Trivenz

Each tablet contains 600 mg of Efavirenz (Trivenz), 200 mg of Emtricitabine (Trivenz), and 300 mg of Tenofovir (Trivenz) disoproxil fumarate (Tenofovir (Trivenz) DF, which is equivalent to 245 mg of Tenofovir (Trivenz) disoproxil).

Trivenz is a fixed-dose combination tablet containing Trivenz disoproxil fumarate (Tenofovir (Trivenz) DF). Efavirenz (Trivenz) is a non-nucleoside reverse transcriptase inhibitor. Emtricitabine (Trivenz) is a synthetic nucleoside analog of cytidine. VIREAD is the brand name for Tenofovir (Trivenz) DF, which is converted in vivo to Tenofovir (Trivenz), an acyclic nucleoside phosphonate (nucleotide) analog of adenosine 5′-monophosphate. VIREAD and Emtricitabine (Trivenz) are the components of TRUVADA.

Efavirenz (Trivenz): Efavirenz (Trivenz) is chemically described as (S)-6-chloro-4-(cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one. Its molecular formula is C₁₄H₉ClF₃NO₂.

Efavirenz (Trivenz) is a white to slightly pink crystalline powder with a molecular mass of 315.68. It is practically insoluble in water (less than 10 μg/mL).

Emtricitabine (Trivenz): The chemical name of Emtricitabine (Trivenz) is 5-fluoro-1-(2R,5S)-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine. Emtricitabine (Trivenz) is the (-) enantiomer of a thio analog of cytidine, which differs from other cytidine analogs in that it has a fluorine in the 5-position.

It has a molecular formula of C₈H₁₀FN₃O₃S and a molecular weight of 247.24.

Emtricitabine (Trivenz) is a white to off-white crystalline powder with a solubility of approximately 112 mg/mL in water at 25°C.

Tenofovir (Trivenz) Disoproxil Fumarate: Tenofovir (Trivenz) DF is a fumaric acid salt of the bis-isopropoxycarbonyloxymethyl ester derivative of Tenofovir (Trivenz). The chemical name of Tenofovir (Trivenz) disoproxil fumarate is 9-[(R)-2[[bis[[(isopropoxycarbonyl)oxy]-methoxy]phosphinyl]methoxy]propyl]adenine fumarate (1:1). It has a molecular formula of C₁₉H₃₀N₅O₁₀P·C₄H₄O₄ and a molecular weight of 635.52.

Tenofovir (Trivenz) DF is a white to off-white crystalline powder with a solubility of 13.4 mg/mL in water at 25°C.

Excipients/Inactive Ingredients: Croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose and sodium lauryl sulfate. The tablets are film-coated with a coating material containing black iron oxide, polyethylene glycol, polyvinyl alcohol, red iron oxide, talc, and titanium dioxide.

Trivenz® 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.

Trivenz combination is used alone or with other anti-HIV medicines to treat human immunodeficiency virus (HIV) infection. HIV is the virus that causes acquired immune deficiency syndrome (AIDS).

Trivenz does not cure or prevent HIV or AIDS. It helps keep HIV from reproducing and appears to slow down the destruction of the immune system. This may help delay the development of problems that usually result from AIDS or HIV disease. It will not keep you from spreading HIV to other people. People who receive Trivenz may continue to have some of the problems usually related to AIDS or HIV disease.

Trivenz is available only with your doctor's prescription.

Adults and pediatric patients 12 years of age and older with body weight at least 40 kg (at least 88 lbs)

The dose of Trivenz is one tablet once daily taken orally on an empty stomach. Dosing at bedtime may improve the tolerability of nervous system symptoms.

Renal Impairment

Because Trivenz is a fixed-dose combination, it should not be prescribed for patients requiring dosage adjustment such as those with moderate or severe renal impairment (estimated creatinine clearance below 50 mL/min).

Rifampin Coadministration

When Trivenz is administered with rifampin to patients weighing 50 kg or more, an additional 200 mg/day of Efavirenz (Trivenz) is recommended.

