Action and Spectrum

Actions and Spectrum: 

Actions: 

The primary action of berotralstat is the inhibition of plasma kallikrein, an enzyme involved in the production of bradykinin. Bradykinin is a potent vasodilator and is responsible for the symptoms associated with HAE attacks. By inhibiting plasma kallikrein, berotralstat helps to reduce the production of bradykinin, thereby preventing or reducing the severity and frequency of HAE attacks.

Spectrum: 

The spectrum of berotralstat’s effects is mainly focused on preventing HAE attacks. It does not provide immediate relief during an acute attack. Instead, it is taken regularly to reduce the frequency and severity of attacks over time. By providing continuous inhibition of plasma kallikrein, berotralstat helps to stabilize bradykinin levels and minimize the risk of sudden and unpredictable swelling episodes. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Abdominal pain (10-23%) 

Diarrhea (10-15%) 

Vomiting (10-15%) 

1-10% 

Gastroesophageal reflux disease (5-10%) 

Fatigue (6%) 

Flatulence (6%) 

Back pain (2-10%) 

Headache (9%)  

Frequency not defined 

Elevated ALT 

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hypersensitivity 

Caution 

• Hepatic impairment  
• Drug interactions 
• Renal impairment 
• Pregnancy 
• Breastfeeding 

Pregnancy / Lactation

Pregnancy consideration:  

Insufficient data are available regarding the usage in pregnant women. 

Breastfeeding warnings:  

No data is available regarding the excretion of this drug in breast milk.  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

berotralstat is a selective inhibitor of plasma kallikrein, an enzyme involved in the production of bradykinin. By inhibiting plasma kallikrein, berotralstat helps to reduce the production of bradykinin, a potent vasodilator that mediates the symptoms of hereditary angioedema (HAE) attacks. 

Pharmacodynamics: 

• Selective Inhibition of Plasma Kallikrein: berotralstat is a selective inhibitor of plasma kallikrein, an enzyme involved in the production of bradykinin. By binding to plasma kallikrein, berotralstat prevents its enzymatic activity and reduces the conversion of high-molecular-weight kininogen (HMWK) to bradykinin. 
• Reduction in Bradykinin Levels: Bradykinin is a potent vasodilator and increases vascular permeability, leading to the characteristic symptoms of hereditary angioedema (HAE) attacks. By inhibiting plasma kallikrein, berotralstat helps to reduce bradykinin production and maintain bradykinin levels within a normal range, thereby preventing or reducing the severity and frequency of HAE attacks. 
• Prophylactic Effect: berotralstat is used as a prophylactic medication for HAE, meaning it is taken regularly to prevent attacks rather than providing immediate relief during an acute attack. By providing sustained inhibition of plasma kallikrein, berotralstat helps to stabilize bradykinin levels and minimize the risk of sudden and unpredictable swelling episodes. 

Pharmacokinetics: 

Absorption 

The drug is absorbed systemically. 

Distribution 

The protein-bound is 99% 

Ratio of blood-to-plasma is 0.92 

Metabolism 

The drug is metabolized by CYP3A4 and CYP2D6  

Elimination and Excretion 

The half-life is 93 hours 

The drug is excreted 9% in urine and 79% in feces

Adminstartion

Administration: 

berotralstat should be taken at approximately the same time each day, with or without food. Follow the specific instructions prescribed by the healthcare professional provides or the medication’s label. The berotralstat tablet should be swallowed whole with water. Do not chew crush, or break before consumption. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: berotralstat 

Pronounced: BER-oh-TRAL-stat  

Why do we use berotralstat? 

berotralstat prevents hereditary angioedema (HAE) attacks in adults and adolescents aged 12. It helps in the reduction of bradykinin levels, which eases vasodilation. 

HAE attacks can significantly impact the quality of life of individuals affected by the condition. By reducing the severity and frequency of attacks, berotralstat can help improve overall well-being, minimize HAE’s physical and emotional burden, and enhance daily functioning.