Cabenuva

Indications for Use

Cabenuva is a long-acting injectable treatment for human immunodeficiency virus type 1 (HIV-1). It is a combination of two antiretroviral medications: cabotegravir and rilpivirine. This medication is not a cure for HIV or AIDS, but it helps manage the virus by keeping the viral load low.

Eligibility Criteria

Healthcare providers prescribe Cabenuva to replace a patient's current daily oral HIV medications under specific conditions. To be eligible for this treatment, a person must:

• Be virologically suppressed, meaning their viral load is less than 50 copies of HIV-1 RNA per milliliter of blood.
• Be on a stable antiretroviral regimen.
• Have no history of treatment failure with previous HIV medications.
• Have no known or suspected resistance to either cabotegravir or rilpivirine.

Patient Population

Cabenuva is approved for use in the following groups:

• Adults.
• Adolescents who are at least 12 years old and weigh at least 35 kilograms (about 77 pounds).

Before starting the injections, a healthcare provider may prescribe oral versions of the medications for a short period to ensure the patient tolerates the drugs well before moving to the long-acting injection.

Mechanism of Action

Cabenuva contains two different types of drugs: cabotegravir and rilpivirine. These medications work by blocking specific enzymes that the human immunodeficiency virus (HIV) needs to replicate itself.

How Cabotegravir Works

Cabotegravir is an integrase strand transfer inhibitor (INSTI). It targets an enzyme called integrase, which HIV uses to insert its own genetic material into the DNA of healthy human cells. By blocking this enzyme, the medication prevents the virus from integrating into the host cell, which stops it from making new copies of itself.

How Rilpivirine Works

Rilpivirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). It works by interfering with an enzyme called reverse transcriptase. HIV needs this enzyme to convert its genetic code (RNA) into a form (DNA) that can be used by human cells. When this process is blocked, the virus cannot complete its life cycle.

Combined Effect

By attacking the virus at two different stages, these medications help to:

• Reduce the amount of HIV in the blood (viral load).
• Prevent the virus from damaging the immune system.
• Maintain viral suppression in people who already have an undetectable viral load.

Common Side Effects

The most common side effect reported with Cabenuva is a reaction at the site where the medication was injected. Other common side effects include:

• Pain, swelling, redness, or lumps at the injection site
• Fever
• Tiredness or fatigue
• Headache
• Muscle or bone pain
• Nausea
• Dizziness
• Difficulty sleeping
• Rash

Serious Side Effects

Some side effects can be serious and may require immediate medical care. Contact a healthcare provider if you experience any of the following:

• Severe allergic reactions: Symptoms may include a widespread rash, fever, general ill feeling, extreme tiredness, muscle or joint aches, blisters, or swelling of the face, lips, or mouth.
• Liver problems: Signs of liver damage include yellowing of the skin or eyes, dark-colored urine, light-colored stools, or pain on the right side of the abdomen.
• Mental health changes: New or worsening depression, anxiety, or suicidal thoughts.

Serious Allergic Reactions

Severe hypersensitivity reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported with this medication. Treatment must be discontinued immediately if a rash develops alongside other symptoms such as fever, general malaise, extreme tiredness, muscle or joint aches, blisters, oral lesions, or swelling of the face.

Post-Injection Reactions

Some individuals may experience a reaction within minutes after receiving the injection. These symptoms typically resolve within a few minutes but may include:

• Shortness of breath or breathing difficulties
• Agitation or anxiety
• Abdominal cramping
• Flushing, sweating, or feeling hot
• Numbness in the mouth
• Feeling faint or lightheaded

Liver Health and Monitoring

Liver damage (hepatotoxicity) has occurred in patients receiving this treatment, including those without a history of liver disease. Healthcare providers typically monitor liver enzymes through blood tests before and during treatment. People with a history of Hepatitis B or C may be at an increased risk for liver-related complications.

Depressive Disorders

There is a risk of developing depressive disorders, including suicidal thoughts or behavior. It is important to monitor for changes in mood, feelings of sadness, or hopelessness while using this medication.

