Dosing & Uses
Dosage Forms & Strengths
IV solution
- 10 mg/mL
Heparin Neutralization
1-1.5 mg per 100 USP units of heparin; not to exceed 50 mg
Monitor APTT 5-15 min after dose then in 2-8 hr
In accidental overdoses of heparin, consider t1/2 heparin 60-90 min
In setting without bleeding complications, consider observation, rather than reversal of anticoagulation with protamine (avoids ADR's)
Complex of protamine and heparin may degrade over time requiring further doses
Dalteparin or Tinzaparin Overdose
1 mg protamine for 100 units dalteparin or tinzaparin; if PTT prolonged 4hr after protamine overdose administer 0.5 mg per 100 units of dalteparin or tinzaparin
Enoxaparin Overdose
1 mg per mg enoxaparin (if enoxaparin overdose given within 8 hr); if >8 hr of overdose or bleeding continues after 4 hr after first dose, give 0.5 mg protamine per mg enoxaparin
Time Elapsed Since Heparin Dose
Dose of protamine (mg) to neutralize 100 units of heparin
- <1/2 hr: 1-1.5 mg/100 units of heparin
- 30-120 min: 0.5-0.75 mg/100 units of heparin
- >2 hr: 0.25-0.375 mg/100 units of heparin
Dosage Forms & Strengths
IV solution
- 10 mg/mL
Heparin Neutralization (Off-label)
~1 mg protamine neutralizes 100 units of heparin; not to exceed 50 mg/dose
Monagle P, et al. Chest 2008:133(6 Suppl):S887-S968
Time elapsed since heparin dose
- Protamine dose to neutralize 100 units of heparin
- <1/2 hr: 1 mg
- 30-120 min: 0.5-0.75 mg
- >2 hr: 0.25-0.375 mg
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (1)
- mifepristone
mifepristone, protamine. Other (see comment). Contraindicated. Comment: Mifepristone may lead to excessive post abortion bleeding in pts. on anticoagulant therapy.
Serious - Use Alternative (51)
- abciximab
protamine, abciximab. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Enhanced risk of hemorrhage.
- allopurinol
allopurinol increases effects of protamine by decreasing metabolism. Avoid or Use Alternate Drug.
- amobarbital
amobarbital decreases effects of protamine by increasing metabolism. Avoid or Use Alternate Drug.
- anagrelide
protamine, anagrelide. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Enhanced risk of hemorrhage.
- antithrombin alfa
antithrombin alfa and protamine both increase anticoagulation. Avoid or Use Alternate Drug.
- antithrombin III
antithrombin III and protamine both increase anticoagulation. Avoid or Use Alternate Drug.
- argatroban
argatroban and protamine both increase anticoagulation. Avoid or Use Alternate Drug.
- azithromycin
azithromycin increases effects of protamine by decreasing metabolism. Avoid or Use Alternate Drug.
- bazedoxifene/conjugated estrogens
bazedoxifene/conjugated estrogens decreases effects of protamine by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- bemiparin
bemiparin and protamine both increase anticoagulation. Avoid or Use Alternate Drug.
- bivalirudin
bivalirudin and protamine both increase anticoagulation. Avoid or Use Alternate Drug.
- butabarbital
butabarbital decreases effects of protamine by increasing metabolism. Avoid or Use Alternate Drug.
- butalbital
butalbital decreases effects of protamine by increasing metabolism. Avoid or Use Alternate Drug.
- cefamandole
cefamandole increases effects of protamine by pharmacodynamic synergism. Avoid or Use Alternate Drug.
- cilostazol
protamine, cilostazol. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Enhanced risk of hemorrhage.
- clarithromycin
clarithromycin increases effects of protamine by decreasing metabolism. Avoid or Use Alternate Drug.
- clopidogrel
protamine, clopidogrel. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Enhanced risk of hemorrhage.
- conjugated estrogens
conjugated estrogens decreases effects of protamine by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- dalteparin
dalteparin and protamine both increase anticoagulation. Avoid or Use Alternate Drug.
- dipyridamole
protamine, dipyridamole. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Enhanced risk of hemorrhage.
- enoxaparin
enoxaparin and protamine both increase anticoagulation. Avoid or Use Alternate Drug.
