Version May 2024
Note: Patient variables (including age, clinical condition, severity of protein C deficiency, and plasma levels of protein C) will influence dosing and duration of therapy. Individualize frequency, duration, and dose based on protein C activity and patient pharmacokinetic profile.
Severe congenital protein C deficiency: IV:
Note: Maintain target peak protein C activity of 100% during acute episodes and short-term prophylaxis. After resolution of the acute episode or for long-term prophylaxis, maintain trough levels of protein C activity >25%. Higher peak levels of protein C may be necessary in prophylactic therapy of patients at increased risk for thrombosis (eg, infection, trauma, surgical intervention). If a patient is switched to a vitamin K antagonist, continue protein C replacement until stable anticoagulation is obtained. Initiate the vitamin K antagonist at a low dose and adjust incrementally, rather than using a loading dose.
Acute episode/short-term prophylaxis:
Initial dose: IV: 100 to 120 units/kg (for determination of recovery and half-life).
Subsequent 3 doses: IV: 60 to 80 units/kg every 6 hours (adjust to maintain peak protein C activity of 100%).
Maintenance dose: IV: 45 to 60 units/kg every 6 or 12 hours (adjust to maintain recommended maintenance trough protein C activity levels >25%).
Long-term prophylaxis: Maintenance dose: IV: 45 to 60 units/kg every 12 hours (recommended maintenance trough protein C activity levels >25%).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); monitor closely for sodium overload.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
(For additional information see "Protein C, concentrate from human plasma: Pediatric drug information")
Note: Patient variables (including age, clinical condition, and plasma levels of protein C) will influence dosing and duration of therapy. Individualize dosing based on protein C activity and patient's pharmacokinetic profile.
Severe congenital protein C deficiency: Infants, Children, and Adolescents:
Acute episode/short-term prophylaxis:
Initial dose: IV: 100 to 120 units/kg/dose (for determination of recovery and half-life) followed by subsequent 3 doses: 60 to 80 units/kg/dose every 6 hours adjusted to maintain peak protein C activity of 100%.
Maintenance dose: IV: 45 to 60 units/kg/dose every 6 or 12 hours adjusted to maintain recommended maintenance trough protein C activity levels >25%. Continue until desired anticoagulation achieved.
Long-term prophylaxis: Maintenance dose: IV: 45 to 60 units/kg/dose every 12 hours (recommended maintenance trough protein C activity levels >25%).
Note: Maintain target peak protein C activity of 100% during acute episodes and short-term prophylaxis. Maintain trough levels of protein C activity >25%. Higher peak levels of protein C may be necessary in prophylactic therapy of patients at increased risk for thrombosis (eg, infection, trauma, surgical intervention).
Purpura fulminans secondary to meningococcemia: Limited data available; optimal dose not established; role in management is not defined (Fuhrman 2017):
Infants, Children, and Adolescents: IV: 100 to 150 units/kg/dose every 6 hours for 72 hours, followed by 50 to 150 units/kg/dose every 12 hours (de Kleijn 2003; Fourier 2003). Other protocols have reported a daily dose of 100 units/kg/day with doses divided every 4 to 6 hours or as a continuous infusion (Veldman 2010) and others used a loading dose (100 units/kg/dose) followed by a continuous infusion (initial rate: 10 units/kg/hour) with titration of rate based upon protein C levels (target: 80 to 120 units/mL) (White 2000). Duration of therapy variable (1 to 24 days) (Veldman 2010); activated protein C levels and clinical response should be closely monitored.
Dosing based on placebo-controlled trials and retrospective reviews. In a phase II, double-blind, placebo-controlled, dose-finding study of 40 pediatric patients (median age: 2.3 years [range: 2.4 months to 16.1 years]), a dose of 100 to 150 units/kg/dose every 6 hours for 72 hours followed by 50 to 150 units/kg/dose every 12 hours until target symptom/sign resolution or treatment duration reaches 7 days was used; results showed dose-related increases in plasma activated protein C and resolution of coagulation imbalances (de Kleijn 2003). A retrospective review of 94 pediatric patients (newborn to 18 years) reported a median dose of 100 units/kg/day divided every 4 to 6 hours (daily dose range: 28 to 375 units/kg/day) in the majority of patients (78 of the 94 patients); the remaining patients received an initial bolus with the remainder of daily dose administered as a continuous IV infusion (dosing specifics were not provided); median treatment duration of 33 hours (range: 1 to 645 hours) (Veldman 2010). An open-label, prospective study of 36 patients (3 months to 72 years) reported an initial dose of 100 units/kg followed by a continuous IV infusion with an initial rate of 10 units/kg/hour adjusted daily to maintain plasma protein C concentration 80 to 120 units/mL (White 2000).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); monitor closely for sodium overload.