How supplied

Dosage Forms And Strengths

Trivenz is available as tablets. Each tablet contains 600 mg of Efavirenz (Trivenz), 200 mg of Emtricitabine (Trivenz) and 300 mg of Tenofovir (Trivenz) disoproxil fumarate (Tenofovir (Trivenz) DF, which is equivalent to 245 mg of Tenofovir (Trivenz) disoproxil). The tablets are pink, capsule-shaped, film-coated, debossed with “123” on one side and plain-faced on the other side.

Storage And Handling

Trivenz tablets are pink, capsule-shaped, film-coated, debossed with “123” on one side and plain-faced on the other side. Each bottle contains 30 tablets (NDC 15584-0101-1) and silica gel desiccant, and is closed with a child-resistant closure.

Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F).

• Keep container tightly closed.
• Dispense only in original container.
• Do not use if seal over bottle opening is broken or missing.

Bristol-Myers Squibb & Gilead Sciences, LLC. Revised: November 2015

See also:
What is the most important information I should know about Trivenz?

Hypersensitivity: Trivenz is contraindicated in patients with previously demonstrated clinically significant hypersensitivity (e.g., Stevens-Johnson syndrome, erythema multiforme, or toxic skin eruptions) to Efavirenz (Trivenz), a component of Trivenz.

Contraindicated Drugs: Coadministration of Trivenz with voriconazole is contraindicated. Efavirenz (Trivenz), a component of Trivenz, significantly decreases voriconazole plasma concentrations, and coadministration may decrease the therapeutic effectiveness of voriconazole. Also, voriconazole significantly increases Efavirenz (Trivenz) plasma concentrations, which may increase the risk of Efavirenz (Trivenz)-associated side effects. Because Trivenz is a fixed-dose combination product, the dose of Efavirenz (Trivenz) cannot be altered.

Use Trivenz as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Trivenz. Talk to your pharmacist if you have questions about this information.
• Take Trivenz by mouth on an empty stomach at least 1 hour before or 2 hours after eating.
• Take Trivenz with a full glass of water (8 oz [240 mL]).
• Do not take Trivenz if the seal over the bottle opening is broken or missing.
• Continue to take Trivenz even if you feel well. Do not miss any doses.
• Take Trivenz at the same time each day, preferably at bedtime, unless otherwise directed by your doctor.
• If you miss a dose of Trivenz, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Trivenz.

Use: Labeled Indications

HIV-1 infection, treatment: Treatment of HIV-1 infection in adult and pediatric patients weighing ≥40 kg (may be used alone or in combination with other antiretroviral agents).

See also:
What other drugs will affect Trivenz?

This section describes clinically relevant drug interactions with Trivenz. Drug interaction trials are described elsewhere in the monograph.

Efavirenz (Trivenz): Efavirenz (Trivenz) has been shown in vivo to induce CYP3A and CYP2B6. Other compounds that are substrates of CYP3A or CYP2B6 may have decreased plasma concentrations when coadministered with Efavirenz (Trivenz).

Drugs that induce CYP3A activity (e.g., phenobarbital, rifampin, rifabutin) would be expected to increase the clearance of Efavirenz (Trivenz), resulting in lowered plasma concentrations.

Emtricitabine (Trivenz) and Tenofovir (Trivenz) Disoproxil Fumarate: Since Emtricitabine (Trivenz) and Tenofovir (Trivenz) are primarily eliminated by the kidneys, coadministration of Trivenz with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of Emtricitabine (Trivenz), Tenofovir (Trivenz), and/or other renally eliminated drugs. Some examples include, but are not limited to, acyclovir, adefovir dipivoxil, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs.

Coadministration of Tenofovir (Trivenz) DF and didanosine should be undertaken with caution and patients receiving this combination should be monitored closely for didanosine-associated adverse reactions. Didanosine should be discontinued in patients who develop didanosine-associated adverse reactions. Suppression of CD4⁺ cell counts has been observed in patients receiving Tenofovir (Trivenz) DF with didanosine 400 mg daily.

Darunavir with ritonavir and lopinavir/ritonavir have been shown to increase Tenofovir (Trivenz) concentrations. Tenofovir (Trivenz) DF is a substrate of P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) transporters. When Tenofovir (Trivenz) DF is coadministered with an inhibitor of these transporters, an increase in absorption may be observed. Patients receiving darunavir with ritonavir and Trivenz, or lopinavir/ritonavir with Trivenz, should be monitored for Tenofovir (Trivenz)-associated adverse reactions. Trivenz should be discontinued in patients who develop Tenofovir (Trivenz)-associated adverse reactions.

