Yes

Antidote

Treatment of heparin overdosage; neutralize heparin during surgery or dialysis procedures

C

Hypersensitivity to protamine or any component

May not be totally effective in some patients following cardiac surgery despite adequate doses; may cause hypersensitivity reaction in patients with a history of allergy to fish (have epinephrine 1:1000 available) and in patients sensitized to protamine (via protamine zinc insulin); too rapid administration can cause severe hypotensive and anaphylactoid-like reactions. Heparin rebound associated with anticoagulation and bleeding has been reported to occur occasionally; symptoms typically occur 8-9 hours after protamine administration, but may occur as long as 18 hours later.

>10%:

Cardiovascular: Sudden fall in blood pressure, bradycardia

Respiratory: Dyspnea

1% to 10%: Hematologic: Hemorrhage

<1%: Hypotension, flushing, lassitude, nausea, vomiting, pulmonary hypertension, hypersensitivity reactions

Symptoms of overdose include hypertension; may cause hemorrhage; doses exceeding 100 mg may cause paradox anticoagulation

Refrigerate, avoid freezing; remains stable for at least 2 weeks at room temperature; incompatible with cephalosporins and penicillins; preservative-free formulation does not require refrigeration

Combines with strongly acidic heparin to form a stable complex (salt) neutralizing the anticoagulant activity of both drugs

Onset of effect: I.V. injection: Heparin neutralization occurs within 5 minutes

Protamine dosage is determined by the dosage of heparin; 1 mg of protamine neutralizes 90 USP units of heparin (lung) and 115 USP units of heparin (intestinal); maximum dose: 50 mg

Time elapsed: Immediate:

1-1.5 mg protamine to neutralize 100 units of heparin

Time elapsed: 30-60 minutes:

0.5-0.75 mg protamine to neutralize 100 units of heparin

Time elapsed: >2 hours:

0.25-0.375 mg protamine to neutralize 100 units of heparin

If heparin administered by deep S.C. injection, use 1-1.5 mg protamine per 100 units heparin; this may be done by a portion of the dose (eg, 25-50 mg) given slowly I.V. followed by the remaining portion as a continuous infusion over 8-16 hours (the expected absorption time of the S.C. heparin dose)

Coagulation test, APTT or ACT, cardiac monitor and blood pressure monitor required during administration

May cause drowsiness

None reported

No information available to require special precautions

No effects or complications reported

Report any difficulty breathing, rash or flushing, feeling of warmth, tingling or numbness, dizziness, or disorientation. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Consult prescriber if breast-feeding.

Parenteral: Reconstitute vial with 5 mL sterile water; if using protamine in neonates, reconstitute with preservative-free sterile water for injection; resulting solution equals 10 mg/mL; inject without further dilution over 1-3 minutes; maximum of 50 mg in any 10-minute period

Injection: 10 mg/mL (5 mL, 10 mL, 25 mL)

Aren C, "Heparin and Protamine Therapy," Semin Thorac Cardiovasc Surg, 1990, 2(4):364-72.

Horrow JC, "Protamine: A Review of Its Toxicity," Anesth Analg, 1985, 64(3):348-61.

Kondo NI, Maddi R, Ewenstein BM, et al, "Anticoagulation and Hemostasis in Cardiac Surgical Patients," J Card Surg, 1994, 9(4):443-61.

Lindblad B, "Protamine Sulfate: A Review of Its Effects - Hypersensitivity and Toxicity," Eur J Vasc Surg, 1989, 3(3):195-201.

Michelson AD, Bovill E, Monagle P, et al, "Antithrombic Therapy in Children," Chest, 1998, 114(5 Suppl):748S-69S.

Wakefield TW and Stanley JC, "Intraoperative Heparin Anticoagulation and Its Reversal," Semin Vasc Surg, 1996, 9(4):296-302.