Protamine Sulfate

Brand names Generic

Medication error Look-alike, sound-alike drug names potential ISMP reports that protamine sulfate has been confused with Protonix.(1) USP reports that protamine sulfate has been confused with ProAmatine, protirelin, and Protonix.(2)

Contraindications U.S. boxed warning: Protamine sulfate can cause severe hypotension, cardiovascular and warnings collapse, noncardiogenic pulmonary edema, catastrophic pulmonary vasoconstriction, and pulmonary hypertension. Appropriate facilities and supportive measures including resuscitative equipment and medications should be readily available in case of a severe reaction.(3) Risk factors include high dose, overdose, rapid administration, repeated doses, previous administration of protamine, and current or previous use of protamine-containing drugs. Allergy to fish, previous vasectomy, severe left ventricular dysfunction, and abnormal preoperative pulmonary hemodynamics may be risk factors. The risk to benefit should be considered in these patients.(3) Protamine sulfate should not be given when bleeding unrelated to heparin occurs.(3)

Infusion-related See U.S. Boxed Warning in the Contraindications and Warnings section. cautions In two case reports, doses of 3 and 4.5 mg/kg after cardiopulmonary bypass resulted in an anaphylactoid response in a 6- and a 2.5-year-old child, respectively.(4,5) Whether or not either child had any risk factors for this reaction was not clear.

Dosage Heparin: 1 mg of protamine sulfate will neutralize about 100 USP heparin units.(3,6) Because heparin’s half-life is short, over time less protamine is required. Only one-half the dose of protamine should be used if IV heparin has been discontinued for 30 minutes Individual doses should not exceed 50 mg.(3,6) (See the Comments section.) The following doses have been recommended for pediatric patients following IV injection of heparin(6):

Time Since Last Protamine Dose Ratio Heparin Dose Received (mg of protamine/100 units of heparin received in the previous 2 hr)

<30 min 1 mg

30–60 min 0.5–0.75 mg

60–120 min 0.375–0.5 mg

>120 min 0.25–0.375 mg

If the heparin was administered by deep sub-Q injection, 1–1.5 mg protamine/100 USP heparin units should be used. As an example, part of the dose (i.e., 25–50 mg) can be given over 10 minutes followed by an infusion of the remaining calculated dose over 8–16 hours.(7)

 748 Protamine Sulfate

Low molecular weight heparin (LMWH)(13,14)

Time (hr) Since Last LMWH Protamine Dose Ratio (mg of Dose Received protamine/100 anti-factor Xa units of LMWH given*,**)

<8 hr, first protamine dose 1 mg: 100 anti-factor Xa units LMWH

<8 hr, second protamine dose 0.5 mg: 100 anti-factor Xa units (if aPTT remains elevated 2–4 hr after first LMWH protamine dose)

8–12 hr 0.5 mg: 100 anti-factor Xa units LMWH

>12 hr May not be necessary

*100 units dalteparin = 100 anti-factor Xa units(14); 1 mg enoxaparin = 100 anti-factor Xa units.(13) **Protamine will neutralize only about 60% to 75% of dalteparin’s or 60% of enoxaparin’s anti-factor Xa activity.(13,14)

Dosage adjustment None noted in organ dysfunction

Maximum dosage 50 mg(3,6)

Additives Contains 9 mg NaCl/10 mg protamine.(3)

Suitable diluents D5W, NS(3,8)

Maximum 10 mg/mL(3) concentration

Preparation and Compatibility: A manufacturer states that protamine sulfate is incompatible with certain delivery antibiotics, including several of the cephalosporins and penicillins.(3)

IV push Contraindicated. Rapid administration may result in hypotension, bradycardia, pulmonary hypertension, etc.(3,6)

Intermittent infusion Infuse dose (maximum 50 mg) over 10 minutes(3,6) and ≤5 mg/min.(3,6)

Continuous infusion Not indicated

Other routes of Not indicated administration

 749