Usage
- Emtricitabine + Tenofovir disoproxil fumarate is prescribed for:
- Treatment of HIV-1 infection: Used in combination with other antiretroviral agents in adults and pediatric patients weighing at least 17 kg.
- Pre-exposure prophylaxis (PrEP): Reduces the risk of sexually acquired HIV-1 in at-risk adults and adolescents weighing 35 kg or more, in conjunction with safer sex practices.
- Pharmacological Classification: Nucleoside/Nucleotide Reverse Transcriptase Inhibitor (NRTI/NtRTI)
- Mechanism of Action: These are two nucleoside analog reverse transcriptase inhibitors (NRTIs). They act by inhibiting the reverse transcriptase enzyme, essential for HIV replication. This inhibition disrupts the viral life cycle by interfering with reverse transcription of viral RNA into DNA, thereby blocking integration of the viral genetic material into the host cell’s DNA.
Alternate Names
- Generic Name: Emtricitabine/Tenofovir disoproxil fumarate
- Brand Name: Truvada, and various generics.
How It Works
- Pharmacodynamics: Emtricitabine and Tenofovir are phosphorylated intracellularly to their active metabolites, emtricitabine triphosphate and tenofovir diphosphate. These metabolites compete with natural substrates, resulting in the termination of the DNA chain during reverse transcription, thereby disrupting HIV replication.
- Pharmacokinetics:
- Absorption: Tenofovir disoproxil fumarate is a prodrug rapidly absorbed and hydrolyzed to tenofovir. Bioavailability is increased when taken with food. Emtricitabine is readily absorbed.
- Metabolism: Emtricitabine is minimally metabolized by the liver. Tenofovir disoproxil fumarate is hydrolyzed to its active component, tenofovir.
- Elimination: Both drugs are primarily eliminated renally, both by glomerular filtration and active tubular secretion. Dose adjustments are needed in renal impairment.
- Mode of Action: Both drugs inhibit the activity of the HIV-1 reverse transcriptase enzyme by competing with natural substrates for binding, preventing the synthesis of viral DNA.
- Receptor Binding/Enzyme Inhibition: Competitive inhibition of HIV-1 reverse transcriptase enzyme.
- Elimination Pathways: Primarily renal excretion.
Dosage
Standard Dosage
Adults: One tablet (200 mg emtricitabine/300 mg tenofovir disoproxil fumarate) once daily, with or without food for HIV treatment; with food for PrEP.
Children: For HIV treatment, one appropriately dosed tablet (e.g., 167 mg/250 mg, 133 mg/200 mg, or 100 mg/150 mg) based on weight, once daily in children weighing at least 17 kg. Not recommended for PrEP in children weighing less than 35 kg.
Special Cases:
- Elderly Patients: Monitor renal function. Dosage adjustment may be necessary.
- Patients with Renal Impairment: Dose adjustment is required based on creatinine clearance.
- Patients with Hepatic Dysfunction: No adjustment necessary.
- Patients with Comorbid Conditions: Assess other medications for potential drug interactions and adjust accordingly.
Clinical Use Cases Not indicated for use in specific clinical settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergencies such as status epilepticus or cardiac arrest.
Dosage Adjustments: Reduce the frequency of administration according to creatinine clearance in patients with renal impairment. Not recommended for use in patients with severe renal dysfunction.
Side Effects
Common Side Effects:
Diarrhea, nausea, fatigue, headache, dizziness, trouble sleeping, rash, depression.
Rare but Serious Side Effects:
Lactic acidosis (muscle pain/cramps, unusual tiredness, stomach pain, trouble breathing), hepatotoxicity (jaundice, right upper quadrant pain, loss of appetite), severe allergic reactions (skin rash, itching/hives, swelling of face/tongue/throat), kidney damage (changes in urination, swelling of the ankles/feet/hands), worsening of hepatitis B infection (fatigue, loss of appetite, nausea, jaundice).
