicity: May cause renal toxicity (acute renal failure and/or Fanconi syndrome [renal tubular injury with severe hypophosphatemia]); avoid use with concurrent or recent nephrotoxic therapy (including high-dose or multiple nonsteroidal anti-inflammatory drug [NSAID] use).
Effect on ability to drive and use machine: Advise patients who experience CNS symptoms, such as dizziness, drowsiness, and/or impaired concentration to avoid potentially hazardous tasks, such as driving or operating machinery.
Use in Children: Only administer GPO-VIR T to pediatric patients 12 years of age and older with a body weight of at least 40 kg. Because this is a fixed-dose combination tablet, the dose adjustments recommended for pediatric patients younger than 12 years for each individual component cannot be made.
Use In Pregnancy & Lactation
Pregnancy: US Pregnancy category: D.
Based on human data, the drug can cause fetal harm when administered to pregnant women, but the potential benefits from the use of the drug may be acceptable, despite its potential risks.
Efavirenz may cause fetal harm when administered during the first trimester to a pregnant woman. There are no adequate and well-controlled studies in pregnant women. Only use GPO-VIR T during pregnancy if the potential benefit justifies the potential risks to the fetus. If this drug is used during the first trimester of pregnancy or if the patient becomes pregnant while taking this drug, inform the patient of the potential harm to the fetus.
Labor and delivery: Data is not available.
Lactation: The Centers for Disease Control and Prevention recommends that women infected with HIV-1 not breast-feed their infants in order to avoid risking postnatal transmission of HIV-1. Because the risks of low level exposure to emtricitabine and tenofovir to infants are unknown, and because of the potential for HIV-1 transmission, instruct mothers not to breast-feed if they are receiving GPO-VIR T.
Adverse Reactions
The most common adverse reactions include abnormal dreams, depression, diarrhea, dizziness, fatigue, headache, insomnia, nausea, and rash. Other common adverse reactions are anxiety, vomiting, nasopharyngitis, sinusitis, and upper respiratory tract infections.
The other adverse reactions reported at least 5% of patients receiving emtricitabine or tenofovir with other antiretroviral agents are abdominal pain, arthralgia, back pain, dyspepsia, fever, increased cough, myalgia, pain, paresthesia, peripheral neuropathy (including peripheral neuritis, and neuropathy), pneumonia, rash event (including allergic reaction, maculopapular rash, pruritus, pustular rash, rash, urticaria, and vesiculobullous rash) and rhinitis. The other adverse reactions observed in at least 2% of efavirenz-treated patients are abdominal pain, anorexia, dyspepsia, impaired concentration, nervousness, pain, pruritus, and somnolence.
Drug Interactions
Acyclovir, valacyclovir: May decrease the excretion of tenofovir. Monitor therapy.
Adefovir: May diminish the therapeutic effect of tenofovir. Specifically, adefovir-associated mutations in Hepatitis B viral reverse transcriptase may decrease viral susceptibility to tenofovir. Tenofovir may increase the serum concentration of adefovir. Adefovir may increase the serum concentration of tenofovir. Avoid combination.
Afatinib: P-glycoprotein/ABCB1 inducers may decrease the serum concentration of afatinib.
Alcohol (ethyl): Efavirenz may enhance the adverse/toxic effect of alcohol (ethyl). Efavirenz may decrease the serum concentration of alcohol (ethyl). Monitor therapy.
Aminoglycosides: May increase the serum concentration of tenofovir. Tenofovir may increase the serum concentration of aminoglycosides. Monitor therapy.
Aripiprazole: CYP3A4 inducers may decrease the serum concentration of aripiprazole. Consider therapy modification.
Artemether: Efavirenz may decrease the serum concentration of artemether. Concentrations of dihydroartemisinin (active metabolite of artemether) may also be decreased by efavirenz. Monitor therapy.