- eptifibatide
protamine, eptifibatide. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Enhanced risk of hemorrhage.
- erythromycin base
erythromycin base increases effects of protamine by decreasing metabolism. Avoid or Use Alternate Drug.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate increases effects of protamine by decreasing metabolism. Avoid or Use Alternate Drug.
- erythromycin lactobionate
erythromycin lactobionate increases effects of protamine by decreasing metabolism. Avoid or Use Alternate Drug.
- erythromycin stearate
erythromycin stearate increases effects of protamine by decreasing metabolism. Avoid or Use Alternate Drug.
- estradiol
estradiol decreases effects of protamine by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- estrogens conjugated synthetic
estrogens conjugated synthetic decreases effects of protamine by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- estropipate
estropipate decreases effects of protamine by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- fondaparinux
fondaparinux and protamine both increase anticoagulation. Avoid or Use Alternate Drug.
- heparin
heparin and protamine both increase anticoagulation. Avoid or Use Alternate Drug.
- levonorgestrel intrauterine
levonorgestrel intrauterine, protamine. Either decreases effects of the other by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Risk of thromboembolic disorders.
- levonorgestrel oral
levonorgestrel oral, protamine. Either decreases effects of the other by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Risk of thromboembolic disorders.
- levothyroxine
levothyroxine increases effects of protamine by pharmacodynamic synergism. Avoid or Use Alternate Drug.
- liothyronine
liothyronine increases effects of protamine by pharmacodynamic synergism. Avoid or Use Alternate Drug.
- mestranol
mestranol decreases effects of protamine by pharmacodynamic antagonism. Contraindicated. Risk of thromboembolic disorders.
- pentobarbital
pentobarbital decreases effects of protamine by increasing metabolism. Avoid or Use Alternate Drug.
- phenindione
phenindione and protamine both increase anticoagulation. Avoid or Use Alternate Drug.
- phenobarbital
phenobarbital decreases effects of protamine by increasing metabolism. Avoid or Use Alternate Drug.
- prasugrel
protamine, prasugrel. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Enhanced risk of hemorrhage.
- primidone
primidone decreases effects of protamine by increasing metabolism. Avoid or Use Alternate Drug.
- quinine
quinine increases effects of protamine by unknown mechanism. Avoid or Use Alternate Drug.
- roxithromycin
roxithromycin increases effects of protamine by decreasing metabolism. Avoid or Use Alternate Drug.
- secobarbital
secobarbital decreases effects of protamine by increasing metabolism. Avoid or Use Alternate Drug.
- sulfadiazine
sulfadiazine increases effects of protamine by decreasing metabolism. Avoid or Use Alternate Drug.
sulfadiazine increases effects of protamine by plasma protein binding competition. Avoid or Use Alternate Drug. - sulfamethoxazole
sulfamethoxazole increases effects of protamine by decreasing metabolism. Avoid or Use Alternate Drug.
sulfamethoxazole increases effects of protamine by plasma protein binding competition. Avoid or Use Alternate Drug. - sulfisoxazole
sulfisoxazole increases effects of protamine by decreasing metabolism. Avoid or Use Alternate Drug.
sulfisoxazole increases effects of protamine by plasma protein binding competition. Avoid or Use Alternate Drug. - thyroid desiccated
thyroid desiccated increases effects of protamine by pharmacodynamic synergism. Avoid or Use Alternate Drug.
- tibolone
tibolone increases effects of protamine by pharmacodynamic synergism. Avoid or Use Alternate Drug.
- ticlopidine
protamine, ticlopidine. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Enhanced risk of hemorrhage.
- tirofiban
protamine, tirofiban. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Enhanced risk of hemorrhage.
Monitor Closely (89)
- aceclofenac
protamine and aceclofenac both increase anticoagulation. Modify Therapy/Monitor Closely.
- acemetacin
protamine and acemetacin both increase anticoagulation. Modify Therapy/Monitor Closely.
- agrimony
protamine and agrimony both increase anticoagulation. Modify Therapy/Monitor Closely.
- alfalfa
protamine and alfalfa both increase anticoagulation. Modify Therapy/Monitor Closely.
- American ginseng
protamine and American ginseng both increase anticoagulation. Modify Therapy/Monitor Closely.
- anamu
protamine and anamu both increase anticoagulation. Use Caution/Monitor.
