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Brand Name: Emtriva  |
Drug Class: Nucleoside Reverse Transcriptase Inhibitors
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Drug Description |
| Emtricitabine, also referred to as FTC, is a nucleoside reverse transcriptase inhibitor (NRTI). Emtricitabine is the (-) enantiomer of a thio analogue of cytidine; it differs from other cytidine analogues by a fluorine in the 5 position.[1] |
HIV/AIDS-Related Uses |
| Emtricitabine was approved by the FDA on July 2, 2003, for use in combination with other antiretroviral agents for the treatment of HIV-1 infection in adults. Emtricitabine oral solution was approved by the FDA on September 28, 2005, and is approved for use with other anti-HIV drugs for the treatment of HIV-1 infection in patients older than 3 months of age. Emtricitabine may be considered for treatment-experienced patients with HIV strains that are susceptible to emtricitabine as assessed by genotypic or phenotypic testing.[2] |
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Dosing Information |
Mode of Delivery |
| Oral (capsules, oral solution).[3] |
Dosage Form |
Capsules containing emtricitabine 200 mg.[4]
Oral solution containing emtricitabine 10 mg/ml.[5]
The recommended dose of emtricitabine for adults is 200 mg in capsule form or 240 mg (24 ml) oral solution once a day in combination with other antiretroviral agents. The recommended dose of emtricitabine for children is based on age and weight. Children who weigh more than 33 kg (72.8 lbs) and who can swallow an intact capsule should take 200 mg in capsule form once a day in combination with other antiretroviral agents.[6]
The dosing interval of emtricitabine in capsule form should be adjusted in patients with baseline creatinine clearance (CrCl) less than 50 ml/min as follows: 200 mg every 48 hours for CrCl 30 to 49 ml/min; 200 mg every 72 hours for CrCl 15 to 29 ml/min; and 200 mg every 96 hours for CrCl less than 15 ml/min. The dosing interval of emtricitabine oral solution should be adjusted with baseline CrCl less than 50 ml/min as follows: 120 mg (12 ml) every 24 hours for CrCl 30 to 49 ml/min; 80 mg (8 ml) every 24 hours for CrCl 15 to 29 ml/min; and 60 mg (6 ml) every 24 hours for CrCl less than 15 ml/min. There are insufficient data to recommend a specific dose adjustment of emtricitabine in pediatric patients with renal impairment, but a reduction in dose or an increase in the dosing interval similar to adjustments for adults should be considered for these patients. Patients taking emtricitabine concurrently with hemodialysis should receive emtricitabine 200 mg every 96 hours after the completion of dialysis.[7] |
Storage |
| Store capsules at 25 C (77 F); excursions permitted at 15 C to 30 C (59 F to 86 F). Store oral solution refrigerated between 2 C and 8 C (36 F to 46 F); oral solution should be used within 3 months if stored by the patient at 25 C (77 F), with excursions permitted at 15 C to 30 C (59 F to 86 F).[8] |
Pharmacology |
Emtricitabine, a synthetic nucleoside analogue of cytosine, undergoes phosphorylation by cellular enzymes to emtricitabine 5'-triphosphate. The active phosphate drug inhibits viral DNA synthesis by competing with the natural substrate deoxycytidine 5'-triphosphate for incorporation into viral DNA and by terminating the DNA chain at the point of incorporation.[9]
Emtricitabine is rapidly and extensively absorbed following oral administration, reaching peak plasma concentrations (Cmax) at 1 to 2 hours post dose. In one clinical trial, the mean absolute bioavailability of emtricitabine was 93% following multiple doses of the drug. The mean steady state Cmax was 1.8 mcg/ml, and the area under the plasma concentration-time curve (AUC) over a 24-hour dosing interval was 10 hr(mcg)/ml. The mean steady state plasma trough concentration 24 hours after an oral dose was 0.09 mcg/ml.[10]
Emtricitabine is in FDA Pregnancy Category B. Animal studies reveal no increased incidences of fetal variations or malformations in mice and rabbits at 60- and 120-fold higher drug exposures, respectively, than the human exposure at the recommended daily dose. However, there are no adequate and well-controlled studies in pregnant women. Results of animal studies are not always predictive of human response, and emtricitabine should be used during pregnancy only if clearly needed. An Antiretroviral Pregnancy Registry has been established to monitor fetal outcomes when the mother was exposed to antiretroviral drugs during pregnancy. Physicians can register patients online at http://www.APRegistry.com or by calling 1-800-258-4263. It is not known whether emtricitabine is distributed into human milk. Mothers should avoid nursing while taking emtricitabine.[11]
Emtricitabine is less than 4% bound to plasma proteins, and protein binding is independent of drug concentration over a range of 0.02 to 200 mcg/ml. In vitro studies indicate that emtricitabine does not inhibit CYP450 enzymes. Biotransformation occurs through glucuronidation and oxidation. Following administration of carbon-14-emtricitabine, 86% of the dose was recovered in urine and 14% in feces. Of the urine-recovered dose, 13% was recovered as metabolites, including 3'-sulfoxide diastereomers and 2'O-glucuronide. The plasma half-life of emtricitabine is approximately 10 hours. Renal clearance of the drug exceeds estimated creatinine clearance, indicating elimination by both glomerular filtration and active tubular secretion. In patients with renal impairment, both Cmax and AUC were increased.[12] Hemodialysis treatment removes about 30% of an emtricitabine dose over a 3-hour period, but it is unknown whether emtricitabine can be removed by peritoneal dialysis.[13]