Atazanavir: Tenofovir and efavirenz may decrease the serum concentration of atazanavir. Atazanavir may increase the serum concentration of tenofovir. Consider therapy modification.
Atorvastatin: Efavirenz may decrease the serum concentration of atorvastatin. Monitor therapy.
Atovaquone: Efavirenz may decrease the serum concentration of atovaquone. Avoid combination.
Axitinib: CYP3A4 inducers (moderate) may decrease the serum concentration of axitinib. Avoid combination.
Azelastine (nasal): CNS depressants may enhance the CNS depressant effect of azelastine (nasal). Avoid combination.
Boceprevir: Efavirenz may decrease the serum concentration of boceprevir. Boceprevir may increase the serum concentration of efavirenz. Avoid combination.
Bosentan: May decrease the serum concentration of CYP3A4 substrates. Monitor therapy.
CYP2C9 inhibitors (moderate) may increase the serum concentration of bosentan.
Concomitant use of both a CYP2C9 inhibitor and a CYP3A4 inhibitor or a single agent that inhibits both enzymes with bosentan is likely to cause a large increase in serum concentrations of bosentan and is not recommended. Monitor therapy.
Bosutinib: CYP3A4 inducers (moderate) may decrease the serum concentration of bosutinib. Avoid combination.
Brentuximab vedotin: P-glycoprotein/ABCB1 inducers may decrease the serum concentration of brentuximab vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component maybe decreased. Monitor therapy.
Brimonidine (topical): May enhance the CNS depressant effect of CNS depressants. Monitor therapy.
Buprenorphine: Efavirenz may decrease serum concentrations of buprenorphine and the active metabolites of buprenorphine. Monitor therapy.
Bupropion: Efavirenz may decrease the serum concentration of bupropion. Monitor for decreased response to bupropion in patients treated with efavirenz. Increased bupropion doses may be required. Avoid the use of naltrexone/bupropion for weight management in patients receiving efavirenz. Monitor therapy.
Calcium channel blockers: Efavirenz may decrease the serum concentration of calcium channel blockers. Monitor therapy.
Canagliflozin: Efavirenz may decrease the serum concentration of canagliflozin. Consider therapy modification.
Cannabis: CYP2C9 inhibitors (moderate) may increase the serum concentration of cannabis. More specifically, tetrahydrocannabinol serum concentrations may be increased. Cannabis may enhance the CNS depressant effect of CNS depressants. Monitor therapy.
Carbamazepine: Reverse transcriptase inhibitor (non-nucleoside) may decrease the serum concentration of carbamazepine. This mechanism applies specifically to efavirenz. Carbamazepine may decrease the serum concentration of reverse transcriptase inhibitors (non-nucleoside). Avoid combination.
Carvedilol: CYP2C9 inhibitors (moderate) may increase the serum concentration of carvedilol. More specifically, concentrations of the S-carvedilol enantiomer may be increased. Monitor therapy.
Caspofungin: Inducers of drug clearance may decrease the serum concentration of caspofungin. Consider therapy modification.
Cidofovir: May decrease the excretion of tenofovir. Monitor therapy.
Citalopram: CYP2C9 inhibitors (moderate) may increase the serum concentration of citalopram. Patients using this combination should be monitored closely for evidence of citalopram toxicity (e.g., serotonin syndrome, QT prolongation etc.). Consider therapy modification.
Clarithromycin: Efavirenz may decrease the serum concentration of clarithromycin. Consider using an alternative antibiotic, such as azithromycin, for patients taking efavirenz. If concomitant therapy cannot be avoided, monitor for decreased therapeutic effect of clarithromycin and increased incidence of skin rash. Consider therapy modification.
Clopidogrel: CYP2C19 inhibitors (moderate) may decrease serum concentrations of the active metabolites of clopidogrel. Monitor patients closely for evidence of a diminished response to clopidogrel. Consider therapy modification.
CNS depressants: May enhance the adverse/toxic effect of other CNS depressants. Monitor therapy.
