Berinert | Pharmacology Mentor

Generic Name

Berinert

Mechanism

Berinert selectively inhibits plasma kallikrein in the kallikrein–kinin system.
• Kallikrein blockade prevents cleavage of high‑mobility group box 1 (HMGB1) and the conversion of high‑molecular‑weight kininogen into bradykinin.
• Reduced bradykinin levels dampen vasodilation, capillary leakage, and edema characteristic of HAE.
• The antagonist is rapid‑acting, with onset of effect within minutes of intravenous administration.

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Pharmacokinetics

Parameter	Typical Value	Comments
Volume of distribution	~50 mL/kg	Reflects plasma‑bound drug; does not widely diffuse into tissues.
Half‑life	35–45 min	Clearance is rapid; repeated dosing is required for sustained inhibition.
Clearance	0.15–0.18 L/min/kg	Primarily hepatic; no renal excretion.
Route of elimination	Metabolism in the liver	No significant drug–drug interactions reported.

*Infusion* must be administered intravenously; oral or subcutaneous routes are not indicated.

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Indications

Acute treatment of spontaneous HAE attacks in adults and adolescents >12 yrs.
Prophylaxis before procedures likely to induce HAE (surgery, dental work, trauma, childbirth, hormonal changes).
Pre‑hospital care for severe, life‑threatening swelling, including airway compromise.

Berinert is approved in the EU and selected EU‑EFTA markets; it is not yet FDA‑approved for US use.

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Contraindications

Known hypersensitivity to human plasma proteins or to any component of the formulation.
Severe heart failure (NYHA class III/IV) and uncontrolled hypertension – avoid persistent infusion.
Pregnancy: Limited data; generally reserved for severe, life‑threatening HAE attacks or when other therapies are unavailable.
Allergy to transfusion products: monitor for anaphylaxis or serum sickness.

Dosing

> Important: All doses below refer to the European formulation and assume an adult weight of 70 kg.

Situation	Typical Dose	Frequency	Notes
Acute attack	30 U/kg (max 30 U)	IV over 15–30 min	Repeat 15 min if no response.
Pre‑operative prophylaxis (2 h before)	30 U/kg (30 U max)	IV over 15–30 min	Re‑dose 2 h after first infusion.
Ongoing prophylaxis (multiple exposures)	30 U/kg	IV 30 min each time	Can be given 24–48 h apart, as dictated by risk.
Sub‑clinical prophylaxis	30 U/Kg up to 720 U	IV daily	For patients with frequent attacks.

• Infusion must be performed by experienced personnel; monitor for signs of hypersensitivity.
• Premedicate with antihistamines or corticosteroids in high‑risk patients.

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Adverse Effects

Common (≤10 %)
• Mild infusion reactions: flushing, urticaria, pruritus.
• Headache, mild fever.

Serious (>1 %)
• Hypersensitivity/anaphylaxis.
• Severe dyspnea or respiratory distress.
• Transient hypertension due to infusion, rare.

Adverse events are dose‑related and typically resolve quickly after discontinuation of the infusion.

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Monitoring

Vital signs (BP, HR, O2 sat) before, during, and after infusion.
Look for airway compromise in patients with facial or laryngeal edema.
Laboratory tests: CBC, electrolytes, renal & hepatic function on a regular basis (baseline and before each dose if on prophylaxis).
Clinical assessment: Check response within 15 min; assess reduction in edema volume and symptom relief.

Do not routinely measure kallikrein or bradykinin levels—they lack clinical correlation.

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Clinical Pearls

Rapid reversal of bradykinin: Berinert’s onset is within minutes; most severe attacks resolve fully in <2 h, a significant advantage over icatibant or fresh frozen plasma.
Intravenous route only: Ensure IV access is adequate; if line failure, consider rapid conversion to a plasma‑derived complement inhibitor.
Pre‑procedure timing: Administer 30 min prior to surgery and repeat 2 h after to cover the peak peritonsillitis.
Differential diagnosis: If swelling does not improve within 30 min, consider angioedema from mast cell degranulation—switch to antihistamines or corticosteroids.
Storage: Keep refrigerated (2–8 °C) and protected from light; thaw at room temperature before use.
Cross‑referrals: In the US, Berinert can be accessed via special‑indication programs; coordinate with a pharmacology pharmacist.

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• *Prepared by:* Your Pharmacology Assistant

*Last updated:* 2024‑06