Truvada (Tenofovir disoproxil fumarate and Emtricitabine)

Truvada is a fixed-dose combination of two antiviral drugs Tenofovir disoproxil fumarate and emtricitabine. It is used in the treatment of HIV infection and for PREP (pre-exposure prophylaxis in high-risk individuals.

Truvada (Tenofovir disoproxil fumarate and emtricitabine) Uses:

  • Treatment of HIV-1 infection:

    • It is used in treatment of HIV-1 infection in combination with other antiretroviral agents in adults and pediatric patients weighing ≥17 kg.
  • HIV-1 infection, pre-exposure prophylaxis:

    • It is indicated in preexposure prophylaxis to reduce the risk of sexually acquired HIV-1 infection in at-risk adults and adolescents weighing ≥35 kg, in combination with safer sex practices.
  • Off Label Use of Tenofovir disoproxil fumarate and emtricitabine in Adults:

    • It is used in :
      • Hepatitis B (antiviral-resistant)
      • HIV/Hepatitis B coinfection
      • HIV-1 nonoccupational post-exposure prophylaxis
      • HIV-1 occupational post-exposure prophylaxis
      • HIV-1 infection
      • preexposure prophylaxis in injecting drug users (IDU)

Truvada (Tenofovir disoproxil fumarate and emtricitabine) dose in adults:

Truvada Treatment dose of HIV-1 infection:

  • One tablet (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) per oral  once daily given in combination with other antiretroviral agents.

Truvada Dose in preexposure prophylaxis of HIV-1 infection (PrEP) in uninfected high-risk individuals:

  • One tablet (emtricitabine 200 mg/tenofovir 300 mg disoproxil fumarate) per oral once daily given.

Truvada treatment dose of HIV-1 infection, PrEP in injecting drug users (IDU) (off-label):

  • One tablet (emtricitabine 200 mg/tenofovir 300 mg disoproxil fumarate) per oral once daily given.

Truvada dose in the treatment of HIV-1/Hepatitis B co-infection (off-label):

  • One tablet (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) per oral once daily given in combination with other antiretroviral agents.

Truvada dose in the treatment of HIV-1 nonoccupational postexposure prophylaxis (off-label):

  • One tablet (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg) per oral once daily given for 28 days in combination with other antiretroviral agents.
  • Therapy should be started within 72 hours of exposure.

Truvada dose in the prophylaxis of HIV-1 occupational postexposure (off-label):

  • One tablet (emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg)per oral once daily given  for 4 weeks with concomitant raltegravir.
  • Start therapy as soon as possible after occupational exposure (and within 72 hours).

Truvada (Tenofovir disoproxil fumarate and emtricitabine) dose in children:

Truvada dose in the treatment of HIV-1 infection:

  • Use in combination with other antiretroviral agents.
  • Multiple tablet strengths exist and contains different amounts of emtricitabine and tenofovir.
  • Children and Adolescents weighing ≥17 kg and who are able to swallow a tablet whole:
    • <17 kg:

      • Not recommended for use.
      • This product is a fixed-dose combination.
    • 17 to <22 kg:

      • One tablet (emtricitabine 100 mg/tenofovir 150 mg) per oral once daily given.
    • 22 to <28 kg:

      • One tablet (emtricitabine 133 mg/tenofovir 200 mg)per oral once daily given.
    • 28 to <35 kg:

      • One tablet (emtricitabine 167 mg/tenofovir 250 mg) per oral once daily given.
    • ≥35 kg:

      • One tablet (emtricitabine 200 mg/tenofovir 300 mg) per oral once daily given.

Truvada Dose in the occupational Postexposure prophylaxis:

  • Adolescents:
    • One tablet (emtricitabine 200 mg/tenofovir 300 mg)per oral once daily given for 28 days in combination with other antiretroviral agents.
    • Start therapy within 72 hours of exposure.

Truvada Dose in the Preexposure prophylaxis of (PrEP) in uninfected high-risk individuals:

  • Adolescents weighing ≥35 kg:
    • One tablet (emtricitabine 200 mg/tenofovir 300 mg)per oral once-daily given
    • Patients should be screened for HIV infection before initiation of therapy and at least once every 3 months; adherence should also be closely monitored.