Coadministration of atazanavir with Trivenz is not recommended since coadministration of atazanavir with either Efavirenz (Trivenz) or Tenofovir (Trivenz) DF has been shown to decrease plasma concentrations of atazanavir. Also, atazanavir has been shown to increase Tenofovir (Trivenz) concentrations. There are insufficient data to support dosing recommendations for atazanavir or atazanavir/ritonavir in combination with Trivenz.

Efavirenz (Trivenz), Emtricitabine (Trivenz) and Tenofovir (Trivenz) Disoproxil Fumarate: Other important drug interaction information for Trivenz is summarized in Table 8. The drug interactions described are based on trials conducted with Efavirenz (Trivenz), Emtricitabine (Trivenz) or Tenofovir (Trivenz) DF as individual agents or are potential drug interactions; no drug interaction trials have been conducted using Trivenz. The tables include potentially significant interactions, but are not all inclusive.

Efavirenz (Trivenz) Assay Interference: Cannabinoid Test Interaction: Efavirenz (Trivenz) does not bind to cannabinoid receptors. False-positive urine cannabinoid test results have been reported with some screening assays in uninfected and HIV-infected subjects receiving Efavirenz (Trivenz). Confirmation of positive screening tests for cannabinoids by a more specific method is recommended.

See also:
What are the possible side effects of Trivenz?

Efavirenz (Trivenz), Emtricitabine (Trivenz) and Tenofovir (Trivenz) Disoproxil Fumarate: The following adverse reactions are discussed in other sections: Lactic Acidosis/Severe Hepatomegaly with Steatosis, severe acute exacerbations of hepatitis B; Psychiatric Symptoms, Nervous System Symptoms, New-Onset or Worsening Renal Impairment, Rash, Decreases in Bone Mineral Density, Immune Reconstitution Syndrome; Drug Interactions.

For additional safety information about Sustiva or Stocrin (Efavirenz (Trivenz)), Emtriva (Emtricitabine (Trivenz)) or Viread (Tenofovir (Trivenz) DF) in combination with other antiretroviral agents, refer to the prescribing information for these products.

Adverse Reactions from Clinical Trials Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Study 934: Study 934 was an open-label active-controlled study in which 511 antiretroviral-naive subjects received either Emtricitabine (Trivenz) + Tenofovir (Trivenz) DF administered in combination with Efavirenz (Trivenz) (N=257) or zidovudine/lamivudine administered in combination with Efavirenz (Trivenz) (N=254).

The most common adverse reactions (incidence ≥10%, any severity) occurring in Study 934 include diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams and rash. Adverse reactions observed in Study 934 were generally consistent with those seen in previous studies of the individual components.

Study 073: In Study 073, subjects with stable, virologic suppression on antiretroviral therapy and no history of virologic failure were randomized to receive Trivenz or to stay on their baseline regimen. The adverse reactions observed in Study 073 were generally consistent with those seen in Study 934 and those seen with the individual components of Trivenz when each was administered in combination with other antiretroviral agents.

Efavirenz (Trivenz), Emtricitabine (Trivenz) or Tenofovir (Trivenz) Disoproxil Fumarate: In addition to the adverse reactions in Study 934 and Study 073 the following adverse reactions were observed in clinical trials of Efavirenz (Trivenz), Emtricitabine (Trivenz) or Tenofovir (Trivenz) DF in combination with other antiretroviral agents.

Efavirenz (Trivenz): The most significant adverse reactions observed in subjects treated with Efavirenz (Trivenz) are nervous system symptoms, psychiatric symptoms and rash.

Selected adverse reactions of moderate to severe intensity observed in ≥2% of Efavirenz (Trivenz)-treated subjects in 2 controlled clinical trials included pain, impaired concentration, abnormal dreams, somnolence, anorexia, dyspepsia, abdominal pain, nervousness and pruritus.

Pancreatitis has also been reported, although a causal relationship with Efavirenz (Trivenz) has not been established. Asymptomatic increases in serum amylase levels were observed in a significantly higher number of subjects treated with Efavirenz (Trivenz) 600 mg than in control subjects.