HIV isolates with reduced susceptibility to emtricitabine have been recovered from some patients treated with emtricitabine alone or in combination with other antiretroviral agents. Viral isolates from 37.5% of patients with virologic failure had reduced susceptibility to emtricitabine, attributed to M184V/I mutations in the HIV reverse transcriptase gene. Cross resistance has been noted among some nucleoside analogues. Emtricitabine-resistant isolates were cross resistant to lamivudine and zalcitabine but retained susceptibility to abacavir, didanosine, stavudine, tenofovir, and zidovudine as well as to the non-nucleoside reverse transcriptase inhibitors delavirdine, efavirenz, and nevirapine. Viruses with mutations leading to decreased susceptibility to stavudine, zidovudine, or didanosine remained sensitive to emtricitabine. Isolates containing the K65R mutation demonstrated decreased susceptibility to emtricitabine.[14] |
Adverse Events/Toxicity |
The most frequently reported adverse effects of emtricitabine are mild to moderate headache, nausea, diarrhea, and skin rash. Skin discoloration on palms and soles was reported with higher frequency in emtricitabine-treated patients than in control groups, but the mechanism of skin discoloration is unknown.[15]
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including emtricitabine. In some patients coinfected with HIV and hepatitis B virus (HBV), exacerbation of hepatitis has been reported after discontinuing treatment with emtricitabine.[16]
Redistribution of body fat, peripheral wasting, facial wasting, breast enlargement, and cushingoid appearance have been observed in patients receiving antiretroviral therapy, including emtricitabine.[17]
Treatment-emergent Grade 3 or 4 laboratory abnormalities have been reported in at least 1% of patients receiving emtricitabine. These abnormalities include triglycerides greater than 750 mg/dl and creatine kinase more than four times the upper limit of normal.[18]
Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy, including emtricitabine. During the initial phase of combination antiretroviral treatment, a patient whose immune system improves may develop an inflammatory response to indolent or residual opportunistic infections, (e.g., Mycobacterium avium infection, cytomegalovirus infections, Pneumocystis jirovecii pneumonia, or tuberculosis), which may necessitate further evaluation and treatment.[19] |
Drug And Food Interactions |
Emtricitabine capsules and oral solution may be administered with or without food. AUC was unchanged and Cmax decreased by 29% when the capsule form of the drug was administered with a 1,000-calorie, high-fat meal. AUC and Cmax were unaffected when oral solution was administered with either a high- or low-fat meal.[20]
Emtricitabine has been evaluated in healthy volunteers in combination with tenofovir disoproxil fumarate (tenofovir DF), zidovudine, indinavir, famciclovir, and stavudine. A 20% increase in plasma trough concentrations of emtricitabine occurred when it was administered concurrently with tenofovir DF. When emtricitabine was given concurrently with zidovudine, zidovudine's AUC and Cmax increased by 13% and 17%, respectively.[21] Because renal elimination of emtricitabine is through glomerular filtration and active tubular secretion, there may be competition for elimination with other compounds that are also renally eliminated.[22] |
Contraindications |
| Emtricitabine is contraindicated in patients with previously demonstrated hypersensitivity to any of the components of the drug product. Emtricitabine should be discontinued in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or severe hepatotoxicity. There have been reports of severe acute exacerbations of hepatitis B after discontinuation of emtricitabine treatment in patients coinfected with HIV and HBV; hepatic function should be monitored closely for at least several months after discontinuing emtricitabine in such patients.[23] |
Clinical Trials |
| Click here to search ClinicalTrials.gov for trials that use Emtricitabine. |
Chemistry |
CAS Name |
| (2R-cis)-4-Amino-5-fluoro- 1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl] -2(1H)-pyrimidinone[24] |
CAS Number |
| 143491-57-0[25] |
Molecular Formula |
| C8-H10-F-N3-O3-S[26] |
Elemental Composition |
| C38.86%, H4.08%, F7.68%, N17.00%, O19.41%, S12.97%[27] |
Molecular Weight |
| 247.25[28] |
Melting Point |
| 136 C to 140 C as solid white from ether and methanol[29] |
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Physical Description |
| White to off-white powder.[30] |
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Solubility |
| Approximately 112 mg/ml in water at 25 C (77 F).[31] |
Other Names |
FTC[32]
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Further Reading |
Emtriva Prescribing Information from the FDA Web site [PDF]. A more current version may be available on the manufacturer's Web site.
