Argatroban

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Generic: 50 mg/50 mL (50 mL); 250 mg/2.5 mL (2.5 mL); 125 mg/125 mL in NaCl 0.9% (125 mL); 250 mg/250 mL in NaCl 0.9% (250 mL [DSC]); 50 mg/50 mL in NaCl 0.9% (50 mL)

Solution, Intravenous [preservative free]:

Generic: 50 mg/50 mL (50 mL); 250 mg/2.5 mL (2.5 mL)

Pharmacology

Mechanism of Action

A direct, highly-selective thrombin inhibitor. Reversibly binds to the active thrombin site of free and clot-associated thrombin. Inhibits fibrin formation; activation of coagulation factors V, VIII, and XIII; activation of protein C; and platelet aggregation.

Pharmacokinetics/Pharmacodynamics

Distribution

174 mL/kg

Metabolism

Hepatic via hydroxylation and aromatization (major route). Metabolism via CYP3A4/5 (minor route) to four metabolites. Unchanged argatroban is the major plasma component. Plasma concentration of metabolite M1 is 0% to 20% of the parent drug and is three- to fivefold weaker.

Excretion

Feces (~65%; 14% unchanged); urine (~22%; 16% unchanged); low quantities of metabolites M2-4 in urine

Clearance:

Pediatric patients (seriously ill): 0.16 L/kg/hour; 50% lower than healthy adults

Pediatric patients (seriously ill with elevated bilirubin due to hepatic impairment or cardiac complications; n=4): 0.03 L/kg/hour; 80% lower than pediatric patients with normal bilirubin

Adult: 0.31 L/kg/hour (5.1 mL/kg/minute); hepatic impairment: 1.9 mL/kg/minute

Onset of Action

Immediate

Time to Peak

Steady-state: 1 to 3 hours

Half-Life Elimination

39 to 51 minutes; Hepatic impairment: 181 minutes

Protein Binding

Albumin: 20%; alpha₁-acid glycoprotein: 34%

Use: Labeled Indications

Heparin-induced thrombocytopenia: Prophylaxis or treatment of thrombosis in adults with heparin-induced thrombocytopenia (HIT).

Percutaneous coronary intervention: As an anticoagulant for percutaneous coronary intervention (PCI) in adults who have or are at risk of developing HIT.

Use: Off Label

Extracorporeal circuit patency of continuous renal replacement therapy (CRRT) in critically-ill patients with HIT (maintenance)c

Data from a limited number of patients studied suggest that prefilter administration of argatroban may be beneficial for the maintenance of extracorporeal circuit patency of continuous renal replacement therapy (CRRT) in critically-ill patients with HIT Link 2009. Additional data may be necessary to further define the role of argatroban in this setting.

Contraindications

Hypersensitivity to argatroban or any component of the formulation; major bleeding.

Canadian labeling: Additional contraindications (not in US labeling): Hereditary fructose intolerance.

Dosage and Administration

Dosing: Adult

Heparin-induced thrombocytopenia (HIT): Continuous IV infusion:

Initial dose: 2 mcg/kg/minute

Note: Critically-ill patients with normal hepatic function have become excessively anticoagulated with FDA-approved or lower starting doses of argatroban. Doses between 0.15 to 1.3 mcg/kg/minute were required to maintain aPTTs in the target range (Reichert 2003). In a prospective observational study of critically-ill patients with multiple organ dysfunction (MODS) and suspected or proven HIT, an initial infusion dose of 0.2 mcg/kg/minute was found to be sufficient and safe in this population (Beiderlinden 2007). Consider reducing starting dose to 0.2 mcg/kg/minute in critically-ill patients with MODS defined as a minimum number of two organ failures. Another report of a cardiac patient with anasarca secondary to acute renal failure had a reduction in argatroban clearance similar to patients with hepatic dysfunction. Reduced clearance may have been due to reduced liver perfusion (de Denus 2003). The American College of Chest Physicians has recommended an initial infusion rate of 0.5 to 1.2 mcg/kg/minute for patients with heart failure, MODS, severe anasarca, or postcardiac surgery (Linkins 2012).

Obesity: Pharmacokinetics and pharmacodynamics have not been evaluated prospectively in obese patients; however, retrospective data suggest using actual body weight to dose and that adjustment of initial dose is unnecessary in obesity (BMI up to 51 kg/m²) (Rice 2007).

Maintenance dose: Patient may not be at steady-state but measure aPTT after 2 hours; adjust dose until the steady-state aPTT is 1.5 to 3 times the initial baseline value, not exceeding 100 seconds; dosage should not exceed 10 mcg/kg/minute

Conversion to oral anticoagulant: Because there may be a combined effect on the INR when argatroban is combined with warfarin, loading doses of warfarin should not be used. Warfarin therapy should be started at the expected daily dose.

Patients receiving ≤2 mcg/kg/minute of argatroban: Argatroban therapy can be stopped when the INR is >4 on combined warfarin and argatroban therapy; repeat INR measurement in 4 to 6 hours; if INR is below therapeutic level, argatroban therapy may be restarted. Repeat procedure daily until desired INR on warfarin alone is obtained.

Patients receiving >2 mcg/kg/minute of argatroban: Reduce dose of argatroban to 2 mcg/kg/minute; measure INR for argatroban and warfarin 4 to 6 hours after dose reduction; argatroban therapy can be stopped when the INR on warfarin and argatroban combined therapy is >4. Repeat INR measurement in 4 to 6 hours; if INR is below therapeutic level, argatroban therapy may be restarted. Repeat procedure daily until desired INR on warfarin alone is obtained.