Cobicistal: May enhance the adverse/toxic effect of tenofovir. Monitor therapy.
Contraceptives (progestins): Efavirenz may decrease the serum concentration of contraceptives (progestins). Use an alternative or additional method of contraception due to possibly decreased contraceptive effectiveness. Injected depot medroxyprogesterone acetate does not appear to participate in this interaction. Consider therapy modification.
Cyclosporine (systemic): Efavirenz may decrease the serum concentration of cyclosporine (systemic). Cyclosporine dose adjustment may be required. Consider therapy modification.
CYP2B6 inducers (strong): May increase the metabolism of CYP2B6 substrates. Consider therapy modification.
CYP2B6 inhibitors (moderate): May decrease the metabolism of CYP2B6 substrates. Monitor therapy.
CYP2C19 substrates: CYP2C19 inhibitors (moderate) may decrease the metabolism of CYP2C19 substrates. Monitor therapy.
CYP2C9 substrates: CYP2C9 inhibitors (moderate) may decrease the metabolism of CYP2C9 substrates. Monitor therapy.
CYP3A4 inducers (moderate): May decrease the serum concentration of CYP3A4 substrates. Monitor therapy.
CYP3A4 inducers (strong): May increase the metabolism of CYP3A4 substrates. Consider therapy modification.
CYP3A4 substrates: CYP3A4 inducers (moderate) may decrease the serum concentration of CYP3A4 substrates. Monitor therapy.
Dabigatran etexilate: P-glycoprotein/ABCB1 inducers may decrease the serum concentration of dabigatran etexilate. Avoid concurrent use of dabigatran with P-glycoprotein inducers when possible. Closely monitor for decreased levels/effects of dabigatran if concomitantly administering p-glycoprotein inducers, particularly strong inducers. Avoid combination.
Dabrafenib: May decrease the serum concentration of CYP3A4 and CYP2B6 substrates. Consider therapy modification.
Darunavir: Efavirenz may decrease the serum concentration of darunavir. Tenofovir may increase the serum concentration of darunavir. Darunavir may increase the serum concentrations of efavirenz and tenofovir. Monitor therapy.
Dasabuvir: Efavirenz may enhance the adverse/toxic effect of dasabuvir. Efavirenz may decrease the serum concentration of dasabuvir. Avoid combination.
Deferasirox: May decrease the serum concentration of CYP3A4 substrates. Monitor therapy.
Diclofenac (systemic): May enhance the adverse/toxic effect of tenofovir. Diclofenac may increase the risk of tenofovir-associated nephrotoxicity and alternatives to that combination should be used whenever possible. Use of any high-dose NSAID or multiple NSAIDs with tenofovir should be avoided. Consider therapy modification.
Didanosine: Tenofovir may diminish the therapeutic effect of didanosine. Tenofovir may increase the serum concentration of didanosine. Avoid concomitant treatment with tenofovir and didanosine.
Diltiazem: Efavirenz may decrease the serum concentration of diltiazem. Monitor therapy.
Dolutegravir: Efavirenz may decrease the serum concentration of dolutegravir. Consider modification.
Doxorubicin (conventional): P-glycoprotein/ABCB1 inducers may decrease the serum concentration of doxorubicin (conventional). Consider therapy modification.
Doxylamine: May enhance the CNS depressant effect of CNS depressants. Monitor therapy.
Dronabinol: CYP2C9 inhibitors (moderate) may increase the serum concentration of dronabinol. May enhance the CNS depressant effect of CNS depressants. Monitor therapy.
Droperidol: May enhance the CNS depressant effect of CNS depressants. Consider therapy modification.
Elvitegravir: Efavirenz may decrease the serum concentration of elvitegravir. Avoid combination.
Enzalutamide: CYP3A4 inducers (moderate) may decrease the serum concentration of enzalutamide. Avoid combination.
Etonogestrel: Efavirenz may diminish the therapeutic effect of etonogestrel. Consider therapy modification.