Truvada Pregnancy Risk Category: B

  • The Health and Human Services Perinatal HIV Guidelines recommend that pregnant women who are antiretroviral-naive and receive emtricitabine and tenofovir dioproxil fumarate as their first-line treatment.
  • As part of treatment for acute HIV infection during pregnancy, emtricitabine can be combined with tenofovir dioproxil fumarate.
  • It is the preferred therapy for HIV-infected women who have received antiretroviral treatment before and are starting it again.
  • If there is good viral suppression and tolerance, therapy can be continued throughout pregnancy.
  • The HHS perinatal guidelines recommend this treatment for patients who have co-infections with HIV and hepatitis B viruses during pregnancy.
  • Pre-exposure prophylaxis for couples with discordant HIV is recommended for patients planning to conceive.
  • In partners with HIV-negative HIV infections, therapy should be initiated 1 month prior to conception and continued for one month thereafter.

Use of tenofovir disoproxil fuarate and emtricitabine during breastfeeding

  • Breast milk contains tenofovir and emtricitabine.
  • Pre-exposure prophylaxis is not contraindicated by breastfeeding.

Truvada Dose adjustment in renal disease:

  • Treatment of HIV-1 infection:

    • Manufacturer's labeling:

      • CrCl ≥50 mL/minute:

        • No dosage adjustment is necessary.
      • CrCl 30 to 49 mL/minute:

        • Increase interval to every 48 hours.
      • CrCl <30 mL/minute:

        • Not advised.
      • Hemodialysis:

        • Not advised.
    • Alternate recommendations:

      • CrCl <50 mL/minute (and not on hemodialysis) or GFR <60 mL/minute/1.73 m²:

        • Avoid usage of tenofovir
    • Pre-exposure Prophylaxis:

      • CrCl ≥60 mL/minute:

        • No dosage adjustment is necessary.
      • CrCl <60 mL/minute:

        • Not recommended.

Truvada Dose adjustment in liver disease:

  • There are no dosage adjustments given in the manufacturer's labeling

Common Side Effects of Truvada (Tenofovir disoproxil fumarate and emtricitabine):

  • Neuromuscular & skeletal:

    • Decreased bone mineral density.

Uncommon Side Effects of Truvada (Tenofovir disoproxil fumarate and emtricitabine):

  • Central Nervous System:

    • Headache
  • Endocrine & Metabolic:

    • Weight Loss
  • Gastrointestinal:

    • Abdominal Pain
  • Hematologic & Oncologic:

    • Abnormal Phosphorus Levels
    • Decreased Neutrophils
  • Neuromuscular & Skeletal:

    • Bone Fracture

Contraindications to Truvada (Tenofovir disoproxil fumarate and emtricitabine):

  • Hypersensitivity to tenofovir, emtricitabine or any other part of the formulation.
  • Patients with HIV-1 or unknown status should be protected from exposure.

Warnings and precautions

  • Reduced bone mineral density

    • Tenofovir disoproxil fumarate is shown to cause a reduction in bone mineral density and increased bone metabolism markers in HIV-1-infected children and adults.
    • Patients with an underlying history of osteoporosis or pathologic fractures should be monitored for their bone mineral density.
    • As it may be beneficial, all patients should receive vitamin D and calcium supplementation.
    • It is not known if long-term bone health or fracture risk will be.
    • Any abnormalities require expert evaluation.
  • Immune reconstitution syndrome:

    • An immune reconstitution syndrome is an inflammation response to a residual HIV infection.
    • This can also be caused by activation of autoimmune disorders such as Graves' disease or polymysitis. Treatment will include further evaluation and treatment.
  • Hepatomegaly and lactic acidosis:

    • The combination of nucleoside analogs can lead to fatal lactic acidosis, severe hepatomegaly and severe steatosis.
    • Transaminitis and signs or symptoms of lactic acidosis should be treated immediately.
  • Osteomalacia, renal dysfunction

    • Therapy can lead to osteomalacia, which is a condition that causes bone pain, fractures and weakness.
    • Patients at high risk of renal dysfunction should look out for signs such as osteomalacia and hypophosphatemia.
  • Toxicity in the renal system:

