Orladeyo, also known by its generic name berotralstat, is a prescription medication used to prevent attacks of hereditary angioedema (HAE) in adults and children 12 years and older. Unlike treatments for acute attacks, it is taken once daily to reduce the frequency of HAE episodes. While effective, understanding its potential side effects is crucial for proper and safe management. The side effects can range from common and manageable gastrointestinal issues to rare but serious cardiac risks associated with improper use.
Common Side Effects
Clinical studies have shown that most side effects associated with Orladeyo are gastrointestinal and tend to be mild to moderate in severity. These reactions are often most noticeable when starting treatment and may lessen or resolve with continued use.
Gastrointestinal Reactions
- Abdominal Pain: This is the most common side effect reported by people taking Orladeyo. It can be accompanied by discomfort or tenderness in the stomach area.
- Diarrhea: Many patients experience diarrhea, which is often mild and temporary.
- Vomiting and Nausea: Both vomiting and feelings of nausea are common, especially early in treatment.
- Heartburn (GERD): Some individuals report symptoms of gastroesophageal reflux disease, or GERD.
- Flatulence: Increased gas is a less common but reported side effect.
Other Common Effects
- Headache: Some people experience headaches.
- Back Pain: Back pain has also been identified as a common adverse reaction.
- Fatigue: Unusual tiredness or weakness can occur.
- Skin Rash: A rash was reported in a small percentage of clinical trial participants and typically resolved, even with continued treatment.
Serious Side Effects
While less frequent, Orladeyo can cause serious side effects, particularly if not taken as prescribed. It is vital for patients to be aware of these potential risks and to contact their healthcare provider if they experience any related symptoms.
QT Prolongation (Heart Rhythm Problem)
The most serious risk associated with Orladeyo is a heart rhythm abnormality known as QT prolongation. This is primarily a risk when patients take more than the recommended daily amount.
Symptoms to watch for include:
- Abnormal or irregular heartbeat
- Dizziness or feeling lightheaded
- Fainting
- Chest pain
- Shortness of breath
Elevated Liver Enzymes
Rarely, patients have experienced elevated liver enzymes, which could be a sign of liver damage. A healthcare provider may perform regular blood tests to monitor liver function.
Allergic Reaction
Though allergic reactions were not reported during clinical trials, they are possible with any medication. Seek immediate medical help if you experience signs of a severe allergic reaction, such as swelling of the face, tongue, or throat, or difficulty breathing.
Managing Side Effects
Several strategies can help manage the common side effects of Orladeyo:
- Take with Food: Always take your dose with food to help reduce the incidence and severity of gastrointestinal issues.
- Report Persistent GI Issues: If stomach problems persist for several weeks, talk to your doctor. Adjustments to how the medication is taken may be considered to help manage these effects.
- Consult Before Other Medications: For heartburn, consult your pharmacist before taking any over-the-counter acid reducers, as some medications can interact with Orladeyo.
- Do Not Take More Than Prescribed: Never take more of Orladeyo per day than prescribed by your doctor, as this significantly increases the risk of serious heart rhythm problems.
Comparison: Orladeyo vs. Takhzyro Side Effects
Orladeyo and Takhzyro (lanadelumab) are both used for HAE prevention, but differ in their administration and some side effect profiles.
| Feature | Orladeyo (berotralstat) | Takhzyro (lanadelumab) |
|---|---|---|
| Administration | Oral capsule, taken once daily. | Subcutaneous injection. |
| Common Side Effects | Abdominal pain, vomiting, diarrhea, heartburn, back pain, headache, fatigue. | Injection site reactions (pain, bruising, skin discoloration), headache, rash, diarrhea. |
| Serious Side Effects | QT prolongation with improper use, elevated liver enzymes. | Hypersensitivity reactions. |
| GI Symptoms | Common, typically occurring early in treatment. | Less frequent than injection site reactions. |
Drug Interactions
Before starting Orladeyo, inform your healthcare provider about all medications, vitamins, and herbal supplements you are taking. Orladeyo can interact with other drugs and affect their efficacy.
- P-gp Inducers: Avoid taking Orladeyo with P-gp inducers like rifampin or St. John's wort, as they can decrease the concentration and effectiveness of Orladeyo.
- CYP2D6, CYP3A4, or P-gp Substrates: Orladeyo can inhibit these enzymes, potentially increasing the concentration of other drugs. Close monitoring and dose adjustment are recommended for coadministered medications with a narrow therapeutic index, such as digoxin or cyclosporine.
Conclusion
While gastrointestinal distress is a common and often temporary side effect of Orladeyo, the most critical safety consideration is the risk of serious cardiac issues from improper use. Adhering strictly to the prescribed regimen is essential. For persistent GI side effects, adjusting how the medication is taken under medical supervision can be an effective solution. Regular communication with a healthcare provider is key to managing potential adverse effects and ensuring the medication remains a safe and effective part of an HAE management plan. You can review the complete prescribing information for Orladeyo to understand all warnings and precautions.
Important Considerations
- Patients with moderate or severe liver impairment or those chronically taking P-gp or BCRP inhibitors may require specific adjustments to how they take the medication.
- Orladeyo is not recommended for patients with end-stage renal disease.
- The medication is not intended to treat acute HAE attacks.
- The safety of Orladeyo during pregnancy and breastfeeding is not established.