Etravirine: Reverse transcriptase inhibitors (non-nucleoside) may decrease the serum concentration of etravirine. This has been observed with NNRTIs efavirenz and nevirapine. Reverse transcriptase inhibitors (non-nucleoside) may increase the serum concentration of etravirine. This has been observed with delavirdine. Avoid combination.
Everolimus: Efavirenz may decrease the serum concentration of everolimus. Dose adjustment of everolimus may be required. Consider therapy modification.
Fentanyl: CYP3A4 inducers (moderate) may decrease the serum concentration of fentanyl. Monitor therapy.
Fosamprenavir: Efavirenz may decrease serum concentrations of the active metabolites of fosamprenavir. Consider therapy modification.
Fosphenytoin: May decrease the serum concentration of efavirenz. Efavirenz may increase the serum concentration of fosphenytoin. Consider therapy modification.
Ganciclovir, valganciclovir: May enhance the adverse/toxic effect of reverse transcriptase inhibitors (nucleoside). Ganciclovir-valganciclovir may increase the serum concentration of reverse transcriptase inhibitors (nucleoside). Consider therapy modification.
Ginkgo Biloba: May decrease the serum concentration of efavirenz. Monitor therapy.
Hydrocodone: CNS depressants may enhance the CNS depressant effect of hydrocodone. Consider therapy modification.
Hydroxyzine: May enhance the CNS depressant effect of CNS depressants. Monitor therapy.
Ibrutinib: CYP3A4 inducers (moderate) may decrease the serum concentration of ibrutinib. Consider therapy modification.
Ifosfamide: CYP3A4 inducers (moderate) may decrease serum concentrations of the active metabolites of ifosfamide. CYP3A4 inducers (moderate) may increase serum concentrations of the active metabolites of ifosfamide. Monitor therapy.
Indinavir: Efavirenz may decrease the serum concentration of indinavir. Consider therapy modification.
Itraconazole: Efavirenz may decrease the serum concentration of itraconazole. Avoid combination.
Kava Kava: May enhance the adverse/toxic effect of CNS depressants. Monitor therapy.
Ketoconazole (systemic): Efavirenz may decrease the serum concentration of ketoconazole (systemic). Avoid combination.
Lamivudine: May enhance the adverse/toxic effect of emtricitabine. Avoid combination.
Ledipasvir: May increase the serum concentration of tenofovir. Consider therapy modification.
Linagliptin: P-glycoprotein/ABCB1 inducers may decrease the serum concentration of linagliptin. Consider therapy modification.
Lopinavir: Efavirenz may decrease the serum concentration of lopinavir. Consider therapy modification.
Lovastatin: Efavirenz may decrease the serum concentration of lovastatin. Monitor therapy.
Magnesium sulfate: May enhance the CNS depressant effect of CNS depressants. Monitor therapy.
Maraviroc: Efavirenz may decrease the serum concentration of maraviroc. The combination of maraviroc and efavirenz is contraindicated in patients with CrCl less than 30 mL/min. Consider therapy modification.
Methadone: Reverse transcriptase inhibitors (non-nucleoside) may increase the metabolism of methadone. Consider therapy modification.
Methotrimeprazine: CNS depressants may enhance the CNS depressant effect of methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS depressants. Consider therapy modification.
Metyrosine: CNS depressants may enhance the sedative effect of metyrosine. Monitor therapy.
Mifepristone: May increase the serum concentration of efavirenz. Use efavirenz with caution, and monitor for increased adverse effects, during and 2 weeks following discontinuation of mifepristone. Monitor therapy.
Mirtazapine: CNS depressants may enhance the CNS depressant effect of mirtazapine. Monitor therapy.
Mitotane: May decrease the serum concentration of CYP3A4 substrates. Consider therapy modification.
Nabilone: May enhance the CNS depressant effect of CNS depressants. Monitor therapy.