- aspirin
protamine and aspirin both increase anticoagulation. Modify Therapy/Monitor Closely.
- aspirin rectal
protamine and aspirin rectal both increase anticoagulation. Modify Therapy/Monitor Closely.
- aspirin/citric acid/sodium bicarbonate
protamine and aspirin/citric acid/sodium bicarbonate both increase anticoagulation. Modify Therapy/Monitor Closely.
- azapropazone
azapropazone increases effects of protamine by plasma protein binding competition. Use Caution/Monitor.
- azathioprine
azathioprine decreases effects of protamine by unknown mechanism. Use Caution/Monitor.
- budesonide
budesonide, protamine. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.
- capecitabine
capecitabine increases effects of protamine by unspecified interaction mechanism. Use Caution/Monitor.
- carbamazepine
carbamazepine decreases levels of protamine by increasing metabolism. Use Caution/Monitor.
- celecoxib
protamine and celecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.
- chitosan
chitosan increases effects of protamine by Other (see comment). Use Caution/Monitor. Comment: Chitosan can decrease GI absorption of vitamin K, enhancing anticoagulant effects.
- choline magnesium trisalicylate
protamine and choline magnesium trisalicylate both increase anticoagulation. Modify Therapy/Monitor Closely.
- cinnamon
protamine and cinnamon both increase anticoagulation. Modify Therapy/Monitor Closely.
- conjugated estrogens, vaginal
conjugated estrogens, vaginal decreases effects of protamine by pharmacodynamic antagonism. Modify Therapy/Monitor Closely. Risk of thromboembolic disorders.
- cordyceps
protamine and cordyceps both increase anticoagulation. Modify Therapy/Monitor Closely.
- cornsilk
cornsilk decreases effects of protamine by pharmacodynamic antagonism. Use Caution/Monitor. Cornsilk contains vitamin K; consume a consistent amount daily.
- cortisone
cortisone, protamine. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.
- danshen
protamine and danshen both increase anticoagulation. Use Caution/Monitor.
- deflazacort
deflazacort, protamine. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.
- devil's claw
protamine and devil's claw both increase anticoagulation. Use Caution/Monitor.
- dexamethasone
dexamethasone, protamine. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.
- diclofenac
protamine and diclofenac both increase anticoagulation. Modify Therapy/Monitor Closely.
- diflunisal
protamine and diflunisal both increase anticoagulation. Modify Therapy/Monitor Closely.
diflunisal increases effects of protamine by plasma protein binding competition. Use Caution/Monitor. - dong quai
protamine and dong quai both increase anticoagulation. Modify Therapy/Monitor Closely.
- epoprostenol
protamine and epoprostenol both increase anticoagulation. Modify Therapy/Monitor Closely.
- ethanol
ethanol increases effects of protamine by unknown mechanism. Use Caution/Monitor. Acute EtOH intoxication.
- ethotoin
protamine increases levels of ethotoin by unknown mechanism. Use Caution/Monitor.
ethotoin, protamine. Other (see comment). Use Caution/Monitor. Comment: Hydantoin anticonvulsants increase anticoagulant effects at first, then decrease those effects with continued use (2+ wks). There are multiple mechanisms involved, including enzyme induction, plasma protein binding site competition, and additive effects on prothrombin time. - etodolac
protamine and etodolac both increase anticoagulation. Modify Therapy/Monitor Closely.
- fenbufen
protamine and fenbufen both increase anticoagulation. Modify Therapy/Monitor Closely.
- fennel
protamine and fennel both increase anticoagulation. Modify Therapy/Monitor Closely.
- fenoprofen
protamine and fenoprofen both increase anticoagulation. Modify Therapy/Monitor Closely.
- feverfew
protamine and feverfew both increase anticoagulation. Modify Therapy/Monitor Closely.
- fludrocortisone
fludrocortisone, protamine. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.
- flurbiprofen
protamine and flurbiprofen both increase anticoagulation. Modify Therapy/Monitor Closely.
- forskolin
protamine and forskolin both increase anticoagulation. Modify Therapy/Monitor Closely.
