Emtricitabine (Emtriva), short name FTC, is a nucleoside reverse transcriptase inhibitor used for the prophylaxis and treatment of HIV-1 infection in children and adults.

Indications of Emtricitabine:

• HIV-1 infection, treatment:

  • It is indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents.

• Off-Label Use of Emtricitabine in Adults:

  • HIV-1 nonoccupational postexposure prophylaxis.
  • HIV-1 occupational post-exposure prophylaxis.

Emtricitabine dose in adults:

Emtricitabine Dosage in the treatement of HIV-1 infection:

• Capsule: 200 mg per oral once daily.
• Solution: 240 mg per oral once daily.

Emtricitabine Dose in the postexposure prophylaxis of nonoccupational HIV-1 (nPEP) (off-label):

• Capsule: 200 mg per oral once daily.
• Therapy should be started in combination with other antiretroviral drugs within 72 hours of exposure and continued for 28 days (3-drug regimen).
• Note: The fixed-dose emtricitabine and tenofovir disoproxil fumarate combination product is recommended for these components of the 3-drug regimen.

Emtricitabine Dose in the postexposure prophylaxis of occupational HIV-1 (oPEP):

• Capsule: 200 mg per oral once daily in combination with tenofovir disoproxil fumarate and raltegravir.
• Therapy should be started as soon as possible after occupational exposure (and within 72 hours) and continued for 4 weeks.
• Note: The fixed-dose emtricitabine and tenofovir disoproxil fumarate combination product is recommended for these components of the regimen.

Dose in children:

Note: Due to bioavailability differences dosage forms are not bioequivalent; oral solution and capsules should not be interchanged on mg: mg basis.

Emtricitabine dose in children:

Emtricitabine Dose in the treatment of HIV-1 infection:

Note: Use in combination with other antiretroviral agents.

• Infants 1 to <3 months:

  • Oral solution: 3 mg/kg/dose once daily

• Infants ≥3 months, Children, and Adolescents ≤17 years:

  • Oral solution: 6 mg/kg/dose once daily.
  • maximum daily dose: 240 mg/day.
  • Capsules: Patient weight >33 kg and able to swallow capsule whole: 200 mg once daily

• Adolescents ≥18 years:

  • Capsules: 200 mg once daily.
  • Oral solution: 240 mg once daily.

Emtricitabine Dose in the treatment of HIV-1 nonoccupational postexposure prophylaxis (nPEP):

Note: Combination therapy should be started orally within 72 hours of exposure and continue for 28 days.

• Infants 1 to <3 months:

  • Oral solution: 3 mg/kg/dose once daily.

• Infants ≥3 months and Children:

  • Oral solution: 6 mg/kg/dose once daily.
  • maximum daily dose: 240 mg/day.
  • Capsules: Patient weight >33 kg and able to swallow capsule whole: 200 mg once daily.

• Adolescents:

  • The combination product is recommended [see emtricitabine and tenofovir disoproxil fumarate monograph].

Pregnancy Risk Category: B

• Emtricitabine can cross the human placenta.
• Antiviral therapy during pregnancy was not associated with an increased risk of birth defects.
• Preterm births can be more likely depending on several factors, including maternal health and gestational age at therapy initiation. However, data are limited.
• Some studies showed an increase in stillbirths, low birth weight and infants of gestational age who were smaller than expected.
• It is important to continue maternal therapy during pregnancy, as it has more advantages than negative neonatal outcomes.
• Maternal antiviral therapy should be administered to infants. Infants with severe organ system abnormalities (especially the heart or CNS) should be monitored for the long-term.
• NRTIs have been shown to cause lactic acidosis, hepatic inflammation and mitochondrial toxicity.
• Although fatal conditions like HELLP syndrome are possible, NRTIs can be tolerated well and the benefits generally outweigh any potential risks.
• During pregnancy, patients who are antiretroviral-naive, who have had ART therapy in the past but are restarting, who require a new ART regimen (due to poor tolerance or poor virologic response of current regimen), and who are planning for conception, emtricitabine is the preferred antiviral agent.
• If there is effective viral suppression and good tolerability, Emtricitabine may be continued during pregnancy.
• Dose adjustments in pregnancy are not necessary, as the pharmacokinetics for emtricitabine have not been significantly altered.
• Emtricitabine with tenofovir disoproxil fumarate is a preferred NRTI backbone for initial therapy in antiretroviral-naive pregnant females, HIV/hepatitis B virus-coinfected pregnant females.
• Hepatitis B flare can occur if emtricitabine has been discontinued. Therefore, caution is advised.
• In the event of acute HIV infection during pregnancy, emtricitabine may be prescribed as an initial treatment.
• All HIV-positive females should receive ART during pregnancy to lower their viral load and decrease the chance of perinatal transmission.
• Monitoring is more important during pregnancy than for non-pregnant women.
• All HIV-positive women should continue ART after birth. ART can also be modified once the baby is born.
• Pre-exposure prophylaxis is available for couples with HIV discordance who plan to have a baby.
• Partner with HIV should start therapy one month prior to trying to conceive and continue therapy for one month after.

Emtricitabine use during breastfeeding:

• Breast milk contains Emtricitabine.
• The breast milk concentrations could be higher than the maternal serum.
• Breastfed infants can have emtricitabine detected in their serum.
• As an initial treatment for mothers who are breastfeeding and have HIV-infected, emtricitabine may be used.
• If confirmed, it is important to stop breastfeeding if the infection is serious.
• While waiting for confirmation, milk may be expressed and kept.
• Postnatal HIV transmission can still be a problem even with infant or maternal antiretroviral treatment.
• Some breastfeeding infants have been found to be resistant to multiclass antiviral therapy.
• To reduce HIV transmission in the US, it is best to avoid breastfeeding.