Nevirapine: Efavirenz may enhance the adverse/toxic effect of nevirapine. Nevirapine may enhance the adverse/toxic effect of efavirenz. Nevirapine may decrease the serum concentration of efavirenz. Avoid combination.
Nisoldipine: CYP3A4 inducers (moderate) may decrease the serum concentration of nisoldipine. Avoid combination.
Nonsteroidal anti-inflammatory agents (NSAIDs): May enhance the adverse/toxic effect of tenofovir. Avoid use of tenofovir with high-dose or multiple NSAIDs when possible. Any use of NSAIDs in patients who are being treated with tenofovir should be undertaken with extra-caution and close monitoring for evidence of renal dysfunction. Consider therapy modification.
Norgestimate: Efavirenz may decrease serum concentrations of the active metabolites of norgestimate. Consider therapy modification.
Olaparib: CYP3A4 inducers (moderate) may decrease the serum concentration of olaparib. Avoid combination.
Ombitasvir: CYP3A4 inducers (moderate) may decrease the serum concentration of ombitasvir. Monitor therapy.
Orphenadrine: CNS depressants may enhance the CNS depressant effect of orphenadrine. Avoid combination.
Paraldehyde: CNS depressants may enhance the CNS depressant effect of paraldehyde. Avoid combination.
Paritaprevir: Efavirenz may enhance the adverse/toxic effect of paritaprevir. Efavirenz may decrease the serum concentration of paritaprevir. Avoid combination.
Perampanel: May enhance the CNS depressant effect of CNS depressants. Consider therapy modification.
P-glycoprotein/ABCB1 substrates: P-glycoprotein/ABCB1 inducers may decrease the serum concentration of P-glycoprotein/ABCB1 substrates. P-glycoprotein inducers may also further limit the distribution of P-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.) Monitor therapy.
Phenytoin: May decrease the serum concentration of efavirenz. Efavirenz may increase the serum concentration of phenytoin. Consider therapy modification.
Posaconazole: Efavirenz may decrease the serum concentration of posaconazole. Avoid combination.
Pramipexole: CNS depressants may enhance the sedative effect of pramipexole. Monitor therapy.
Pravastatin: Efavirenz may decrease the serum concentration of pravastatin. Monitor therapy.
Proguanil: Efavirenz may decrease the serum concentration of proguanil. Monitor therapy.
Quazepam: May increase the serum concentration of CYP2B6 substrates. Monitor therapy.
Raltegravir: Efavirenz may decrease the serum concentration of raltegravir. Monitor therapy.
Reverse transcriptase inhibitors (non-nucleoside): May increase the serum concentration of efavirenz. Reverse transcriptase inhibitors (non-nucleoside) may decrease the serum concentration of efavirenz. Avoid combination.
Ribavirin: May enhance the hepatotoxic effect of reverse transcriptase inhibitors (nucleoside). Lactic acidosis may occur. Consider therapy modification.
Rifabutin: May decrease the serum concentration of efavirenz. Efavirenz may decrease the serum concentration of rifabutin. Consider therapy modification.
Rifampin: May decrease the serum concentration of efavirenz. Consider therapy modification.
Rilpivirine: Reverse transcriptase inhibitor (non-nucleoside) may increase the serum concentration of rilpivirine. This mechanism applies to coadministration of delavirdine. Reverse transcriptase inhibitors (non-nucleoside) may decrease the serum concentration of rilpivirine. This mechanism applies to coadministration of efavirenz, etravirine, and nevirapine. Avoid combination.
Ritonavir: Efavirenz may enhance the adverse/toxic effect of ritonavir. Ritonavir may increase the serum concentration of efavirenz. Efavirenz may increase the serum concentration of ritonavir. Monitor therapy.
Ropinirole: CNS depressants may enhance the sedative effect of ropinirole. Monitor therapy.
Rotigotine: CNS depressants may enhance the sedative effect of rotigotine. Monitor therapy.
