Recombinant/plasma-derived protein C concentrate Pregnancy: Safety for use in human pregnancy has not been established in controlled clinical trials, although the product has been used safely in pregnant protein C-deficient women. No information is available on excretion of protein C in milk. The benefit of use during pregnancy or lactation must be judged against the risk for mother and baby, and it should be used only if clearly needed. Note the parvovirus B19 risk discussed in §4.4 (infection may be serious for pregnant women).

Protein C (Specialist drug)

Brand names: Ceprotin

Protein C concentrate is a human plasma-derived replacement therapy used in severe congenital protein C deficiency, including for purpura fulminans and warfarin-induced skin necrosis.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: Treatment of acute episodes and short-term prophylaxis (including invasive procedures): an initial dose of 60 to 80 IU/kg is advised (for determination of recovery and half-life). Long-term prophylaxis: 45 to 60 IU/kg every 12 hours.

Route: Intravenous injection after reconstitution of the powder with Sterilised Water for Injections; maximum injection rate 2 ml per minute

Frequency: Dose and interval are determined by laboratory measurement of protein C activity, not by a fixed schedule. In an acute thrombotic event measure protein C activity every 6 hours until the patient is stabilised, thereafter twice a day and always immediately before the next injection. If the response is satisfactory (chromogenic assay), dosing may be gradually reduced to 12-hourly, ensuring trough protein C activity >25% (>0.25 IU/ml). Long-term prophylaxis: every 12 hours.

eMC (CEPROTIN 1000 IU powder and solvent for solution for injection). Treatment should be initiated under the supervision of a physician experienced in substitution therapy with coagulation factors/inhibitors, where monitoring of protein C activity is feasible. The dose must be adjusted on the basis of laboratory assessment for each individual case. TARGETS: a protein C activity of 100% (1 IU/ml) should be achieved initially and activity maintained above 25% for the duration of treatment; for long-term prophylaxis ensure trough levels of 25% or more and adjust dose or frequency accordingly. The half-life of protein C may be severely shortened in certain clinical conditions such as acute thrombosis with purpura fulminans and skin necrosis. Patients treated during the acute phase of their disease may display much lower increases in protein C activity; wide individual variation means coagulation parameters should be checked regularly. In patients on prophylaxis, higher trough levels may be warranted where thrombotic risk is increased (infection, trauma, surgery). SUBCUTANEOUS ROUTE: in rare and exceptional cases, subcutaneous infusion of 250-350 IU/kg was able to produce therapeutic protein C plasma levels in patients with no intravenous access. COMBINATION WITH ORAL ANTICOAGULANTS: if switching to permanent prophylaxis with oral anticoagulants, protein C replacement is discontinued only when stable anticoagulation is obtained; during initiation of oral anticoagulant therapy start with a low dose and adjust incrementally rather than using a standard loading dose; maintain stable protein C activity above 0.25 IU/ml (chromogenic) before starting anticoagulation, monitor INR carefully, and maintain a protein C trough of about 10% or more during combination therapy. PAEDIATRIC: the SPC states that, based on limited clinical experience in children (reports and studies covering 83 patients), dosing guidelines for adult subjects are considered valid for the neonatal and paediatric population; no separate numeric paediatric regimen is given, so paedDose has been left null. For children with a body weight <10 kg the injection rate should not exceed 0.2 ml/kg/min. Clinician to verify any paediatric use against a children's formulary. Administration should be made within reach of life-supporting facilities in case acute, life-threatening allergic symptoms arise. Limited clinical data in patients with combined severe congenital protein C deficiency and APC resistance.

Dose adjustments

Renal

Safety and efficacy in patients with renal and/or hepatic impairment have not been established; no dose adjustment is specified. Patients with either condition should be monitored more closely.

Dose auto-extracted from UK Summary of Product Characteristics (SPC) via the eMC — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Hypersensitivity to the active substance or to any of the excipients
Hypersensitivity to mouse protein or to heparin — except for control of life-threatening thrombotic complications

Side effects

Allergic-type hypersensitivity reactions are possible with any intravenous protein product — early signs may include angioedema, burning and stinging at the injection site, chills, flushing, rash, pruritus, generalised urticaria, headache, hives, hypotension, lethargy, nausea, restlessness, tachycardia, tightness of the chest, tingling, vomiting and wheezing
Rash (rare)
Pruritus (rare)
Dizziness (rare)
Post-marketing, frequency not known: restlessness, hyperhidrosis, injection site reaction

Interactions

Oral anticoagulants, especially vitamin K antagonists (from SPC §4.2, which cross-refers to §4.5) — protein C replacement should be discontinued only when stable anticoagulation is obtained; start the oral anticoagulant at a low dose and adjust incrementally rather than using a standard loading dose; maintain protein C activity above 0.25 IU/ml before starting anticoagulation and a protein C trough of about 10% or more during combination therapy; monitor INR carefully
Heparin (from SPC §4.4) — the product may contain trace amounts of heparin, which may provoke heparin-induced allergic reactions with a rapid fall in platelet count (HIT); if HIT is suspected, check the platelet count immediately and stop therapy if necessary; patients with HIT should avoid heparin-containing drugs in future
NOTE: SPC section 4.5 was not captured in the fetched bundle — clinician to review the full §4.5 interactions section

Clinical monograph

How it works

It replaces deficient protein C, which after activation inactivates clotting factors Va and VIIIa, restoring a key natural anticoagulant pathway and reducing the prothrombotic state.

Prescribing in practice

Severe protein C deficiency carries a high thrombotic risk, and replacement should be co-ordinated with anticoagulation, particularly when initiating vitamin K antagonists, to avoid skin necrosis.
As a plasma-derived product it carries a theoretical infection-transmission risk and may cause hypersensitivity reactions.
It is administered intravenously by specialists with dosing guided by protein C activity levels per the SPC; paediatric use should follow a children's formulary.

Monitoring

Monitor protein C activity levels to guide dosing alongside clinical response and coagulation status.

Counselling the patient

Explain that this replaces a missing natural blood-thinning protein to prevent dangerous clotting.
Advise reporting any signs of allergic reaction during or after the infusion.

Evidence & guidelines

Use of protein C concentrate in severe congenital protein C deficiency is supported by established UK haematology practice and the SPC.

Reference: NICE; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways