tenofovir AF

Tenofovir alafenamide (AF) is a medication used in the treatment of chronic hepatitis B virus (HBV) infection in patients 12 years of age or older with compensated liver disease. HBV is spread by body fluids and causes serious liver infection that can lead to liver failure, cirrhosis or cancer. Tenofovir AF is one of the drugs used in antiretroviral treatment (ART) combinations to manage human immunodeficiency virus (HIV) infection that affects the immune system. Neither HBV nor HIV infection can be cured and must be prevented with vaccination and controlled with lifelong medication.

Tenofovir belongs to a class of medications known as nucleoside reverse transcriptase inhibitors (NRTIs), that work by preventing viral replication. Tenofovir AF is a prodrug that enters the liver cells, is converted into tenofovir, and then metabolized into its active form tenofovir diphosphate. Tenofovir diphosphate gets incorporated into the HBV DNA by the HBV reverse transcriptase, the viral enzyme that is essential for replication of the viral DNA, which results in DNA chain termination.

Tenofovir AF is a more recent formulation and different from tenofovir disoproxil fumarate (DF), an earlier formulation. Tenofovir DF is rapidly converted to tenofovir in the blood, while tenofovir AF is more stable in the blood and is converted to tenofovir and its active form only inside the infected liver cells. This property of tenofovir AF makes it possible to maximize tenofovir’s efficacy with lower dosages, improve its safety profile, and reduce the risk of adverse effects on the kidneys and bone mineral density from tenofovir carried in the bloodstream.

• Discontinuation of anti-hepatitis B treatment, including tenofovir AF can result in severe acute exacerbation of hepatitis B. Monitor patients for several months with medical checkups and lab tests after discontinuation of treatment, and resume treatment if required.
• Tenofovir AF is not approved for use as a single agent in the treatment of HIV-1 due to the risk of development of HIV-1 resistance, and its safety and efficacy have not been established in the treatment of patients who are infected with both HBV and HIV-1. Screen HBV patients for HIV-1 infection, and if positive, use an approved combination antiretroviral treatment regimen.
• Tenofovir AF can affect the kidneys, and the risk is higher in patients with impaired kidney function or those taking other drugs that are toxic to the kidneys. Evaluate the patient's kidney function before starting treatment and monitor at regular intervals during treatment. Discontinue tenofovir AF if the patient develops signs and symptoms of kidney damage including decrease in renal function or evidence of Fanconi syndrome.
• Tenofovir AF therapy can lead to lactic acid buildup (lactic acidosis), and enlarged and fatty liver (hepatomegaly with steatosis). Suspend tenofovir AF treatment in patients who develop signs and symptoms of lactic acidosis or significant hepatotoxicity.

Common side effects of tenofovir AF include:

• Headache
• Abdominal pain
• Nausea
• Diarrhea
• Indigestion (dyspepsia)
• Vomiting
• Gas (flatulence)
• Cough
• Reduced bone mineral density
• Fatigue
• Back pain
• Joint pain (arthralgia)
• Rash
• Increase in liver enzymes ALT and AST
• Increase in low-density lipoprotein (LDL) cholesterol
• Excretion of sugar in urine (glycosuria)
• Increase in creatine kinase
• Inflammation of pancreas (pancreatitis)
• Increase in levels of pancreatic enzymes amylase and lipase in blood
• New onset or worsening of kidney function impairment
• Acute exacerbation of hepatitis B with discontinuation of the drug
• Excessive lactic acid buildup in the body (lactic acidosis)
• Liver enlargement with fatty liver (hepatomegaly with steatosis)

Less common side effects of tenofovir AF include:

• Hives (urticaria)
• Swelling beneath the skin and mucous membranes (angioedema)
• Kidney damage including:
  • Acute kidney failure
  • Death of kidney cells (acute tubular necrosis)
  • Proximal renal tubulopathy
  • Fanconi syndrome

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Tablet

• 25 mg

Adult and Pediatric:

Chronic Hepatitis B Infection

Indicated for treatment of chronic hepatitis B virus (HBV) infection in patients aged 12 years or above with compensated liver disease

• Children below 12 years: Safety and efficacy not established
• Adults and children 12 years or above: 25 mg orally once daily with food

Dosage Modifications

Renal impairment

• Mild, moderate, or severe: No dosage adjustment required
• ESRD (creatinine clearance [CrCl] below 15 mL/minute: Not recommended in patients who are not receiving hemodialysis; in patients receiving chronic hemodialysis, administer drug after completion of hemodialysis

Hepatic impairment

• Mild (Child-Pugh A): No dosage adjustment required
• Decompensated (Child-Pugh B or C): Not recommended

Dosing Considerations

• Test for HIV-1 infection before initiating; do not use tenofovir alone in patients coinfected with HIV infection
• Assess serum creatinine, phosphorous, estimated CrCl, urine glucose, and urine protein before initiating and periodically throughout treatment

Overdose

High doses of tenofovir AF can reduce bone mineral density and affect the kidneys. Tenofovir AF overdose may be treated with symptomatic and supportive care, including monitoring of the patient's clinical condition and vital signs.

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation. Tenofovir AF may be removed by hemodialysis efficiently.

• Severe interactions of tenofovir AF include:
  • fezolinetant
• Severe interactions of tenofovir AF include:
  • leniolisib
  • letermovir
  • sotorasib
  • tepotinib
• Tenofovir AF has moderate interactions with at least 25 different drugs.
• Tenofovir AF has no known mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider of all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or health care provider if you have any questions about the medication.

• Animal studies and available data from use of tenofovir AF in pregnant women do not show evidence of fetal harm if administered during pregnancy.
• There is no information on the presence of tenofovir AF or its metabolites in breastmilk, or its effects on milk production and the breastfed infant. Decision to breastfeed should be based on the nursing mother’s clinical need for tenofovir AF, health and developmental benefits of breastfeeding, and the risks to the breastfed infant from exposure to the drug or the mother’s underlying condition.
• There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to VEMLIDY during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258 4263.

• Take tenofovir AF with food exactly as instructed and do not miss your doses, it can result in the development of viral resistance to the medication.
• Do not discontinue tenofovir AF without checking with your physician, it can cause acute, severe exacerbation of hepatitis B.
• If you are co-infected with HIV-1, it must be treated effectively with an approved combination regimen, taking tenofovir alone can increase the risk of development of resistance to HIV medication.
• Report to your physician immediately if you develop new onset or worsening of kidney-related symptoms such as urinary problems, blood in urine or fluid retention.
• Inform your physician if you develop signs and symptoms of liver injury and lactic acidosis such as, dark urine, jaundice, exhaustion, fatigue, exhaustion, nausea, vomiting, muscle cramps or body aches.
• Store tenofovir AF safely out of reach of children.
• In case of overdose, contact your treating physician or Poison Control.