- fosphenytoin
protamine increases levels of fosphenytoin by unknown mechanism. Use Caution/Monitor.
fosphenytoin, protamine. Other (see comment). Use Caution/Monitor. Comment: Hydantoin anticonvulsants increase anticoagulant effects at first, then decrease those effects with continued use (2+ wks). There are multiple mechanisms involved, including enzyme induction, plasma protein binding site competition, and additive effects on prothrombin time. - garlic
protamine and garlic both increase anticoagulation. Modify Therapy/Monitor Closely.
- ginger
protamine and ginger both increase anticoagulation. Modify Therapy/Monitor Closely.
- ginkgo biloba
protamine and ginkgo biloba both increase anticoagulation. Modify Therapy/Monitor Closely.
- glucagon intranasal
glucagon intranasal increases effects of protamine by unknown mechanism. Use Caution/Monitor.
- horse chestnut seed
protamine and horse chestnut seed both increase anticoagulation. Modify Therapy/Monitor Closely.
- hydrocortisone
hydrocortisone, protamine. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.
- ibuprofen
protamine and ibuprofen both increase anticoagulation. Modify Therapy/Monitor Closely.
- ibuprofen IV
protamine and ibuprofen IV both increase anticoagulation. Modify Therapy/Monitor Closely.
- indomethacin
protamine and indomethacin both increase anticoagulation. Modify Therapy/Monitor Closely.
- iodine (radioactive)
iodine (radioactive) decreases effects of protamine by pharmacodynamic antagonism. Use Caution/Monitor.
- ketoprofen
protamine and ketoprofen both increase anticoagulation. Modify Therapy/Monitor Closely.
- ketorolac
protamine and ketorolac both increase anticoagulation. Modify Therapy/Monitor Closely.
- ketorolac intranasal
protamine and ketorolac intranasal both increase anticoagulation. Modify Therapy/Monitor Closely.
- lofepramine
lofepramine increases levels of protamine by decreasing metabolism. Use Caution/Monitor.
- lornoxicam
protamine and lornoxicam both increase anticoagulation. Modify Therapy/Monitor Closely.
- meclofenamate
protamine and meclofenamate both increase anticoagulation. Modify Therapy/Monitor Closely.
- mefenamic acid
protamine and mefenamic acid both increase anticoagulation. Modify Therapy/Monitor Closely.
- meloxicam
protamine and meloxicam both increase anticoagulation. Modify Therapy/Monitor Closely.
- methimazole
methimazole decreases effects of protamine by pharmacodynamic antagonism. Use Caution/Monitor.
- methylprednisolone
methylprednisolone, protamine. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.
- mistletoe
protamine increases and mistletoe decreases anticoagulation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- nabumetone
protamine and nabumetone both increase anticoagulation. Modify Therapy/Monitor Closely.
- naproxen
protamine and naproxen both increase anticoagulation. Modify Therapy/Monitor Closely.
- nettle
protamine increases and nettle decreases anticoagulation. Effect of interaction is not clear, use caution. Modify Therapy/Monitor Closely.
- oxaprozin
protamine and oxaprozin both increase anticoagulation. Modify Therapy/Monitor Closely.
- panax ginseng
protamine and panax ginseng both increase anticoagulation. Modify Therapy/Monitor Closely.
- parecoxib
protamine and parecoxib both increase anticoagulation. Modify Therapy/Monitor Closely.
- pau d'arco
protamine and pau d'arco both increase anticoagulation. Modify Therapy/Monitor Closely.
- pegaspargase
pegaspargase increases effects of protamine by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of bleeding events.
- phenytoin
protamine increases levels of phenytoin by unknown mechanism. Use Caution/Monitor.
phenytoin, protamine. Other (see comment). Use Caution/Monitor. Comment: Hydantoin anticonvulsants increase anticoagulant effects at first, then decrease those effects with continued use (2+ wks). There are multiple mechanisms involved, including enzyme induction, plasma protein binding site competition, and additive effects on prothrombin time. - phytoestrogens
protamine and phytoestrogens both increase anticoagulation. Modify Therapy/Monitor Closely.
- piroxicam
protamine and piroxicam both increase anticoagulation. Modify Therapy/Monitor Closely.
- prednisolone
prednisolone, protamine. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.
- prednisone
prednisone, protamine. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.
- propafenone
propafenone increases effects of protamine by decreasing metabolism. Use Caution/Monitor.
