berotralstat

Therapeutic Classification: antiangioedema agents

Pharmacologic Classification: kallikrein inhibitors

Indications ⬆ ⬇

REMS

Prevention of hereditary angioedema (HAE) attacks.

Action ⬆ ⬇

Acts as a selective, reversible inhibitor of kallikrein, thereby inhibiting its action in initiating bradykinin production, part of the cascade of events in HAE.

Therapeutic effects:

Reduction in number of HAE attacks.

Pharmacokinetics ⬆ ⬇

Absorption: Unknown.

Distribution: Unknown.

Protein Binding: 99%.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP2D6 and CYP3A4 isoenzymes. Primarily excreted in feces (79%), with 9% excreted in urine (3.4% as unchanged drug).

Half-Life: 93 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	5 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

End-stage renal disease.

Use Cautiously in:

Moderate or severe hepatic impairment (↓ dose);
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Children <12 yr (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

CV: QT interval prolongation (with higher than recommended dosages)

GI: abdominal pain, diarrhea, gastroesophageal reflux disease, vomiting, flatulence

MS: back pain

Neuro: fatigue, headache

Interactions ⬆ ⬇

Drug-drug:

P-gp inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.
May ↑ levels and risk of toxicity of CYP2D6 substrates, including pimozide and thioridazine; closely monitor.
May ↑ levels and risk of toxicity of CYP3A4 substrates, including cyclosporine and fentanyl; closely monitor.
May ↑ levels and risk of toxicity of P-gp substrates, including digoxin; closely monitor serum digoxin concentrations.
May ↑ levels and risk of toxicity of desogestrel.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

Route/Dosage ⬆ ⬇

PO (Adults ): 150 mg once daily.

Hepatic Impairment

PO (Adults ): Moderate or severe hepatic impairment: 110 mg once daily.

Availability ⬆ ⬇

Capsules: 110 mg; 150 mg

Assessment ⬆ ⬇

Assess face, lips, extremities (bilateral arms, legs, hands, or feet) and abdomen for erythema marginatum (pale pink rash), which might indicate an HAE attack. Seek immediate medical care if needed. Do not take additional doses of berotralstat.
Monitor for persistent GI reactions (abdominal pain, vomiting, diarrhea). Consider ↓dose.

Lab Test Considerations:

Monitor baseline hepatic function and periodically during therapy.Monitor ECG for QT prolongation if dose >150 mg is taken.

Implementation ⬆ ⬇

PO: Take once daily with food.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Advise to take as directed. Do not take more than one capsule per day.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken, especially rifampin or St. John's wort, and to consult health care professional before taking other medications.
Advise patient to take usual rescue medication to treat an acute attack of HAE. Advise them not to take additional doses/higher doses due to risk for an abnormal heartbeat.
Rep: Notify health care professional if pregnancy is planned or suspected. Treatment with this therapy is not recommended during pregnancy. Monitor for HAE closely during pregnancy and for 72 hr after delivery. Breastfeeding may ↑ risk of HAE attacks. If prevention of attacks is needed during breastfeeding, other agents are recommended.

Evaluation/Desired Outcomes ⬆ ⬇

Reduction in number of HAE attacks.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

11014- Catalent Pharma Solutions, LLC
- 11014-0437-
  - 11014-0437-2- 1 BAG in 1 DRUM (11014-0437-2) / 22556 CAPSULE in 1 BAG

11014- Catalent Pharma Solutions, LLC
- 11014-0437-
  - 11014-0437-3- 1 BAG in 1 DRUM (11014-0437-3) / 20300 CAPSULE in 1 BAG

11014- Catalent Pharma Solutions, LLC
- 11014-0495-
  - 11014-0495-1- 1 BAG in 1 DRUM (11014-0495-1) / 27685 CAPSULE in 1 BAG

59116- Cambrex Charles City, Inc.
- 59116-5570-
  59116-5570-2- 18 kg in 1 DRUM (59116-5570-2)

72769- BioCryst Pharmaceuticals Inc.
- 72769-101- Orladeyo
  72769-101-01- 4 DOSE PACK in 1 CARTON (72769-101-01) / 1 BLISTER PACK in 1 DOSE PACK / 7 CAPSULE in 1 BLISTER PACK

72769- BioCryst Pharmaceuticals Inc.
- 72769-102- Orladeyo
  - 72769-102-01- 4 DOSE PACK in 1 CARTON (72769-102-01) / 1 BLISTER PACK in 1 DOSE PACK / 7 CAPSULE in 1 BLISTER PACK

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Pronunciation ⬇

Classifications ⬆ ⬇