Rufinamide: May enhance the adverse/toxic effect of CNS depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy.
Saquinavir: May enhance the adverse/toxic effect of efavirenz. Efavirenz may decrease the serum concentration of saquinavir. Consider therapy modification.
Saxagliptin: CYP3A4 inducers may decrease the serum concentration of saxagliptin. Monitor therapy.
Selective serotonin reuptake inhibitors: CNS depressants may enhance the adverse/toxic effect of Selective serotonin reuptake inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy.
Sertraline: Efavirenz may decrease the serum concentration of sertraline. Monitor therapy.
Siltuximab: May decrease the serum concentration of CYP3A4 substrates. Monitor therapy.
Simeprevir: CYP3A4 inducers (moderate) may decrease the serum concentration of simeprevir. Avoid combination.
Simvastatin: Efavirenz may decrease the serum concentration of simvastatin. Monitor therapy.
Sirolimus: Efavirenz may decrease the serum concentration of sirolimus. Closely monitor sirolimus serum concentrations when starting, stopping, or changing doses of efavirenz, particularly during the first 2 weeks after any change. Dose adjustment of sirolimus may be required. Consider therapy modification.
Sodium oxybate: May enhance the CNS depressant effect of CNS depressants. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification.
St John's Wort: May decrease the serum concentration of efavirenz. Avoid combination.
Suvorexant: CNS depressants may enhance the CNS depressant effect of suvorexant. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification.
Tacrolimus (systemic): Efavirenz may decrease the serum concentration of tacrolimus (systemic). Dose adjustment of tacrolimus may be required. Consider therapy modification.
Tapentadol: May enhance the CNS depressant effect of CNS depressants. Monitor closely for evidence of excessive CNS depression. Consider therapy modification.
Telaprevir: May decrease the serum concentration of efavirenz. Efavirenz may decrease the serum concentration of telaprevir. Consider therapy modification.
Tetrahydrocannabinol: CYP2C9 inhibitors (moderate) may increase the serum concentration of tetrahydrocannabinol. Tetrahydrocannabinol may enhance the CNS depressant effect of CNS depressants. Monitor therapy.
Thalidomide: CNS depressants may enhance the CNS depressant effect of thalidomide. Avoid combination.
Tipranavir: May decrease the serum concentration of tenofovir. Tenofovir may decrease the serum concentration of tipranavir. Monitor therapy.
Tocilizumab: May decrease the serum concentration of CYP3A4 substrates. Monitor therapy.
Ulipristal: Efavirenz may decrease the serum concentration of ulipristal. Avoid combination.
Vincristine (liposomal): P-glycoprotein/ABCB1 inducers may decrease the serum concentration of vincristine (liposomal). Avoid combination.
Vitamin K antagonists (e.g., warfarin): Efavirenz may decrease the serum concentration of vitamin K antagonists. Efavirenz may increase the serum concentration of vitamin K antagonists. Monitor therapy.
Voriconazole: May increase the serum concentration of efavirenz. Efavirenz may decrease the serum concentration of voriconazole. Consider therapy modification.
Zolpidem: CNS depressants may enhance the CNS depressant effect of zolpidem. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification.
Drug-food interactions: Efavirenz: High-fat meals increase the absorption of efavirenz. CNS effects are possible. Management: Avoid high-fat meals.
Emtricitabine: Food decreases peak plasma concentrations, but does not alter the extent of absorption or overall systemic exposure. Management: administer without regard to meals.
Tenofovir: Fatty meals may increase the bioavailability of tenofovir. Management: may administer with or without food.
Storage
Do not store above 30°C. Store in the original container.
MIMS Class
ATC Classification
J05AR06 - emtricitabine, tenofovir disoproxil and efavirenz ; Belongs to the class of antivirals for treatment of HIV infections, combinations.
Presentation/Packing
FC tab (pink, biconvex, oblong, one side debossed with "TEE" and the other side plain) x 30's.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in