Emtricitabine (Trivenz) and Tenofovir (Trivenz) Disoproxil Fumarate: Adverse reactions that occurred in at least 5% of treatment-experienced or treatment-naive patients receiving Emtricitabine (Trivenz) or Tenofovir (Trivenz) DF with other antiretroviral agents in clinical trials include arthralgia, increased cough, dyspepsia, fever, myalgia, pain, abdominal pain, back pain, paresthesia, peripheral neuropathy (including peripheral neuritis and neuropathy), pneumonia, rhinitis and rash event (including rash, pruritus, maculopapular rash, urticaria, vesiculobullous rash, pustular rash and allergic reaction).

Skin discoloration has been reported with higher frequency among Emtricitabine (Trivenz)-treated subjects; it was manifested by hyperpigmentation on the palms and/or soles and was generally mild and asymptomatic. The mechanism and clinical significance are unknown.

Laboratory Abnormalities: Efavirenz (Trivenz), Emtricitabine (Trivenz) and Tenofovir (Trivenz) Disoproxil Fumarate: Laboratory abnormalities observed in Study 934 were generally consistent with those seen in previous studies.

Laboratory abnormalities observed in Study 073 were generally consistent with those in Study 934.

In addition to the laboratory abnormalities described for Study 934, grade 3/4 elevations of bilirubin (>2.5 x ULN), pancreatic amylase (>2 x ULN), serum glucose (<40 or >250 mg/dL) and serum lipase (>2 x ULN) occurred in up to 3% of subjects treated with Emtricitabine (Trivenz) or Tenofovir (Trivenz) DF with other antiretroviral agents in clinical trials.

Hepatic Events: In Study 934, 19 subjects treated with Efavirenz (Trivenz), Emtricitabine (Trivenz) and Tenofovir (Trivenz) DF and 20 subjects treated with Efavirenz (Trivenz) and fixed-dose zidovudine/lamivudine were hepatitis B surface antigen or hepatitis C antibody positive. Among these co-infected subjects, 1 subject (1/19) in the Efavirenz (Trivenz), Emtricitabine (Trivenz) and Tenofovir (Trivenz) DF arm had elevations in transaminases to >5 x ULN through 144 weeks. In the fixed-dose zidovudine/lamivudine arm, 2 subjects (2/20) had elevations in transaminases to >5 x ULN through 144 weeks. No HBV and/or HCV co-infected subject discontinued from the study due to hepatobiliary disorders.

Post-Marketing Experience: The following adverse reactions have been identified during post-approval use of Efavirenz (Trivenz), Emtricitabine (Trivenz) or Tenofovir (Trivenz) DF. Because post-marketing reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Efavirenz (Trivenz): Cardiac Disorders: Palpitations.

Ear and Labyrinth Disorders: Tinnitus.

Endocrine Disorders: Gynecomastia.

Eye Disorders: Abnormal vision.

Gastrointestinal Disorders: Constipation, malabsorption.

General Disorders and Administration Site Conditions: Asthenia.

Hepatobiliary Disorders: Increased hepatic enzyme, hepatic failure, hepatitis.

Immune System Disorders: Allergic reactions.

Metabolism and Nutrition Disorders: Re-distribution/accumulation of body fat, hypercholesterolemia, hypertriglyceridemia.

Musculoskeletal and Connective Tissue Disorders: Arthralgia, myalgia, myopathy.

Nervous System Disorders: Abnormal coordination, ataxia, cerebellar coordination and balance disturbances, convulsions, hypoesthesia, paresthesia, neuropathy, tremor.

Psychiatric Disorders: Aggressive reactions, agitation, delusions, emotional lability, mania, neurosis, paranoia, psychosis, suicide.

Respiratory, Thoracic and Mediastinal Disorders: Dyspnea.

Skin and Subcutaneous Tissue Disorders: Flushing, erythema multiforme, photoallergic dermatitis, Stevens-Johnson syndrome.

Emtricitabine (Trivenz): No post-marketing adverse reactions have been identified for inclusion in this section.

Tenofovir (Trivenz) Disoproxil Fumarate: 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, γ-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.

General Disorders and Administration Site Conditions: Asthenia.

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