Tenofovir alafenamide (Vemlidy) is an inactive compound that is converted inside the cells to the active compound tenofovir diphosphate. It is used to treat adult patients with compensated chronic liver disease and active chronic hepatitis B virus (HBV) infection.

Tenofovir alafenamide Dose in Adults

Dose in the treatment of chronic hepatitis B:

• 25 mg orally once a day

Tenofovir alafenamide Dose in Children

Tenofovir alafenamide dose in children:

• Weight less than 25 kgs:

  • Not recommended

• Weight 25 - 35 Kgs:

  • 25 mg once a day.

• Weight more than 35 kgs:

  • 25 mg once daily

Tenofovir pregnancy Risk Category: B

• Its use in pregnancy is not known. Tenofovir alafenamide doesn't cross the placenta easily.
• Some studies have shown an increased risk of stillbirth and low birth weight in infants under gestational age.
• Maternal ART is a beneficial treatment that has clear benefits. However, it should not be stopped because of concerns about adverse neonatal outcomes.
• All infants who have been exposed to antiretroviral medication should be followed up for a long time.
• Children with significant organ system abnormalities (especially the heart or CNS) that are not of known etiology should be examined for possible mitochondrial dysfunction.
• NRTIs have been shown to cause lactic acidosis, hepatic steatosis, and other symptoms related to mitochondrial toxicity.
• Nucleoside reverse transcriptase inhibits are generally well tolerated, and the benefits outweigh any potential risks.
• Females who become pregnant while taking Tenofovir Alafenamide may continue to take the drug if they are well tolerated and effective in controlling their viral infection.
• The pharmacokinetics of tenofovir-alafenamide are not affected by pregnancy. Dose adjustments are not necessary.
• Females coinfected with HIV and HBV who are taking tenofovir alafenamide before pregnancy and are virally suppressed should be offered a choice to switch to tenofovir disoproxil fumarate or continue with the current regimen.
• ART is generally used to treat HIV-positive pregnant women. It keeps the virus load under the limit of detection and lowers the chance of perinatal transmission.
• Monitoring during pregnancy is more common than monitoring in adults who are not pregnant.
• All females with HIV should continue receiving antiretroviral treatment after giving birth.

Use of Tenofovir alafenamide during breastfeeding

• It is unknown if tenofovir alafenamide can be found in breast milk.
• Breastfeeding is safe for women with hepatitis A. However, breastfeeding is not advised for those whose nipples are cracked/bleeding.
• The risk of HIV transmission after birth does not disappear with an infant or maternal antiretroviral treatment.
• A multiclass-resistant virus was also detected in breastfed infants, despite maternal therapy.
• To reduce the possibility of HIV transmission, pregnant women with HIV should not breastfeed in the United States. This is because formula milk is readily available, affordable, safe, and reliable.

Tenofovir alafenamide Dose in Renal Disease:

• CrCl ≥15 mL/minute:

  • Adjustment in the dose is not required.

• CrCl <15 mL/minute:

  • Avoid its use.

• ESRD requiring hemodialysis:

  • Adjustment in the dose is not required.
  • Administer the dose after dialysis on hemodialysis days.

Tenofovir alafenamide Dose in liver Disease:

• Mild impairment (Child-Pugh class A):

  • Adjustment in the dose is not required.

• Decompensated cirrhosis (Child-Pugh class B or C):

  • Avoid its use.

Common Side Effects of Tenofovir alafenamide Include:

• Central Nervous System:

  • Headache

• Neuromuscular & Skeletal:

  • Decreased Bone Mineral Density

Less Common Side Effects of Tenofovir Alafenamide Include:

• Cardiovascular:

  • Increased Serum Creatine Kinase

• Central Nervous System:

  • Fatigue

• Dermatologic:

  • Skin Rash

• Endocrine & Metabolic:

  • Increased LDL Cholesterol
  • Glycosuria
  • Increased Amylase

• Gastrointestinal:

  • Abdominal Pain
  • Nausea
  • Diarrhea
  • Dyspepsia
  • Flatulence
  • Vomiting

• Hepatic:

  • Increased Serum Alanine Aminotransferase
  • Increased Serum Aspartate Aminotransferase

• Neuromuscular & Skeletal:

  • Back Pain
  • Arthralgia

• Respiratory:

  • Cough

Contraindication to Tenofovir alafenamide (Vemlidy) Include:

• Severe allergic reactions, whether to tenofovir alafenamide and/or any part of this formulation

Warnings and precautions

• Hepatomegaly and lactic acidosis:

  • With the combination of antiretrovirals and nucleoside analogs, there have been cases of steatosis that include fatal lactic acidosis and massive hepatomegaly.
  • If the patient experiences significant hepatotoxicity, such as jaundice, hypochondriac pain right and marked elevations in liver enzymes, treatment must be stopped.
  • If the patient develops lactic acidosis, treatment should be stopped immediately.

• Hepatic impairment

  • Patients with Child-Pugh class C or B hepatic impairment shouldn't be given the drug.

• Hepatitis B acute exacerbation [US Boxed Warn]

  • Hepatitis B treatment may be stopped if severe complications occur.
  • For several months, it is important to monitor clinical and laboratory data.
  • If there is suspicion of reactivation, treatment may be restarted.

• HIV-1 and HBV co-infection

  • Monotherapy should not be recommended for HIV-1 patients because of the possibility of resistance.

• Renal impairment

  • Tenofovir alafenamide should not be administered to patients with pre-existing kidney impairment (CrCl less than 15ml/min) or hemodialysis.

• Toxicity in the renal system:

  • It has been associated with Fanconi syndrome and acute renal failure.
  • Preexisting renal impairment, patients taking nephrotoxic drugs like NSAIDs, and patients at high risk for developing renal toxicity are two examples of those who are most at risk.
  • Before and during treatment, it is important to check the serum creatinine.
  • Patients should have their serum creatinine, estimated CrCl, urine protein, and glucose monitored as soon as they are clinically advised.
  • Patients with Fanconi syndrome or significant renal dysfunction should be advised not to continue treatment.

Tenofovir alafenamide: Drug Interaction

Monitor:

• Serum creatinine
• serum phosphorus (in patients with chronic kidney disease)
• urine glucose
• urine protein (before the initiation of therapy and as clinically indicated during therapy)
• HIV testing (prior to initiation)
• Liver function tests
• Following the discontinuation of therapy, patients' clinical and laboratory data should be monitored for several months.

How to administer Tenofovir alafenamide (Vemlidy)?

• Administer orally with food.

Mechanism of action of Tenofovir alafenamide (Vemlidy):

• It is an analog to adenosine 5’-monophosphate.
• This is converted intracellularly to tenofovir by hydrolysis and then phosphorylated into the active compound, tenofovir.
• The active moiety blocks the replication of the hepatitis A virus by inhibiting HBV polymerase.

Protein binding:

• 80% of the drug is bound to plasma proteins.

Metabolism:

• Intracellularly, it is converted to tenofovir and then phosphorylated to the active tenofovir diphosphate.

Bioavailability:

• It Increases by about 65% with a high-fat meal

Half-life elimination:

• 0.51 hours

Time to peak, serum:

• 0.48 hours

Excretion:

• Via Feces (31.7%) and urine (<1%)

International Brands of Tenofovir alafenamide:

• Tafecta
• Telabee
• Vemlidy

Tenofovir alafenamide Brands in Pakistan:

It is not available in Pakistan.