Orladeyo (Berotralstat)

Orladeyo is a targeted therapy that acts on the kallikrein‑kinin pathway to reduce the frequency of hereditary angioedema attacks.

• Hereditary angioedema (HAE): Decreases the number of swelling episodes in patients with type 1 or type 2 HAE.
• Acquired angioedema: May reduce attack frequency in rare cases of acquired C1‑inhibitor deficiency.
• Long‑term prophylaxis: Provides a convenient oral option for ongoing prevention of HAE attacks.

• Beretralstat is a highly selective, orally active inhibitor of plasma kallikrein. By blocking kallikrein activity, it prevents the conversion of high‑molecular‑weight kininogen to bradykinin, a peptide that increases vascular permeability and triggers swelling in hereditary angioedema. This reduction in bradykinin formation lowers the likelihood of angioedema attacks.

Adverse reactions reported with berotralstat are generally mild to moderate and reflect its systemic exposure.

Common Side Effects

• Dyspepsia: upset stomach or indigestion.
• Diarrhea: loose, watery stools.
• Abdominal pain: cramping or discomfort in the abdomen.
• Nausea: feeling of queasiness.
• Headache: mild to moderate head pain.
• Fatigue: feeling unusually tired.

Serious or Rare Side Effects

• Hepatotoxicity: elevated liver enzymes indicating potential liver injury.
• Angioedema: paradoxical swelling episodes.
• Anaphylaxis: severe allergic reaction requiring immediate medical attention.
• Thrombocytopenia: reduced platelet count.
• Severe rash or skin reactions.
• Acute pancreatitis: inflammation of the pancreas.

When prescribing beretralstat, clinicians should consider several safety aspects.

• Liver function monitoring: assess baseline enzymes and repeat periodically.
• Pregnancy and lactation: avoid use unless the benefit outweighs potential risk.
• Renal impairment: adjust use in patients with severe kidney disease.
• Concomitant medications: review for drugs that affect liver metabolism.
• Patient education: advise on recognizing signs of serious reactions.
• Store at ambient temperature: keep below 25 °C, in original packaging, protected from moisture.

Beretralstat may interact with other medicines that influence hepatic metabolism or affect the kallikrein‑kinin system.

Major Interactions (Avoid)

• Strong CYP3A4 inhibitors: may increase beretralstat exposure and risk of toxicity.
• Hepatotoxic drugs: concurrent use can raise the risk of liver injury.

Moderate Interactions (Monitor Closely)

• Moderate CYP3A4 inhibitors: may modestly raise beretraltarget .
• Medications that lower platelet .
• Anticoagulants antico .
• Herbal supplements .
• Food .
• Any .