Emtricitabine

Pronunciation

(em trye SYE ta been)

U.S. Brand Names

Emtriva™

Synonyms

BW524W91; Coviracil; FTC

Generic Available

No

Use

Treatment of HIV infection in combination with at least two other antiretroviral agents

Use - Unlabeled/Investigational

Investigational: Hepatitis B

Pregnancy Risk Factor

B

Pregnancy Implications

Cases of fatal and nonfatal lactic acidosis, with or without pancreatitis, have been reported in pregnant women receiving reverse transcriptase inhibitors. It is not known if pregnancy itself potentiates this known side effect; however, pregnant women may be at increased risk of lactic acidosis and liver damage. Hepatic enzymes and electrolytes should be monitored frequently during the 3rd trimester of pregnancy. There are no studies of emtricitabine during pregnancy. The Perinatal HIV Guidelines Working Group considers emtricitabine to be an alternative NRTI in dual nucleoside combination regimens. Health professionals are encouraged to contact the antiretroviral pregnancy registry to monitor outcomes of pregnant women exposed to antiretroviral medications (1-800-258-4263 or www.APRegistry.com).

Lactation

Excretion in breast milk unknown/not recommended

Contraindications

Hypersensitivity to emtricitabine or any component of the formulation

Warnings/Precautions

Lactic acidosis, severe hepatomegaly, and hepatic failure have occurred rarely with emtricitabine (similar to other nucleoside analogues). Some cases have been fatal; stop treatment if lactic acidosis or hepatotoxicity occur. Prior liver disease, obesity, extended duration of therapy, and female gender may represent risk factors for severe hepatic reactions. Testing for hepatitis B is recommended prior to the initiation of therapy; hepatitis B may be exacerbated following discontinuation of emtricitabine. Use caution in patients with renal impairment (dosage adjustment required).

Adverse Reactions

Clinical trials were conducted in patients receiving other antiretroviral agents, and it is not possible to correlate frequency of adverse events with emtricitabine alone. The range of frequencies of adverse events is generally comparable to comparator groups, with the exception of hyperpigmentation, which occurred more frequently in patients receiving emtricitabine.

>10%:

Central nervous system: Headache (13% to 22%), dizziness (4% to 25%), insomnia (7% to 16%)

Dermatologic: Rash (17% to 30%; includes rash, pruritus, maculopapular rash, vesiculobullous rash, pustular rash, and allergic reaction)

Gastrointestinal: Diarrhea (23%), nausea (13% to 18%), abdominal pain (8% to 14%)

Neuromuscular & skeletal: Weakness (12% to 16%), CPK increased (11% to 12%)

Respiratory: Cough (14%), rhinitis (12% to 18%)

1% to 10%:

Central nervous system: Abnormal dreams (2% to 11%), depression (6% to 9%), neuropathy/neuritis (4%)

Dermatologic: Hyperpigmentation (2% to 6%; primarily of palms and/or soles but may include tongue, arms, lip and nails; generally mild and nonprogressive without associated local reactions such as pruritus or rash)

Endocrine & metabolic: Serum triglycerides increased (9% to 10%), disordered glucose homeostasis (2% to 3%), serum amylase increased (2% to 5%)

Gastrointestinal: Dyspepsia (4% to 8%), vomiting (9%)

Hepatic: Transaminases increased (2% to 6%), bilirubin increased (1%)

Neuromuscular & skeletal: Myalgia (4% to 6%), arthralgia (3% to 5%), paresthesia (5% to 6%)

Overdosage/Toxicology

Treatment is supportive and symptom-directed. Approximately 30% of a dose is removed by hemodialysis.

Drug Interactions

Note: Limited drug interaction data available. No evidence of a clinically-significant interaction when administered with tenofovir, indinavir, famciclovir, or stavudine.

Ribavirin: Concomitant use of ribavirin and nucleoside analogues may increase the risk of developing lactic acidosis.

Ethanol/Nutrition/Herb Interactions

Food: Food decreases peak plasma concentrations, but does not alter the extent of absorption or overall systemic exposure.

Stability

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

Mechanism of Action

Nucleoside reverse transcriptase inhibitor; emtricitabine is a cytosine analogue which is phosphorylated intracellularly to emtricitabine 5'-triphosphate which interferes with HIV viral RNA dependent DNA polymerase resulting in inhibition of viral replication.

