Argatroban

What is Argatroban?

• Argatroban is a direct thrombin inhibitor, used as prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT).
• It is also used in adult patients with or at risk for HIT undergoing percutaneous coronary intervention (PCI).

Argatroban

Argatroban pocket binding

Argatroban 133

What are the uses of this medicine?

Argatroban is used:

• for prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (HIT).
• as an anticoagulant in adult patients with or at risk for HIT undergoing percutaneous coronary intervention (PCI).

How does this medicine work?

• Argatroban is a direct thrombin inhibitor that reversibly binds to the thrombin active site.
• Argatroban does not require the co-factor antithrombin III for antithrombotic activity.
• Argatroban exerts its anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; activation of protein C; and platelet aggregation.
• Argatroban is capable of inhibiting the action of both free and clot-associated thrombin.
• At therapeutic concentrations, argatroban has little or no effect on related serine proteases (trypsin, factor Xa, plasmin, and kallikrein).

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• Major bleeding.
• History of hypersensitivity to this product.

What drug interactions can this medicine cause?

• Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.

Especially tell your doctor if you take:

• Heparin
• Oral Anticoagulant Agents (warfarin)
• thrombolytic agents
• glycoprotein IIb/IIIa antagonists

Is this medicine FDA approved?

• In 2000, argatroban was licensed by the Food and Drug Administration for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT).
• In 2002, it was approved for use during percutaneous coronary interventions in patients who have HIT or are at risk for developing it.

How should this medicine be used?

Recommended dosage: For Heparin-Induced Thrombocytopenia:

• The dose for heparin-induced thrombocytopenia without hepatic impairment is 2 mcg/kg/min administered as a continuous infusion.

For Percutaneous Coronary Intervention:

• The dose for patients with or at risk for heparin-induced thrombocytopenia undergoing percutaneous coronary intervention is started at 25 mcg/kg/min and a bolus of 350 mcg/kg administered via a large bore intravenous line over 3 to 5 minutes.

Administration:

• Argatroban is given intravenously.
• Argatroban Injection 250 mg/2.5 mL (100 mg/mL) must be diluted 100-fold by mixing with 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or Lactated Ringer’s Injection to a final concentration of 1 mg/mL.
• Argatroban Injection 50 mg/50 mL (1 mg/mL) is ready for intravenous infusion. Dilution is not required

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Injection: 250 mg/2.5 mL (100 mg/mL) single-dose vial.
• Injection: 50 mg/50 mL (1 mg/mL) ready for intravenous infusion single-dose vial.

This medicine is available in fallowing brand namesː

• argatroban

What side effects can this medication cause?

The most common side effects of this medicine include: In heparin-induced thrombocytopenia (HIT) patients:

• dyspnea, hypotension, fever, diarrhea, sepsis, and cardiac arrest.

In percutaneous coronary intervention (PCI) patients:

• chest pain, hypotension, back pain, nausea, vomiting and headache.

Less coomon side effects may include:

• Risk of Hemorrhage
• Intracranial Bleeding
• Allergic Reactions

What special precautions should I follow?

• Hemorrhage can occur at any site in the body in patients receiving argatroban. Unexplained fall in hematocrit or blood pressure may indicate hemorrhage.
• The risk of hemorrhage with argatroban may be increased in severe hypertension; immediately following lumbar puncture, spinal anesthesia, major surgery (especially involving the brain, spinal cord, or eye), hematologic conditions associated with increased bleeding tendencies such as congenital or acquired bleeding disorders, and gastrointestinal lesions such as ulcerations.
• Concomitant use of argatroban with antiplatelet agents, thrombolytics, and other anticoagulants may increase the risk of bleeding.
• Adjust starting dose and titrate carefully in patients with HIT who have moderate or severe hepatic impairment. Avoid use in PCI in patients with clinically significant hepatic impairment.
• The concomitant use of argatroban and warfarin results in prolongation of the PT and INR beyond that produced by warfarin alone.
• There are no data on the presence of argatroban in human milk, or its effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for argatroban and any potential adverse effects on the breastfed infant from argatroban or from the underlying maternal condition.
• All patients receiving anticoagulants, including pregnant women, are at risk for bleeding. Pregnant women receiving argatroban should be carefully monitored for evidence of excessive bleeding or unexpected changes in coagulation parameters.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• bleeding

• The symptoms of acute toxicity were loss of righting reflex, tremors, clonic convulsions, paralysis of hind limbs, and coma.

Management of overdosage:

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.
• Reversal of anticoagulant effect may take longer in patients with hepatic impairment.
• No specific antidote to argatroban is available; if life-threatening bleeding occurs and excessive plasma levels of argatroban are suspected, discontinue argatroban immediately and measure aPTT and other coagulation parameters.
• When argatroban was administered as a continuous infusion (2 mcg/kg/min) prior to and during a 4-hour hemodialysis session, approximately 20% of argatroban was cleared through dialysis.

Can this medicine be used in pregnancy?

• Limited data from published literature and postmarketing reports do not suggest an association between argatroban and adverse fetal developmental outcomes.
• Use of anticoagulants, including argatroban, may increase the risk of bleeding in the fetus and neonate. Monitor neonates for bleeding.

Can this medicine be used in children?

• Safety and effectiveness have not been established in pediatric patients.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• ARGATROBAN

Inactive ingredients:

• PROPYLENE GLYCOL
• ALCOHOL

Who manufactures and distributes this medicine?

Manufactured by:

• Exela Pharma Sciences, LLC
• Lenoir, NC

Distributed by:

• Hikma Pharmaceuticals USA Inc.
• Berkeley Heights, NJ

What should I know about storage and disposal of this medication?

• Store the vials in original carton at 20° to 25° C (68° to 77° F).
• Do not freeze.
• Retain in the original carton to protect from light.
• If the solution is cloudy, or if an insoluble precipitate is noted, the vial should be discarded.

• Dailymed label info on Argatroban
• FDA Argatroban