- propylthiouracil
propylthiouracil decreases effects of protamine by pharmacodynamic antagonism. Use Caution/Monitor.
- reishi
protamine and reishi both increase anticoagulation. Modify Therapy/Monitor Closely.
- rifabutin
rifabutin decreases levels of protamine by increasing metabolism. Use Caution/Monitor.
- salicylates (non-asa)
protamine and salicylates (non-asa) both increase anticoagulation. Modify Therapy/Monitor Closely.
- salsalate
protamine and salsalate both increase anticoagulation. Modify Therapy/Monitor Closely.
- Siberian ginseng
protamine and Siberian ginseng both increase anticoagulation. Modify Therapy/Monitor Closely.
- sulfasalazine
protamine and sulfasalazine both increase anticoagulation. Modify Therapy/Monitor Closely.
- sulindac
protamine and sulindac both increase anticoagulation. Modify Therapy/Monitor Closely.
- tipranavir
tipranavir increases effects of protamine by pharmacodynamic synergism. Use Caution/Monitor. Tipranavir has mild antiplatelet activity that may incr bleeding risk.
- tolfenamic acid
protamine and tolfenamic acid both increase anticoagulation. Modify Therapy/Monitor Closely.
- tolmetin
protamine and tolmetin both increase anticoagulation. Modify Therapy/Monitor Closely.
- triamcinolone acetonide injectable suspension
triamcinolone acetonide injectable suspension, protamine. Other (see comment). Use Caution/Monitor. Comment: Corticosteroids may decrease anticoagulant effects by increasing blood coagulability; conversely, they may impair vascular integrity, thus increasing bleeding risk. Monitor INR closely.
- triclofos
triclofos increases effects of protamine by unspecified interaction mechanism. Use Caution/Monitor.
Minor (18)
- acetaminophen
acetaminophen increases effects of protamine by unknown mechanism. Minor/Significance Unknown.
- acetaminophen IV
acetaminophen IV increases effects of protamine by unknown mechanism. Minor/Significance Unknown.
- acetaminophen rectal
acetaminophen rectal increases effects of protamine by unknown mechanism. Minor/Significance Unknown.
- alprostadil intracavernous/urethral
alprostadil intracavernous/urethral increases effects of protamine by pharmacodynamic synergism. Minor/Significance Unknown.
- chlorella
chlorella decreases effects of protamine by pharmacodynamic antagonism. Minor/Significance Unknown. Theoretical, due to vitamin K content.
- demeclocycline
demeclocycline increases effects of protamine by pharmacodynamic synergism. Minor/Significance Unknown.
- dexmethylphenidate
dexmethylphenidate increases effects of protamine by decreasing metabolism. Minor/Significance Unknown.
- doxycycline
doxycycline increases effects of protamine by pharmacodynamic synergism. Minor/Significance Unknown.
- glyburide
glyburide increases effects of protamine by unspecified interaction mechanism. Minor/Significance Unknown.
- heparin
protamine decreases effects of heparin by Other (see comment). Minor/Significance Unknown. Comment: This combination produces an insoluble salt.
- mineral oil
mineral oil decreases levels of protamine by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- minocycline
minocycline increases effects of protamine by pharmacodynamic synergism. Minor/Significance Unknown.
- oxytetracycline
oxytetracycline increases effects of protamine by pharmacodynamic synergism. Minor/Significance Unknown.
- quinidine
quinidine increases effects of protamine by decreasing metabolism. Minor/Significance Unknown.
- serdexmethylphenidate/dexmethylphenidate
serdexmethylphenidate/dexmethylphenidate increases effects of protamine by decreasing metabolism. Minor/Significance Unknown.
- tetracycline
tetracycline increases effects of protamine by pharmacodynamic synergism. Minor/Significance Unknown.
- verteporfin
protamine decreases effects of verteporfin by pharmacodynamic antagonism. Minor/Significance Unknown.
- vitamin E
vitamin E, protamine. Mechanism: pharmacodynamic antagonism. Minor/Significance Unknown. Vitamin E at RDA does not change INR in pts. on chronic warfarin therapy; megadoses (~10x RDA) may enhance anticoagulant effects in vitamin K deficient pts.
