Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution:
Fibryga: ~1 g [exact potency labeled on vial]
RiaSTAP: 900-1300 mg [contains albumin (human); exact potency labeled on vial]
Pharmacology
Mechanism of Action
Fibrinogen (coagulation factor I), a protein found in normal plasma, is required to clot blood. Fibrinogen concentrate made from pooled human plasma replaces this protein which is missing or reduced in patients with a congenital fibrinogen deficiency.
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: Fibryga: Patients 12 to 53 years: 70.2 ± 29.9 mL/kg (range: 36.9 to 149.1 mL/kg); RiaSTAP: Patients 8 to 61 years: 52.7 ± 7.48 mL/kg (range: 36.22 to 67.67 mL/kg)
Excretion
RiaSTAP: Clearance is faster in pediatric patients <16 years than adults
Patients <16 years: 0.73 ± 0.14 mg/L
Patients ≥16 years: 0.53 ± 0.07 mg/L
Half-Life Elimination
Similar to biological fibrinogen
Biological fibrinogen: 100 hours (Kamath 2003)
Fibryga: Patients 12 to 53 years: 75.9 ± 23.8 (40 to 157 hours)
RiaSTAP:
Patients <16 years: 69.9 ± 8.5 hours
Patients ≥16 years: 82.5 ± 20 hours
Use: Labeled Indications
Congenital fibrinogen deficiency: Treatment of acute bleeding episodes in patients with congenital fibrinogen deficiency, including afibrinogenemia and hypofibrinogenemia.
Contraindications
Severe, immediate hypersensitivity reactions, including anaphylaxis to fibrinogen, human plasma-derived products, or any component of the formulation.
Dosage and Administration
Dosing: Adult
Congenital fibrinogen deficiency: IV: Note: Maintain a target fibrinogen level of 100 mg/dL for minor bleeding and 150 mg/dL for major bleeding.
When baseline fibrinogen level is known:
Fibryga: Dose (mg/kg) = [Target level (mg/dL) - measured level (mg/dL)] divided by 1.8 (mg/dL per mg/kg body weight)
RiaSTAP: Dose (mg/kg) = [Target level (mg/dL) - measured level (mg/dL)] divided by 1.7 (mg/dL per mg/kg body weight)
When baseline fibrinogen level is not known: 70 mg/kg
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Note: Dosing must be individualized for each patient based on the extent of bleeding, laboratory values, clinical condition of the patient, and target fibrinogen concentration.
Congenital fibrinogen deficiency; treatment of acute bleeding: Note: The recommended target fibrinogen concentration is 100 mg/dL for minor bleeding and 150 mg/dL for major bleeding.
Initial dose:
When baseline fibrinogen concentration is known: IV:
RiaSTAP: Infants, Children, and Adolescents (Kreuz 2005; Manco-Johnson 2009; RiaSTAP prescribing information [UK] 2016):
Dose (mg/kg) = [Target fibrinogen concentration (mg/dL) - measured fibrinogen concentration (mg/dL)] divided by 1.7 (mg/dL per mg/kg body weight)
Fibryga: Adolescents:
Dose (mg/kg) = [Target fibrinogen concentration (mg/dL) - measured fibrinogen concentration (mg/dL)] divided by 1.8 (mg/dL per mg/kg body weight)
When baseline fibrinogen level is not known: Fibryga, RiaSTAP: Infants, Children, and Adolescents: IV: 70 mg/kg
Adjust dose based on laboratory values and condition of patient. Administer additional doses if the fibrinogen concentration falls below 80 mg/dL for minor bleeding and below 130 mg/dL for major bleeding until hemostasis is achieved.
Reconstitution
Fibryga: Prior to reconstitution, warm both powder and sterile water for injection to room temperature; if water bath is used for warming, the water bath should not exceed 37°C (98°F). Reconstitute with 50 mL of SWFI; gently swirl until dissolved (~5 to 10 minutes), do not shake.
RiaSTAP: Transfer 50 mL of SWFI into fibrinogen concentrate vial. Gently swirl until dissolved; do not shake. Solution should be colorless and clear to slightly opalescent; discard if cloudy or contains particulates.
Administration
IV: For IV administration only; infuse at a rate not exceeding 5 mL/minute. Solution should be infused at room temperature. Do not administer with other products or IV solutions. Administration should be completed within 8 hours (RiaSTAP) or 4 hours (Fibryga) after reconstitution.
Storage
Fibryga: Store intact vials at 2°C to 25°C (36°F to 77°F) in original carton; do not freeze. Protect from light. Discard partially used vials. Reconstituted solution should be used within 4 hours; do not refrigerate or freeze.
RiaSTAP: As of May 2019, the manufacturer recommends storing intact vials at 2°C to 8°C (36°F to 46°F) (prior recommendation was to store at 2°C to 25°C [36°F to 77°F]) in original carton; do not freeze. Protect from light. Discard partially used vials. Reconstituted solution is stable for 8 hours when stored at 20°C to 25°C (68°F to 77°F).
Drug Interactions
There are no known significant interactions.
Adverse Reactions
1% to 10%:
Central nervous system: Headache (>1%)
Dermatologic: Erythema (≤8%), pruritus (≤8%)
Gastrointestinal: Vomiting (>5%)
Neuromuscular & skeletal: Weakness (>5%)
Miscellaneous: Fever (>5%)
<1%, postmarketing, and/or case reports: Anaphylaxis, arterial thrombosis, chills, deep vein thrombosis, dyspnea, hypersensitivity reaction, myocardial infarction, nausea, pulmonary embolism, skin rash, thromboembolism
Warnings/Precautions
Concerns related to adverse effects:
- Hypersensitivity: Hypersensitivity reactions (eg, hives, generalized urticaria, chest tightness, wheezing, hypotension, anaphylaxis) may occur. In the event of hypersensitivity reactions, treatment should be discontinued immediately.
- Thrombotic events: Thrombosis may occur spontaneously in patients with congenital fibrinogen deficiency with or without fibrinogen replacement therapy. Thromboembolic events have been reported in patients receiving fibrinogen concentrate. Consider potential risk of thrombosis with use; monitor for signs and symptoms of thrombosis.
Dosage form specific issues:
- Human plasma: Product of human plasma; may potentially contain infectious agents which could transmit disease (eg, viruses and theoretically the Creutzfeldt-Jakob disease [CJD]). Screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces the risk. Infections thought to be transmitted by this product should be reported to the manufacturer.
Other warnings/precautions:
- Appropriate use: Not indicated for the treatment of dysfibrinogenemia.
Monitoring Parameters
Fibrinogen level; signs/symptoms of hypersensitivity and thrombosis
Pregnancy
Pregnancy Considerations
Pregnant patients with congenital fibrinogen deficiency may have an increased risk of bleeding, thrombosis, and pregnancy loss; therefore, close surveillance is recommended. Maternal fibrinogen concentrations increase during pregnancy but do not protect against potential complications. Prophylaxis throughout pregnancy may be needed and higher doses may be required as pregnancy progresses. Replacement therapy may be initiated prior to conception. Plasma derived fibrinogen concentrate may be used for treatment or prevention of bleeding in patients with severe deficiency (RCOG [Pavord 2017]).
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Have patient report immediately to prescriber signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), signs of blood clots (numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood) severe dizziness, passing out, loss of strength and energy, diarrhea, yellow skin, severe headache, fast breathing, nausea, vomiting, or chills (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
