Tenofovir alafenamide

Chronic Hepatitis B

Tenofovir alafenamide is used to treat chronic hepatitis B virus (HBV) infection in adults and children 6 years of age and older who weigh at least 55 pounds (25 kg). It is typically prescribed for patients with compensated liver disease, which means the liver is still functioning well despite the infection.

HIV-1 Treatment

This medication is also used as part of a combination therapy to treat human immunodeficiency virus type 1 (HIV-1). It is never used alone for HIV treatment; it must be taken with other antiviral medications to help control the virus and support the immune system.

HIV-1 Prevention (PrEP)

In specific combination products, tenofovir alafenamide is used for pre-exposure prophylaxis (PrEP). This is intended to reduce the risk of HIV-1 infection in individuals who are at high risk of acquiring the virus through sexual contact.

Important Considerations

• Not a cure: This medication does not cure hepatitis B or HIV. It works by lowering the amount of virus in the body to help manage the condition.
• Transmission: Taking this drug does not prevent the spread of HBV or HIV to others through sexual contact or exposure to blood.
• Long-term management: It is used for long-term treatment to help prevent complications of chronic infection, such as liver damage or immune system failure.

Mechanism of Action

Tenofovir alafenamide belongs to a class of drugs known as nucleoside reverse transcriptase inhibitors (NRTIs). It is a prodrug, which means it is converted into its active form, tenofovir, after it enters the body's cells.

The medication works by interfering with the way the virus replicates through the following steps:

• Blocking Enzymes: It inhibits specific enzymes that the virus needs to make copies of its genetic material. For hepatitis B, it targets the viral DNA polymerase, and for HIV, it targets reverse transcriptase.
• Stopping DNA Synthesis: The drug mimics the natural building blocks of viral DNA. When the virus attempts to use the drug to build new DNA, the process is interrupted, preventing the virus from creating complete copies of itself.
• Reducing Viral Load: By stopping the virus from multiplying, the medication reduces the total amount of the virus in the body (the viral load).

While tenofovir alafenamide helps control the infection and can reduce the risk of liver damage in hepatitis B patients, it is not a cure. It does not eliminate the virus from the body or prevent the spread of the virus to others through blood or sexual contact.

Common Side Effects

The most frequently reported side effects of tenofovir alafenamide include:

• Headache
• Nausea
• Cough
• Back pain
• Feeling tired or weak
• Stomach pain
• Joint pain

Serious Side Effects

Seek medical attention immediately if you experience any of the following serious symptoms:

• Liver problems: Symptoms may include yellowing of the skin or the whites of the eyes, dark-colored urine, light-colored stools, loss of appetite, or pain in the upper right side of the stomach.
• Lactic acidosis: This is a serious medical emergency characterized by unusual muscle pain, trouble breathing, stomach pain with nausea and vomiting, feeling cold (especially in the arms and legs), dizziness, or a fast or irregular heartbeat.
• Kidney problems: New or worsening kidney impairment, which may include changes in urination.
• Bone issues: Bone pain or thinning of the bones (osteoporosis), which may increase the risk of fractures.
• Immune system changes: A condition called immune reconstitution syndrome can occur, where the immune system reacts to previous infections that were hidden in the body.

Hepatitis B Exacerbation

Discontinuing tenofovir alafenamide may cause a severe worsening of hepatitis B infection. Monitoring of liver function through blood tests is typically required for several months after the medication is stopped to check for signs of liver damage.

HIV Resistance

Using this medication in patients with unrecognized or untreated HIV-1 infection can lead to the virus developing resistance to certain treatments. HIV testing is recommended before starting therapy to ensure the appropriate treatment regimen is used.

Lactic Acidosis and Liver Issues

A serious condition called lactic acidosis, where too much acid builds up in the blood, has been reported with this class of drugs. Additionally, severe liver problems such as an enlarged liver or fatty liver may occur. These conditions can be life-threatening and require immediate medical attention if symptoms like unusual fatigue, stomach pain, or yellowing of the skin occur.

