Details About Overdose or Poisoning Generic Salt :: Protamine
Drug Pharmacology ::
I. Pharmacology. Protamineis a cationic protein obtained from fish sperm that rapidly binds toand inactivates heparin. The onset of action after intravenousadministration is nearly immediate (30–60 seconds) and lasts up to 2hours. It also partially neutralizes low-molecular-weight heparins(LMWHs) and can act as an anticoagulant by inhibiting thromboplastin.
Drug Indications ::
Protamineis used for the reversal of the anticoagulant effect of heparin when anexcessively large dose has been administered inadvertently. Protaminegenerally is not needed for treatment of bleeding during standardheparin therapy because discontinuance of the heparin infusion isgenerally sufficient.
Protaminemay be used for reversal of regional anticoagulation in thehemodialysis circuit in cases in which anticoagulation of the patientwould be contraindicated (ie, active GI or CNS bleeding).
Drug Contra-Indications ::
Donot give protamine to patients with known sensitivity to the drug.Diabetic patients who have used protamine insulin may be at thegreatest risk for hypersensitivity reactions.
Protamine reconstituted with benzyl alcohol should not be used in neonates because of suspected toxicity from the alcohol.
Drug Adverse Effects ::
IV. Adverse effects
Rapidintravenous administration is associated with hypotension, bradycardia,and anaphylactoid reactions. Have epinephrine (see Epinephrine),diphenhydramine (Diphenhydramine), and cimetidine or another H2 blocker (Cimetidine and Other H2 Blockers) ready. Reaction may be prevented by avoiding high infusion rates of > 5 mg/min.
A rebound effect caused by heparin may occur within 8 hours of protamine administration.
Excess doses may lead to anticoagulation and the risk of bleeding.
Use in pregnancy. FDAcategory C (indeterminate). Maternal hypersensitivity reaction orhypotension could result in placental ischemia. However, this does notpreclude its acute, short-term use for a seriously symptomatic patient(see Table III–1).
Drug Lab Interactions ::
Drug or laboratory interactions. No known drug interactions other than the reversal of the effect of heparin.
Drug Dose Management ::
Dosage and method of administration
Administer protamine by slow intravenous injection over at least 1–3 minutes, not to exceed 50 mg in a 10-minute period.
The dose of protamine depends on the total dose and the time since administration of heparin.
1. If immediately after heparin administration, give 1–1.5 mg of protamine for each 100 units of heparin.
2. If 30–60 minutes after heparin administration, give only 0.5–0.75 mg of protamine for each 100 units of heparin.
3. If 2 hours or more after heparin administration, give only 0.25–0.375 mg of protamine for each 100 units of heparin.
4. If heparin was being administered by constant infusion, give 25–50 mg of protamine.
Ifthe patient is overdosed with an unknown quantity of heparin, give anempiric dose of 25–50 mg over 15 minutes (to minimize hypotension) anddetermine the activated partial thromboplastin time (aPTT) after 5–15minutes and for up to 2–8 hours to determine the need for additionaldoses.
For an overdose of a low-molecular-weight heparin:
1. Dalteparin or tinazaparin. Give 1 mg of protamine for every 100 anti-factor Xa international units of dalteparin and tinzaparin.
2. Enoxaparin. Give 1 mg of protamine for each 1 mg of enoxaparin.
3. Ifthe overdose amount is unknown, consider an empiric dose of 25–50 mggiven over 15 minutes. The anti-Xa:IIa factor ratios vary for LMWHproducts, and if they are high, as with a LMW heparinoid (eg,danaparoid), protamine may be ineffective. Anti-factor Xa activitylevels and aPTT values are usually not completely reversed, but thehemorrhagic effect may be neutralized. LMWHs have longer half-lives(4–6 hours) and accumulate with renal insufficiency; therefore,coagulopathies may persist and protamine should be considered evenseveral hours after the overdose.
Drug Chemical Formulations ::
Parenteral. Protamine sulfate, 50 mg in 5-mL vials or 250 mg in 25-mL vials.
The suggested minimum stocking level to treat a 70-kg adult for the first 24 hours is one 25 mL vial.