    • Therapy can cause renal toxicity, including acute renal failure or Fanconi syndrome.
    • High doses of tenofovir or multiple NSAID therapies are risk factors for kidney impairment. It should therefore be avoided.
    • Patients taking tenofovir disoproxil fumarate and at high risk of renal impairment should consider other NSAIDs as analgesics.
    • Monitoring creatinine, creatinine clearance and urine glucose is essential before and during therapy.
    • Patients with chronic kidney disease should have their serum phosphorus checked.
    • An alarming decrease in GFR in HIV patients (a decrease of >25% from baseline and to a level below 60 mL/minute/1.73m2) is indicative of proximal tubular dysfunction (eg euglycemic glucoseuria, increased urinary Phosphorus excretion and hypophosphatemia and proteinuria). Tenofovir should be discontinued and replaced with other antivirals.
  • Chronic Hepatitis B: [US-Boxed Warning]

    • Stopping antiviral therapy may cause severe HBV symptoms in HBV-infected people.
    • Patients infected by HBV should be monitored for signs and symptoms, as well as hepatic function monitoring, for several months.
    • In the case of advanced liver disease or cirrhosis,anti-hepatitis B therapy might be needed.
    • All HIV-positive patients should have HBV testing done before starting treatment.
    • Patients who are HBV-uninfected should receive vaccination.
  • Comprehensive prevention program:

    • Pre-exposure prophylaxis should include a comprehensive HIV-1 prevention program, including access to condoms, risk reduction counseling, and medication adherence.
    • Regular monitoring is also necessary (eg, HIV status for patient and partner(s), risk behaviour, adherence, adverse effect, HIV-1 transmission through sexually transmitted infection)
  • HIV treatment and renal impairment

    • Patients with severe renal impairment (CrCl 50mL/minute) will need to reduce their dose.
    • It is not recommended for patients with CrCl less than 30 mL/minute or hemodialysis.
    • Preexisting kidney disease is more likely in HIV patients who are taking tenofovir (CrCl 50 mL/minute, not on hemodialysis or GFR 60 mL/minute/1.73 m). Therefore, alternate treatments should be considered.
  • PrEP and renal impairment

    • CrCl below 60 mL/minute is not recommended.
  • Resistance risk with PrEP [US Boxed Warning]

    • HIV-1 status must be confirmed prior to and at minimum every 3 months during treatment.
    • PrEP should not ever be administered to anyone with signs or symptoms of an acute HIV-1 infection unless HIV-1 status has been confirmed by a test approved and approved by FDA. This is done in order to detect HIV-1 infection (acute or primary).
    • The risk of developing drug-resistant HIV-1 variants is higher if an acute HIV infection is not detected.
    • Some HIV-1 tests, such as rapid tests, cannot detect acute HIV-1 infection.
    • It is important to screen for potential exposure events and acute viral infections within four weeks of beginning PrEP.
    • In the event of an infection, therapy should be delayed for four weeks. HIV-1 status should also be checked.
    • HIV-1 PrEP regimen should change to HIV-1 treatment regimen in the event of HIV-1 screening results indicating possible HIV-1 infection. If symptoms of acute HIV-1 infections develop following exposure, this should be continued until a negative diagnosis is made.

Tenofovir disoproxil fumarate and emtricitabine: Drug Interaction

Risk Factor C (Monitor therapy)

Acyclovir-Valacyclovir

May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Acyclovir-Valacyclovir.

Aminoglycosides

May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides.

Cabozantinib

MRP2 Inhibitors may increase the serum concentration of Cabozantinib.

Cidofovir

May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Cidofovir.

Cobicistat

May enhance the adverse/toxic effect of Tenofovir Products. More specifically, cobicistat may impair proper tenofovir monitoring and dosing.

Darunavir

Tenofovir Disoproxil Fumarate may increase the serum concentration of Darunavir. Darunavir may increase the serum concentration of Tenofovir Disoproxil Fumarate.

Ganciclovir-Valganciclovir

Tenofovir Products may increase the serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase the serum concentration of Tenofovir Products.

Lopinavir

May enhance the nephrotoxic effect of Tenofovir Disoproxil Fumarate. Lopinavir may increase the serum concentration of Tenofovir Disoproxil Fumarate.

Orlistat

May decrease the serum concentration of Antiretroviral Agents.

Simeprevir

Tenofovir Disoproxil Fumarate may decrease the serum concentration of Simeprevir. Simeprevir may increase the serum concentration of Tenofovir Disoproxil Fumarate.

Tipranavir

Tenofovir Disoproxil Fumarate may decrease the serum concentration of Tipranavir. Tipranavir may decrease the serum concentration of Tenofovir Disoproxil Fumarate.

Velpatasvir

May increase the serum concentration of Tenofovir Disoproxil Fumarate.