Long-Term Effects: Bone loss (osteoporosis, osteomalacia), kidney problems, changes in body fat distribution.
Adverse Drug Reactions (ADR): Lactic acidosis, hepatotoxicity, renal impairment, Stevens-Johnson Syndrome.
Contraindications
- Hypersensitivity to emtricitabine or tenofovir disoproxil fumarate.
- PrEP use in individuals with unknown or positive HIV-1 status.
Drug Interactions
- Antivirals: Didanosine (dose reduction of didanosine recommended or avoid concomitant use), adefovir dipivoxil (avoid concomitant use).
- Other: Drugs eliminated by renal tubular secretion (may increase levels of either interacting drug).
- CYP450 Interactions: No significant interactions.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: B (FDA classification).
- Fetal Risks/Teratogenicity: Minimal risk based on animal studies and limited human data.
- Breastfeeding: Breastfeeding not recommended, although the drug has been detected in human milk in small amounts. If breastfeeding, monitor infant. If replacement feeding is an option, consider formula.
Drug Profile Summary
- Mechanism of Action: Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs), blocking reverse transcription of viral RNA into DNA.
- Side Effects: Common: diarrhea, nausea, headache. Serious: lactic acidosis, hepatotoxicity, renal impairment.
- Contraindications: Hypersensitivity to the components, PrEP in HIV-positive or unknown status.
- Drug Interactions: Didanosine, adefovir dipivoxil, drugs eliminated by renal tubular secretion.
- Pregnancy & Breastfeeding: Pregnancy Category B; breastfeeding not recommended.
- Dosage: 1 tablet (200mg/300mg) daily for adults. Pediatric and renal adjustments apply.
- Monitoring Parameters: Renal function, liver function tests, HIV viral load, CD4 count, hepatitis B serologies (if applicable), bone mineral density.
Popular Combinations
- Used with other antiretrovirals as part of combination antiretroviral therapy (cART)
Precautions
- Test for HIV and hepatitis B before initiating treatment or PrEP.
- Monitor renal function, especially in those with pre-existing renal disease.
- Monitor bone mineral density in long-term use.
- Assess for potential drug interactions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Emtricitabine + Tenofovir disoproxil fumarate?
A: For HIV treatment: One tablet (200 mg/300 mg) once daily for adults and adolescents weighing at least 35 kg. For children weighing 17 kg to less than 35 kg, the dosage depends on body weight. For PrEP: One tablet (200 mg/300 mg) once daily in adults and adolescents weighing at least 35 kg.
Q2: Can it be used during pregnancy?
A: Can be used during pregnancy, but benefits and risks must be considered. Breastfeeding is not recommended.
Q3: How does it work in preventing HIV?
A: It blocks the enzyme reverse transcriptase, preventing the virus from replicating and establishing infection.
Q4: What are the most serious side effects?
A: Lactic acidosis, severe hepatotoxicity, kidney problems, and worsening of Hepatitis B are rare but serious side effects.
Q5: What if I miss a dose?
A: Take the missed dose as soon as you remember, and then continue with your usual dosing schedule. Do not double the dose.
Q6: Does this cure HIV?
A: No. Emtricitabine/tenofovir disoproxil fumarate does not cure HIV or AIDS, but helps manage the infection.
Q7: Can it be taken with food?
A: Yes, it can be taken with or without food for HIV treatment. However, it is recommended to take it with food for PrEP to improve absorption.
Q8: What tests should be done before starting treatment?
A: HIV test, hepatitis B test, and renal function tests should be performed before starting treatment.
Q9: What if I have kidney problems?
A: Dose adjustment or avoidance might be needed. Consult a nephrologist for further evaluation.
Q10: Can I drink alcohol while taking this medication?
A: Alcohol is not known to directly interact with it, but excessive alcohol can damage the liver and kidneys, which may exacerbate the medication’s side effects. Moderate alcohol consumption might be acceptable, but discuss this with your doctor.