Pharmacodynamics/Kinetics

Absorption: Rapid, extensive

Protein binding: <4%

Metabolism: Limited, via oxidation and conjugation (not via CYP isoenzymes)

Bioavailability: 93%

Half-life elimination: Normal renal function: 10 hours

Time to peak, plasma: 1-2 hours

Excretion: Urine (86% primarily as unchanged drug, 13% as metabolites); feces (14%)

Dosage

Oral: Adults: 200 mg once daily

Dosage adjustment in renal impairment:

Clcr 30-49 mL/minute: 200 mg every 48 hours

Clcr 15-29 mL/minute: 200 mg every 72 hours

Clcr<15 mL/minute (including hemodialysis patients): 200 mg every 96 hours

Dosage adjustment in hepatic impairment: No adjustment required.

Administration

May be administered with or without food.

Monitoring Parameters

Viral load, CD4, liver function tests; hepatitis B testing is recommended prior to initiation of therapy

Dietary Considerations

May be taken with or without food.

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy without consulting prescriber (you will be provided with a list of specific medications that should not be used). This is not a cure for HIV, nor has it been found to reduce transmission of HIV. Take as directed. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. Emtricitabine is prescribed with a combination of other medications; time these medications as directed by prescriber. May cause headache, dizziness, or insomnia (use caution when driving or engaging in hazardous tasks until response to drug is known); nausea, vomiting, or abdominal discomfort (small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); diarrhea (consult prescriber if persistent); muscle or skeletal pain (consult prescriber for approved analgesic). Report respiratory difficulty, rash, or any persistent adverse effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Breast-feeding is not recommended.

Dental Health: Effects on Dental Treatment

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

Insomnia and dizziness are common; may cause depression and abnormal dreams

Mental Health: Effects on Psychiatric Treatment

GI side effects are common. Combined use with SSRIs may produce additive effects. May cause increases in serum triglycerides. Monitor in patients receiving concurrent psychotropic medication especially, clozapine, olanzapine, quetiapine, or mirtazapine. May cause glucose abnormalities; use caution with clozapine, olanzapine, and quetiapine, and risperidone.

Dosage Forms

Capsule: 200 mg

References

Cahn P, Raffi F, Saag M, et al, "Virologic Efficacy and Patterns of Resistance Mutations in ART-Naive Patients Receiving Combination Therapy with Once-Daily (QD) Emtricitabine Compared to Twice-Daily (BID) Stavudine in a Randomized, Double-blind, Multi-center Clinical Trial (Poster 606)," Presented at the 10th Conference on Retroviruses and Opportunistic Infections, Boston, MA, February 10-14, 2003. Available at: http://www.retroconference.org/Archive/Posters/Retro10/606.pdf. Accessed July 9, 2003.

Gish RG, Leung NW, Wright TL, et al, "Dose Range Study of Pharmacokinetics, Safety, and Preliminary Antiviral Activity of Emtricitabine in Adults With Hepatitis B Virus Infection,"Antimicrob Agents Chemother, 2002, 46(6):1734-40.

"Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV-1 Transmission in the United States," June 23, 2004. Available at: http://www.aidsinfo.nih.gov. Accessed July 1, 2004.

Saag M, Cahn P, Raffi F, et al, "A Randomized, Double-Blind, Multicenter Comparison of Emtricitabine QD to Stavudine BID (Oral Presentation LB-1)," Presented at the 42nd International Conference on Antimicrobial Agents and Chemotherapy, San Diego, CA, September 27-20, 2002.

Sanne I, van der Horst C, Shaw A, et al, "Two Randomized, Controlled, Equivalence Trials of Emtricitabine (FTC) to Lamivudine (3TC)," Presented at the 14th International AIDS Conference, Barcelona, Spain, July 7-12, 2002. Available at: http://www.aids2002.com/Program/ViewAbstract.asp?id=/T-CMS_Content/Abstract/200 Accessed July 9, 2003.

International Brand Names

Emtriva® (AT, AU, BE, CY, DE, DK, ES, FI, FR, GB, GR, HU, IE, IS, IT, JP, LT, LU, LV, MT, NL, NO, PL, PT, SE, SI, SK)