Voxilaprevir

Tenofovir Disoproxil Fumarate may increase the serum concentration of Voxilaprevir.

Risk Factor D (Consider therapy modification)

Atazanavir

Tenofovir Disoproxil Fumarate may decrease the serum concentration of Atazanavir. Atazanavir may increase the serum concentration of Tenofovir Disoproxil Fumarate. Management: Must use boosted atazanavir in adults; give combo (atazanavir/ritonavir or atazanavir/cobicistat with tenofovir) as a single daily dose with food. Pediatric patients, pregnant patients, and users of H2-blockers require other dose changes.

Diclofenac (Systemic)

May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to this combination whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose.

Ledipasvir

May increase the serum concentration of Tenofovir Disoproxil Fumarate. Management: Avoidance of this combination is recommended under some circumstances. Refer to full monograph for details.

Nonsteroidal Anti-Inflammatory Agents

May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose.

Risk Factor X (Avoid combination)

Adefovir

May diminish the therapeutic effect of Tenofovir Products. Adefovir may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Adefovir.

Cladribine

Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine.

Didanosine

Tenofovir Disoproxil Fumarate may diminish the therapeutic effect of Didanosine. Tenofovir Disoproxil Fumarate may increase the serum concentration of Didanosine. Management: Avoid concomitant treatment with tenofovir disoproxil fumarate and didanosine. Consider altering even existing, stable treatment to avoid this combination.

LamiVUDine

May enhance the adverse/toxic effect of Emtricitabine.

Monitoring parameters:

  • CBC with differential
  • reticulocyte count
  • creatine kinase
  • CD4 count
  • HIV RNA plasma levels
  • serum phosphorus
  • serum creatinine
  • urine glucose and urine protein (prior to initiation and as clinically indicated during therapy)
  • hepatic function tests
  • bone density (patients with a history of bone fracture or have risk factors for bone loss);
  • testing for HBV is recommended prior to the initiation of antiretroviral therapy; weight (children).
  • Patients with HIV and HBV coinfection should be monitored for several months following tenofovir discontinuation.

HIV-1 preexposure prophylaxis (PrEP)

  • Pregnancy test(every visit)
  • BUN and serum creatinine (prior to initiation, 3 months after initiation, then every 6 months).
  • serum phosphorus in patients with chronic kidney disease, testing for HBV (prior to initiation).
  • STIs (prior to initiation, then at least every 6 months, even if asymptomatic)
  • Documented negative HIV test (immediately prior to use, every 2-3 months, and following discontinuation of PrEP),
  • Assess risk behaviors and symptoms of sexually-transmitted infections (STIs) or acute HIV-1 infection and provide condoms (immediately prior to use, then every 2-3 months during therapy)
  • Urine glucose and urine protein (in patients at risk for renal impairment or who experienced renal impairment while taking adefovir)

HIV occupational post-exposure prophylaxis (PEP)

  • CBC LFTs at baseline and 2 weeks after exposure (minimum recommendations, others dictated by clinical assessment)
  • RFTs
  • Documented HIV test (at baseline and 6 weeks, 12 weeks and 6 months after exposure)
  • if confirmation that a fourth-generation HIV p2 antigen-HIV antibody test is being used, monitor at baseline, 6 weeks, and 4 months after exposure.

How to administer Truvada (Tenofovir disoproxil fumarate and emtricitabine):

Can be taken orally with or without food.

Mechanism of action of Truvada (Tenofovir disoproxil fumarate and emtricitabine):

 

  • Combination of nucleoside and nucleotide retranscriptase inhibitors
  • Emtricitabine can be used as a cytosine analogue, while tenofovir can be used as an analog to adenosine 5’-monophosphate.
  • Viral replication inhibition is achieved by each drug interfering in HIV viral RNA dependent DNA Polymerase.

Refer to the individual monographs.

International Brands of Tenofovir disoproxil fumarate and emtricitabine:

  • Agifovir-E
  • Emtifovir
  • Emzavir
  • Fovirem
  • Recovir-Em
  • Teno-Em
  • TenofEm
  • Tenofence Plus
  • Tenvir EM
  • Tenvir-EM
  • Tenvor-Em
  • Tolak E
  • Trenstad
  • Truvada

Tenofovir disoproxil fumarate and emtricitabine Brands in Pakistan:

Truvada (Gilead Sciences)

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