Emtricitabine Dose adjustment in renal disease:

• CrCl ≥50 mL/minute:

  • Dose adjustment is not required.

• CrCl 30 to 49 mL/minute:

  • Capsule: 200 mg every 48 hours.
  • Solution: 120 mg every 24 hours.

• CrCl 15 to 29 mL/minute:

  • Capsule: 200 mg every 72 hours.
  • Solution: 80 mg every 24 hours.

• CrCl <15 mL/minute:

  • Capsule: 200 mg every 96 hours.
  • Solution: 60 mg every 24 hours.

• Hemodialysis:

  • Capsule: 200 mg every 96 hours.
  • Solution: 60 mg every 24 hours.
  • It should be given after hemodialysis on dialysis days (30% removed during 3-hour dialysis)

Emtricitabine Dose adjustment in Liver disease:

There are no dosage adjustments provided in the manufacturer’s labeling; however, not hepatically metabolized, so the impact of hepatic impairment would be minimal. 

Common Side Effects of Emtricitabine:

It is not possible to correlate the frequency of adverse events with emtricitabine alone according to the clinical trials. 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.

• Central Nervous System:

  • Dizziness
  • Headache
  • Insomnia
  • Abnormal Dreams

• Dermatologic:

  • Hyperpigmentation
  • Skin Rash

• Gastrointestinal:

  • Diarrhea
  • Vomiting
  • Nausea
  • Abdominal Pain
  • Gastroenteritis

• Infection:

  • Infection

• Neuromuscular & Skeletal:

  • Weakness
  • Increased Creatine Phosphokinase

• Otic:

  • Otitis Media

• Respiratory:

  • Cough
  • Rhinitis
  • Pneumonia

• Miscellaneous:

  • Fever

Rare Side Effects Of Emtricitabine:

• Central Nervous System:

  • Depression
  • Paresthesia
  • Neuritis
  • Neuropathy

• Endocrine & Metabolic:

  • Increased Serum Triglycerides
  • Increased Amylase
  • Hyperglycemia

• Gastrointestinal:

  • Dyspepsia
  • Increased Serum Lipase

• Genitourinary:

  • Hematuria

• Hematologic & Oncologic:

  • Anemia
  • Neutropenia

• Hepatic:

  • Increased Serum Transaminases
  • Increased Serum Alkaline Phosphatase
  • Increased Serum Bilirubin

• Neuromuscular & Skeletal:

  • Myalgia
  • Arthralgia

• Respiratory:

  • Sinusitis
  • Upper Respiratory Tract Infection
  • Pharyngitis

Contraindications to Emtricitabine:

Hypersensitivity to emtricitabine and any component of the formulation

Warnings and precautions

• Immune reconstitution syndrome:
  • Emtricitabine may cause immune reconstitution syndrome, which is an inflammation response to an indolent, residual opportunistic HIV infection. This can also be seen later in treatment, when further evaluation and treatment are required.

• Hepatomegaly and lactic acidosis:

  • Monotherapy with NRTIs or combined is known to cause severe hepatomegaly and steatosis.
  • Hepatomegaly should not be used in patients who have signs or symptoms of lactic acidosis.

• Chronic hepatitis B

  • Patients with HIV-1 or HBV co-infection and who have discontinued emtricitabine may experience severe acute exacerbations.
  • For co-infections of HIV-1 and HBV, it is necessary to monitor liver function for at least three months after withdrawal emtricitabine.
  • Patients with advanced cirrhosis or hepatic disease should be prescribed anti-hepatitis B therapy. This is because posttreatment exacerbations of hepatitis can lead to liver failure and hepatic decompensation.
  • Patients with HIV must have their HBV status checked before starting therapy.

• Renal impairment

  • Patients with kidney impairment should exercise caution. Sometimes, dose reductions may be necessary.

Emtricitabine: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

HBV testing before starting therapy. Viral load, CD4 Liver function tests Serum creatinine. 

How to administer Emtricitabine?

It should be taken orally with or without food. 

Mechanism of action of Emtricitabine:

It inhibits nucleoside reverse transcriptionase Emtricitabine, a cytosine analog, inhibits viral replication by intracellular phosphorylation emtricitabine-5'-triphosphate to emtricitabine 5. This interferes with HIV viral RNA dependent DNA polymerase. Absorption: Rapid, extensive. Protein binding: <4%. Metabolism:

• Converted to active triphosphate intracellularly, undergoes minimal biotransformation via oxidation and glucuronide conjugation.

Bioavailability:

• Capsule: 93%.
• Solution: 75%.

Note: Relative bioavailability of solution to capsule: 80%. Half-life elimination: Normal renal function:

• Infants, Children, and Adolescents: Elimination half-life (emtricitabine):
  • Single-dose: 11 hours.
  • Multiple-dose: 7.9 to 9.5 hours.
• Adults:
  • Emtricitabine: 10 hours;
  • Intracellular half-life (emtricitabine 5'-triphosphate): 39 hours.

Time to peak plasma concentrations:

• 1 to 2 hours.

Excretion:

• Urine (86% primarily as unchanged drug, 13% as metabolites, 9% of the dose as oxidative metabolite; 4% as glucuronide metabolite);
• feces (14%)

Clearance:

• Renal clearance is greater than creatinine clearance; thus, emtricitabine may be eliminated by both glomerular filtration and active tubular secretion.

International Brands of Emtricitabine:

• Emtriva
• Hui Er Ding
• Landtricib
• Xin Luo Shu

Emtricitabine Brand Names in Pakistan:

No Brands Available in Pakistan.