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
The following adverse drug reactions are derived from product labeling unless otherwise specified. Reported adverse reactions are for pediatric patients and adults.
Frequency not defined:
Hematologic & oncologic: Major hemorrhage
Hypersensitivity: Hypersensitivity reaction
Nervous system: Dizziness
Postmarketing:
Dermatologic: Diaphoresis
Local: Injection-site reaction
Nervous system: Restlessness
There are no contraindications listed in the manufacturer’s labeling.
Concerns related to adverse effects:
• Heparin-induced thrombocytopenia (HIT): Trace amounts of heparin contained within the formulation may lead to HIT; evaluate platelet counts if HIT is suspected.
• Hypersensitivity reactions: May contain trace amounts of mouse protein and/or heparin. Discontinue use in the presence of hypersensitivity/allergic reactions.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; monitor patients closely for sodium overload.
Special populations:
• Sodium-restricted patients: Use with caution in patients where sodium restriction is necessary.
Dosage form specific issues:
• Human plasma: Product of human plasma; may potentially contain infectious agents which could transmit disease; screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces this risk. Infections thought to be transmitted by this product should be reported to the manufacturer.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Ceprotin: 500 units (1 ea); 1000 units (1 ea) [contains albumin human, heparin, mouse (murine) and/or hamster protein]
No
Solution (reconstituted) (Ceprotin Intravenous)
500 unit (Price provided is per AHF Unit): $1.80
1000 unit (Price provided is per AHF Unit): $1.80
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
IV: Administer by intravenous injection at a rate not to exceed 2 mL/minute. In infants and children <10 kg, administration should not exceed a rate of 0.2 mL/kg/minute. Administration must be completed within 3 hours of solution preparation.
Parenteral: Administer by IV injection; infusion must be completed within 3 hours of solution preparation.
Neonates, Infants, and Children <10 kg: Rate should not exceed 0.2 mL/kg/minute
Children ≥10 kg and Adolescents: Rate should not exceed 2 mL/minute
Severe congenital protein C deficiency: Prevention and treatment of venous thrombosis and purpura fulminans in adults and pediatric patients with severe congenital protein C deficiency.
Ceprotin may be confused with aprotinin, Cipro
Protein C concentrate (human) may be confused with activated protein C (human, recombinant) which refers to drotrecogin alfa
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Anticoagulants: Protein C Concentrate (Human) may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Thrombolytic Agents: Protein C Concentrate (Human) may enhance the adverse/toxic effect of Thrombolytic Agents. Specifically, the risk of bleeding may be increased. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Protein C Concentrate (Human) may enhance the adverse/toxic effect of Vitamin K Antagonists. Specifically, the risk of warfarin-induced skin necrosis may be increased. Protein C Concentrate (Human) may diminish the therapeutic effect of Vitamin K Antagonists. This is effect is transient and occurs at the initiation of vitamin K antagonist therapy. Risk C: Monitor therapy
Protein C Concentrate is derived from purified human plasma.
Protein C Concentrate is derived from purified human plasma.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.
At maximum daily doses, product formulation contains sodium >200 mg.
Protein C activity (chromogenic assay) prior to and during therapy; signs and symptoms of bleeding; hemoglobin/hematocrit, PT/INR, platelet count; signs and symptoms of sodium overload in patients with renal impairment.
Maintain target peak protein C activity of 100% during acute episodes and short-term prophylaxis. After resolution of the acute episode or for long-term prophylaxis, maintain trough levels of protein C activity >25%. Higher peak levels of protein C may be necessary in prophylactic therapy of patients at increased risk for thrombosis (eg, infection, trauma, surgical intervention).
Converted to activated protein C (APC). APC is a serine protease which inactivates factors Va and VIIIa, limiting thrombotic formation. In vitro data also suggest inhibition of plasminogen activator inhibitor-1 (PAF-1) resulting in profibrinolytic activity, inhibition of macrophage production of tumor necrosis factor, blocking of leukocyte adhesion, and limitation of thrombin-induced inflammatory responses.
Note: Limited data suggests that infants and very young children may have a faster clearance, lower AUC and maximum serum concentration, larger volume of distribution, and shorter half-life than older subjects.
Onset of action: 30 minutes
Distribution: Vd: Median: 0.074L/kg (range: 0.044 to 0.165 L/kg)
Metabolism: Activated protein C (APC) inactivated by plasma protease inhibitors
Half-life elimination: Median: 9.8 hours; range: 4.9 to 14.7 hours
Time to peak, plasma: Tmax: 0.5 hours; range: 0.17 to 1.33 hours
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