Adverse Effects
Frequency Not Defined
Anaphylaxis
Hypotension
N/V
Decreased O2 consumption
Flushing
Pulmonary hypertension
Uncontrollable bleeding
Circulatory collapse
Pulmonary edema
Warnings
Black Box Warnings
Protamine sulfate can cause severe hypotension, cardiovascular collapse, noncardiogenic pulmonary edema, catastrophic pulmonary vasoconstriction, and pulmonary hypertension
Risk factors include high dose or overdose, rapid administration, repeated doses, previous administration of protamine, and current or previous use of protamine-containing drugs (NPH insulin, protamine zinc insulin, and certain beta-blockers).
Allergy to fish, previous vasectomy, severe left ventricular dysfunction, and abnormal preoperative pulmonary hemodynamics also may be risk factors. In patients with any of these risk factors, the risk to benefit of administration of protamine sulfate should be carefully considered. Vasopressors and resuscitation equipment should be immediately available in case of a severe reaction to protamine.
Protamine should not be given when bleeding occurs without prior heparin use
Contraindications
Hypersensitivity
Previous intolerance to drug
Cautions
Heparin rebound causing bleeding may occur 8-9 hr after protamine administration
May be ineffective in cardiac surgery patients despite adequate dose
Rapid infusion reactions can cause severe hypotensive reactions
Because of anticoagulant effect of the drug, it is unwise to give more than 50 mg over a short period unless a larger dose is clearly needed
Patients with history of allergy to fish may develop hypersensitivity reactions to drug, although no relationship established to date between allergic reactions to protamine and fish allergy
Prior exposure
- Previous exposure to protamine can induce a humoral immune response and predispose susceptible individuals to development of untoward reactions from subsequent use of drug
- Patients exposed to protamine through use of protamine-containing insulin or during heparin neutralization may experience life-threatening reactions and fatal anaphylaxis upon receiving large doses of protamine intravenously
- Severe reactions to intravenous protamine can occur in absence of local or systemic allergic reactions to subcutaneous injection of protamine-containing insulin
- Reports of presence of antiprotamine antibodies in sera of infertile or vasectomized men suggest that some of these individuals may react to use of protamine sulfate
- Fatal anaphylaxis has been reported in one patient with no prior history of allergies
Bleeding risk
- Hyperheparinemia or bleeding reported 30 minutes to 18 hours after cardiac surgery (under cardiopulmonary bypass) in spite of complete neutralization of heparin by adequate doses of protamine sulfate at end of operation
- Important to keep patient under close observation after cardiac surgery; administer additional doses of protamine sulfate if indicated by coagulation studies, such as heparin titration test with protamine and determination of plasma thrombin time
Pregnancy & Lactation
Pregnancy Category: C
Lactation: not known if excreted in breast milk
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Protamine that is strongly basic combines with acidic heparin forming a stable complex and neutralizes the anticoagulant activity of both drugs
Pharmacokinetics
Half-life elimination: 7 min
Onset: 5 min
Duration: 2 hr
Vd: 5.4 L
Metabolism: Unknown
Clearance: 1.4 L/min
Administration
IV Incompatibilities
Additive: cephalosporins, penicillins
Syringe: diatrizoate meglumine 52%, diatrizoate sodium, ioxaglate meglumine 39.3%, ioxaglate sodium 19.6%
IV Preparation
Reconstitute with 5 mL sterile water
Resulting solution equals 10 mg/mL
IV Administration
Inject without further dilution over 1-3 min; maximum of 50 mg in any 10 min period
For IV use only
Administer slow IVP (50 mg over 10 min)
Rapid IV infusion causes hypotension
Storage
Refrigerate
Avoid freezing
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| protamine intravenous - | 10 mg/mL vial |  | |
| protamine intravenous - | 10 mg/mL vial |  |
Copyright © 2010 First DataBank, Inc.
Patient Handout
protamine intravenous
NO MONOGRAPH AVAILABLE AT THIS TIME
USES: Consult your pharmacist.
HOW TO USE: Consult your pharmacist.
SIDE EFFECTS: Consult your pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Consult your pharmacist.
DRUG INTERACTIONS: Consult your pharmacist.Keep a list of all your medications with you, and share the list with your doctor and pharmacist.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: No monograph available at this time.
MISSED DOSE: Consult your pharmacist.
STORAGE: Consult your pharmacist.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.
Information last revised July 2016. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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