Drug Interactions

Cabenuva should not be used with certain other medications because they can significantly lower the levels of the drug in the body, making it less effective. These include certain anti-seizure medications (such as carbamazepine, oxcarbazepine, phenobarbital, or phenytoin), certain antibiotics (such as rifampin, rifabutin, or rifapentine), and the herbal supplement St. John's wort.

Adherence and Resistance

Missing scheduled injection appointments can lead to the virus becoming resistant to the medication. If an injection is missed or delayed, alternative oral medications may be required to maintain viral suppression and prevent the development of resistance.

Pregnancy

There is currently limited data on the use of Cabenuva in pregnant individuals. Because Cabenuva is a long-acting injection, its active ingredients (cabotegravir and rilpivirine) can stay in the system for 12 months or longer after the final dose. This means a fetus could be exposed to the medication even if the injections are discontinued before conception.

Healthcare providers typically discuss the benefits and risks of continuing HIV treatment during pregnancy. There is an Antiretroviral Pregnancy Registry that monitors health outcomes for individuals who take these medications while pregnant. Patients are encouraged to consult their medical team about pregnancy planning and the potential for long-term drug exposure.

Breastfeeding

The Centers for Disease Control and Prevention (CDC) and other health authorities generally recommend that individuals with HIV-1 do not breastfeed their infants. This recommendation is intended to prevent the transmission of HIV to the baby through breast milk. It is also not known if the components of Cabenuva pass into human breast milk, though animal studies suggest they may be present. Because of the risk of virus transmission and the unknown effects of the drug on a nursing infant, breastfeeding is not recommended while using this medication.

Available Forms

Cabenuva is supplied as a kit for intramuscular injection. The kit contains two separate medications in individual vials:

• Cabotegravir extended-release injectable suspension
• Rilpivirine extended-release injectable suspension

The kit includes the vials of medication along with the necessary syringes and needles for administration by a healthcare professional.

FDA Approval History

The U.S. Food and Drug Administration (FDA) first approved Cabenuva in January 2021. It was the first long-acting injectable treatment regimen approved for adults with HIV-1 infection. In 2022, the FDA expanded the approval to include adolescents 12 years of age and older who weigh at least 35 kg.

Approved Indications

Cabenuva is indicated as a complete regimen for the treatment of HIV-1 infection to replace a current stable antiretroviral regimen in individuals who meet specific criteria:

• They are virologically suppressed (HIV-1 RNA less than 50 copies per mL).
• They are on a stable antiretroviral regimen.
• They have no history of treatment failure.
• They have no known or suspected resistance to either cabotegravir or rilpivirine.

Regulatory Status and Dosing

The FDA initially approved Cabenuva for once-monthly administration. In February 2022, the agency approved an additional dosing schedule allowing the medication to be administered every two months. The FDA also updated the labeling to make the oral lead-in period optional, allowing patients to start injections without first taking oral versions of the medication.

There are currently no Boxed Warnings or Risk Evaluation and Mitigation Strategies (REMS) required for Cabenuva.

Factors Influencing Cost

The actual price you pay for Cabenuva can vary based on several elements:

• Insurance Coverage: Your specific health insurance plan, including its formulary and tier system, determines your out-of-pocket costs.
• Treatment Schedule: Cabenuva is administered as an injection either once a month or every two months, which may affect the total cost over time.
• Administration Fees: Because Cabenuva must be administered by a healthcare professional, there may be additional costs associated with the office visit or the injection procedure itself.

Insurance and Government Programs

Most commercial insurance plans, Medicare, and Medicaid provide coverage for Cabenuva. However, some plans may require prior authorization, a process where your doctor must prove the medical necessity of the drug before the insurance company agrees to pay for it.

Financial Assistance

There are programs available to help reduce the cost of Cabenuva for eligible patients:

• Copay Savings: The manufacturer offers a savings program for people with commercial insurance that can help lower monthly out-of-pocket costs.
• Patient Assistance Programs: For those without insurance or with limited coverage, patient assistance programs may provide the medication at no cost to those who meet specific income and eligibility requirements.