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

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)