Kidney and Bone Effects

• Kidney Impairment: This drug may cause new or worsening kidney problems, including kidney failure. Regular monitoring of kidney function is often necessary during treatment.
• Bone Density Loss: A decrease in bone mineral density has been observed in some patients. This may increase the risk of fractures, particularly in those with a history of bone issues or osteoporosis.

Immune Reconstitution Syndrome

In patients with HIV, the immune system may become more active after starting treatment. This can cause the body to develop an inflammatory response to previous or hidden infections, such as pneumonia or tuberculosis, as the immune system recovers.

Pregnancy

Data on the use of tenofovir alafenamide in pregnant women are limited. While animal studies have not shown evidence of harm to the fetus, there is not enough human information to determine if it is completely safe. If you are pregnant or planning to become pregnant, talk to your doctor about the potential risks and benefits of continuing this medication.

For individuals with HIV, it is important to maintain an undetectable viral load during pregnancy to prevent transmission to the baby. Your healthcare provider will help determine the best treatment plan for your specific situation.

Breastfeeding

It is not known whether tenofovir alafenamide passes into human breast milk. Because of the risk of transmitting HIV to the infant through breast milk and the potential for side effects in the baby, healthcare providers generally recommend that individuals with HIV do not breastfeed.

If you are taking this medication for chronic hepatitis B, consult your healthcare team to discuss the risks and benefits of breastfeeding while on this treatment.

Dosage Forms

Tenofovir alafenamide is available as a tablet for oral administration. It is provided in the following formats:

• Oral Tablet: A standalone medication containing only tenofovir alafenamide as the active ingredient.
• Combination Oral Tablet: A single tablet that combines tenofovir alafenamide with other antiviral medications.

These tablets are designed to be swallowed whole. The choice of formulation depends on whether the medication is being used to treat chronic hepatitis B or as part of a treatment regimen for HIV-1 infection.

FDA Approval Status

Tenofovir alafenamide was first approved by the U.S. Food and Drug Administration (FDA) in 2016. It is indicated for the treatment of chronic hepatitis B virus (HBV) infection in adults and pediatric patients 6 years of age and older who weigh at least 25 kg and have compensated liver disease.

In addition to its use as a standalone treatment for hepatitis B, tenofovir alafenamide is approved as an active ingredient in various fixed-dose combination tablets for the treatment of HIV-1 infection and, in specific combinations, for HIV-1 pre-exposure prophylaxis (PrEP).

Boxed Warning

The FDA-approved labeling for tenofovir alafenamide includes a boxed warning regarding the risk of severe acute exacerbations of hepatitis B. Patients with HBV who discontinue treatment may experience a sudden and severe worsening of their condition. Healthcare providers typically monitor hepatic function closely for several months after the medication is stopped.

Regulatory Considerations

Before starting treatment, patients are typically screened for HIV-1 infection. Tenofovir alafenamide should not be used alone in patients with unrecognized or untreated HIV-1 infection, as this may lead to the development of drug resistance.

Role in HIV Management

Tenofovir alafenamide belongs to a group of medicines called nucleoside reverse transcriptase inhibitors (NRTIs). In the treatment of HIV-1, it is used to decrease the amount of virus in the blood and increase the number of immune cells that help fight infections. While it helps manage the condition and may reduce the risk of transmitting the virus to others, it is not a cure for HIV or AIDS.

Combination Requirements

For HIV treatment, tenofovir alafenamide must be used with at least one other antiretroviral medication. It is frequently provided in a single pill that combines multiple drugs to simplify the treatment regimen and prevent the virus from becoming resistant to the medication.

Usage and Monitoring

• Testing: Healthcare providers typically test patients for Hepatitis B (HBV) before starting this medication, as it is also used to treat HBV.
• Consistency: To be effective, the medication must be taken consistently. Missing doses can allow the virus to multiply and develop resistance.
• Long-term health: Compared to older versions of tenofovir, this form is designed to be effective at lower doses, which may reduce the impact on bone density and kidney function.