berotralstat

Hereditary Angioedema Prevention

Berotralstat is used for the routine prevention of hereditary angioedema (HAE) attacks. HAE is a rare genetic condition that causes episodes of severe swelling in various parts of the body, including the hands, feet, face, airway, or digestive tract. By taking this medication daily, patients aim to reduce the frequency and severity of these swelling episodes.

This medication is approved for use in:

• Adults
• Children 12 years of age and older

Limitations of Use

It is important to understand the specific role of berotralstat in managing HAE:

• Not for acute treatment: Berotralstat is a preventive (prophylactic) medicine. It should not be used to treat an acute HAE attack that has already started, as it does not work quickly enough to provide immediate relief for sudden swelling.
• Rescue medication: Healthcare providers typically advise patients to continue having access to rescue medications specifically designed to treat acute attacks while they are on a preventive regimen of berotralstat.

Mechanism of Action

Berotralstat belongs to a class of medications called plasma kallikrein inhibitors. It is used for the routine prevention of attacks of hereditary angioedema (HAE), a genetic condition that causes episodes of severe swelling in various parts of the body.

How it Prevents Swelling

In people with HAE, a substance in the blood called bradykinin is produced in excessive amounts. Bradykinin causes blood vessels to widen and leak fluid into surrounding tissues, which results in the characteristic swelling and pain of an HAE attack.

Berotralstat works by targeting the biological pathway that creates bradykinin:

• Inhibiting Plasma Kallikrein: The medication binds to plasma kallikrein, which is an enzyme (a type of protein) responsible for releasing bradykinin.
• Lowering Bradykinin Levels: By blocking the activity of plasma kallikrein, berotralstat reduces the overall production of bradykinin in the body.
• Preventing Inflammation: With less bradykinin circulating, blood vessels are less likely to leak, which helps prevent the onset of swelling episodes.

Because berotralstat works by maintaining a steady level of enzyme inhibition, it is taken daily to provide ongoing protection. It is important to note that this medication is a preventive treatment and is not intended to treat an acute HAE attack once it has already started.

Common Side Effects

Many people taking berotralstat experience mild side effects. The most common include:

• Abdominal pain
• Vomiting
• Diarrhea
• Heartburn or indigestion
• Back pain

Serious Side Effects

Contact a healthcare provider immediately if you experience any of the following serious symptoms:

• Signs of a severe allergic reaction, such as rash, hives, or swelling of the face, tongue, or throat
• Difficulty breathing or swallowing
• Changes in heart rhythm, such as a fast, pounding, or irregular heartbeat
• Severe dizziness or fainting

This medication may cause changes in the electrical activity of the heart (QT prolongation), especially if taken at higher than recommended doses. It is important to follow the prescribed dosage exactly and report any new or worsening symptoms to your doctor.

Acute HAE Attacks

Berotralstat is intended for the prevention of hereditary angioedema (HAE) attacks and should not be used to treat an acute attack. Patients should have access to an approved rescue medication for the treatment of sudden swelling episodes.

Heart Rhythm Concerns

Doses of berotralstat higher than the recommended 150 mg once daily may cause prolongation of the QT interval, a heart rhythm condition. This risk is increased when the medication is combined with other drugs known to prolong the QT interval.

Hepatic Impairment

For individuals with moderate to severe liver impairment, a dosage adjustment is necessary. The liver is responsible for clearing the drug from the system, and impaired function can lead to higher levels of the medication in the body.

Drug Interactions

Berotralstat can affect how the body processes other medications. It may increase the levels of drugs that are substrates of certain enzymes (CYP2D6 and CYP3A4) or transporters (P-gp). This can lead to an increased risk of side effects from those other medications. Common interactions include:

• Certain antidepressants and antipsychotics
• Specific heart medications
• Cyclosporine

Pregnancy and Lactation

There is limited clinical data regarding the use of berotralstat in pregnant women or its presence in human breast milk. The potential risks and benefits should be discussed with a healthcare provider.

Pregnancy

There are no adequate and well-controlled studies of berotralstat in pregnant women. While animal studies did not show evidence of harm to the fetus at doses significantly higher than the recommended human dose, human data are currently insufficient to determine if there is a drug-associated risk of birth defects or miscarriage.

Breastfeeding

It is not known whether berotralstat is present in human breast milk, how it affects milk production, or if it has any effect on a breastfed infant. Animal studies have shown that the drug is present in the milk of lactating rats. Because of the potential for adverse reactions in a nursing infant, the benefits of breastfeeding should be weighed against the mother's clinical need for the medication.

If you are pregnant, planning to become pregnant, or breastfeeding, you should discuss the potential risks and benefits of berotralstat with your healthcare provider to determine the best course of treatment.

Available Forms

Berotralstat is available in the following form:

• Oral Capsule: This medication is taken by mouth, typically once daily with food.

The capsules are provided in blister packs for storage and administration.

FDA Approval Status

The U.S. Food and Drug Administration (FDA) approved berotralstat in December 2020. It was the first oral, non-steroidal treatment option approved specifically for the prevention of hereditary angioedema (HAE) attacks.

Approved Indications

Berotralstat is indicated for routine prophylaxis to prevent attacks of hereditary angioedema in adults and pediatric patients aged 12 years and older. It is designed for long-term, daily use to reduce the frequency of swelling episodes.

Limitations of Use

The FDA-approved labeling includes specific limitations regarding the use of this medication:

• It should not be used to treat an acute HAE attack. Patients must have access to separate rescue medications for the immediate treatment of breakthrough symptoms.
• The safety and effectiveness of berotralstat for the treatment of acute attacks have not been established.

Safety and Monitoring

There are currently no boxed warnings or Risk Evaluation and Mitigation Strategies (REMS) programs required by the FDA for berotralstat. As with all approved medications, it is subject to ongoing safety monitoring through the FDA MedWatch program to track adverse events and ensure continued safety for the public.

Insurance and Prior Authorization

Most insurance providers require a process called prior authorization before they will cover the cost of berotralstat. Your healthcare provider will need to submit specific medical information to your insurance company to justify the use of this medication for hereditary angioedema prophylaxis.

Specialty Pharmacy Requirements

Berotralstat is typically dispensed through specialty pharmacies. These pharmacies specialize in high-cost medications that require unique handling or monitoring. The cost may be influenced by the specific specialty pharmacy your insurance plan requires you to use.

Patient Support and Savings

Financial assistance may be available to help manage the out-of-pocket costs of berotralstat. Many patients utilize manufacturer-sponsored programs, such as copay savings cards for those with commercial insurance. For patients who are uninsured or meet certain income requirements, patient assistance programs may provide the drug at no cost or a significantly reduced rate.

Generic Status

There is currently no generic version of berotralstat available. Brand-name specialty drugs generally have higher costs than generic medications. The price will remain high until a generic alternative is approved by the FDA and becomes available on the market.