PMID/17725415 Borroto-Esoda K, Waters JM, Bae AS, Harris JL, Hinkle JE, Quinn JB, Rousseau FS. Baseline genotype as a predictor of virological failure to emtricitabine or stavudine in combination with didanosine and efavirenz. AIDS Res Hum Retroviruses. 2007 Aug;23(8):988-95
PMID/16764056 Jenny-Avital ER. Tenofovir DF and emtricitabine vs. zidovudine and lamivudine. N Engl J Med. 2006 Jun 8;354(23):2506-8; author reply 2506-8. No abstract available.
PMID/17058783 Marconi P, Lorenzini P, Borrelli I, Liuzzi G, Sette P, Zaccarelli M, Antinori A. Safety and efficacy of regimens containing emtricitabine in HIV-infected patients taking highly active antiretroviral therapy.New Microbiol. 2006 Jul;29(3):169-75.
PMID/17646352 McKinney RE Jr, Rodman J, Hu C, Britto P, Hughes M, Smith ME, Serchuck LK, Kraimer J, Ortiz AA, Flynn P, Yogev R, Spector S, Draper L, Tran P, Scites M, Dickover R, Weinberg A, Cunningham C, Abrams E, Blum MR, Chittick GE, Reynolds L, Rathore M; Pediatric AIDS Clinical Trials Group Protocol P1021 Study Team. Long-term safety and efficacy of a once-daily regimen of emtricitabine, didanosine, and efavirenz in HIV-infected, therapy-naive children and adolescents: Pediatric AIDS Clinical Trials Group Protocol P1021. Pediatrics. 2007 Aug;120(2):e416-23. Epub 2007 Jul 23.
PMID/17591032 Molina JM, Journot V, Furco A, Palmer P, De Castro N, Raffi F, Morlat P, May T, Rancinan C, Chene G; Montana (ANRS 091) Study Group. Five-year follow up of once-daily therapy with emtricitabine, didanosine and efavirenz (Montana ANRS 091 trial). Antivir Ther. 2007;12(3):417-22.
PMID/16323102 Saag MS. Emtricitabine, a new antiretroviral agent with activity against HIV and hepatitis B virus. Clin Infect Dis. 2006 Jan 1;42(1):126-31. Epub 2005 Nov 23. Review.
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Manufacturer Information |
Emtricitabine
Gilead Sciences Inc
333 Lakeside Dr
Foster City, CA 94404
(800) 445-3235
Emtriva
Gilead Sciences Inc
333 Lakeside Dr
Foster City, CA 94404
(800) 445-3235
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References |
[1] FDA - Emtriva Prescribing Information, December 2006, p. 3. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[2] FDA - Emtriva Prescribing Information, December 2006, pp. 3-4. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[3] FDA - Emtriva Prescribing Information, December 2006, p. 3. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[4] FDA - Emtriva Prescribing Information, December 2006, p. 23. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[5] FDA - Emtriva Prescribing Information, December 2006, p. 23. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[6] FDA - Emtriva Prescribing Information, December 2006, p. 22. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[7] FDA - Emtriva Prescribing Information, December 2006, pp. 22-3. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[8] FDA - Emtriva Prescribing Information, December 2006, p. 23. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[9] FDA - Emtriva Prescribing Information, December 2006, p. 4. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[10] FDA - Emtriva Prescribing Information, December 2006, pp. 5-6. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[11] FDA - Emtriva Prescribing Information, December 2006, pp. 15-6. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[12] FDA - Emtriva Prescribing Information, December 2006, pp. 6-7. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[13] FDA - Emtriva Prescribing Information, December 2006, p. 8. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[14] FDA - Emtriva Prescribing Information, December 2006, pp. 4-5. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[15] FDA - Emtriva Prescribing Information, December 2006, p. 27. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[16] FDA - Emtriva Prescribing Information, December 2006, p. 13. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[17] FDA - Emtriva Prescribing Information, December 2006, p. 14. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[18] FDA - Emtriva Prescribing Information, December 2006, p. 19. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[19] FDA - Emtriva Prescribing Information, December 2006, p. 14. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[20] FDA - Emtriva Prescribing Information, December 2006, p. 6. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[21] FDA - Emtriva Prescribing Information, December 2006, pp. 8-9. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[22] FDA - Emtriva Prescribing Information, December 2006, p. 6. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[23] FDA - Emtriva Prescribing Information, December 2006, p. 13. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[24] ChemIDplus - Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 12/20/07.
[25] ChemIDplus - Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 12/20/07.
[26] ChemIDplus - Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 12/20/07.
[27] Merck Index - 2006; p. 607
[28] Merck Index - 2006; p. 607
[29] Merck Index - 2006; p. 607
[30] FDA - Emtriva Prescribing Information, December 2006, p. 3. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[31] FDA - Emtriva Prescribing Information, December 2006, p. 3. Available at: http://www.fda.gov/cder/foi/label/2006/021896s001,021500s007lbl.pdf. Accessed 12/20/07.
[32] ChemIDplus - Available at: http://chem.sis.nlm.nih.gov/chemidplus/chemidlite.jsp. Accessed 12/20/07.
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Updated December 20, 2007
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