Note: The American College of Chest Physicians suggests monitoring chromogenic factor X assay when transitioning from argatroban to warfarin (Garcia 2012) or overlapping administration of warfarin for a minimum of 5 days until INR is within target range; recheck INR after anticoagulant effect of argatroban has dissipated (Guyatt 2012). Factor X levels <45% have been associated with INR values >2 after the effects of argatroban have been eliminated (Arpino 2005).

Prefilter administration for continuous renal replacement therapy (CRRT) in critically-ill patients with HIT (off-label use; Link 2009): 0.1 to 1.5 mcg/kg/minute. Note: Loading dose of 100 mcg/kg was administered during clinical trial; however, this may be unnecessary.

Percutaneous coronary intervention (PCI): IV:

Initial: Begin infusion of 25 mcg/kg/minute and administer bolus dose of 350 mcg/kg (over 3 to 5 minutes). ACT should be checked 5 to 10 minutes after bolus infusion; proceed with procedure if ACT >300 seconds.

Obesity: Pharmacokinetics and pharmacodynamics have not been evaluated prospectively in obese patients; however, retrospective data suggest using actual body weight to dose and that adjustment of initial dose is unnecessary in obesity (BMI up to 51 kg/m²) (Hursting 2008).

Following initial bolus:

ACT <300 seconds: Give an additional 150 mcg/kg bolus, and increase infusion rate to 30 mcg/kg/minute (recheck ACT in 5 to 10 minutes)

ACT >450 seconds: Decrease infusion rate to 15 mcg/kg/minute (recheck ACT in 5 to 10 minutes)

Once a therapeutic ACT (300 to 450 seconds) is achieved, infusion should be continued at this dose for the duration of the procedure.

If dissection, impending abrupt closure, thrombus formation during PCI, or inability to achieve ACT >300 seconds: An additional bolus of 150 mcg/kg, followed by an increase in infusion rate to 40 mcg/kg/minute may be administered (recheck ACT after each additional bolus or change in infusion rate).

Note: Post-PCI anticoagulation, if required, may be achieved by continuing infusion at a reduced dose of 2 mcg/kg/minute, with close monitoring of aPTT; adjust infusion rate as needed. Recheck ACT after each additional bolus or change in infusion rate.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Heparin-induced thrombocytopenia: Limited data available: Infants and Children ≤16 years: Note: Titration of maintenance dose must consider multiple factors including current argatroban dose, current aPTT, target aPTT, and clinical status of the patient. For specific uses, required maintenance dose is highly variable between patients. During the course of treatment, patient's dosing requirements may change as clinical status changes; critically ill patients and patients with hepatic dysfunction require lower dose; frequent dosage adjustments may be required in critical patients to maintain desired anticoagulant activity (Alsoufi 2004; Boshkov 2006; Keegan 2009). If argatroban therapy is used concurrently with or following FFP or a thrombolytic, some centers decrease dose by half (Alsoufi 2004).

Continuous IV infusion:

Initial dose: 0.75 mcg/kg/minute (Madabushi 2011)

Maintenance dose: Measure aPTT after 2 hours; adjust dose until the steady-state aPTT is 1.5 to 3 times the initial baseline value, not exceeding 100 seconds; adjust in increments of 0.1 to 0.25 mcg/kg/minute for normal hepatic function; reduce dose in hepatic impairment.

Note: A lower initial infusion rate may be needed in other pediatric patients with reduced clearance of argatroban (eg, patients with heart failure, multiple organ system failure, severe anasarca, postcardiac surgery or hepatic impairment). This precaution is based on adult studies of patients with these disease states who had reduced argatroban clearance.

Conversion to oral anticoagulant: Because there may be a combined effect on the INR when argatroban is combined with warfarin, loading doses of warfarin should not be used. Warfarin therapy should be started at the expected daily dose. Once combined INR on warfarin and argatroban is >4, stop argatroban. Repeat INR measurement in 4 to 6 hours; if INR is below therapeutic level, argatroban therapy may be restarted. Repeat procedure daily until desired INR on warfarin alone is obtained. Another option is to use factor X levels to monitor the effect of warfarin anticoagulation. When factor X level is <0.3, warfarin is considered therapeutic and at which time argatroban can be discontinued (Alsoufi 2004; Boshkov 2006).

Dosing: Obesity

Refer to adult dosing.

Reconstitution

Vials, 2.5 mL (100 mg/mL) concentrate: Prior to administration, each vial must be diluted with 250 mL of NS, D5W, or LR to a final concentration of 1 mg/mL. Diluent should be at room temperature. Mix by repeated inversion for 1 minute. A slight but brief haziness may occur upon mixing.

Premixed vials (50 mL or 125 mL) and single-use bags for infusion (1 mg/mL): No further dilution is required.

Administration

IV: The 2.5 mL (100 mg/mL) concentrated vial must be diluted to 1 mg/mL prior to administration. The premixed 50 mL or 125 mL vials and 250 mL bag (1 mg/mL) require no further dilution. The premixed 1 mg/mL vial may be inverted for use with an infusion set. For HIT, administer by continuous IV infusion. For PCI, administer by IV infusion and bolus (over 3 to 5 minutes through a large bore IV line).

Storage

Vials, 2.5 mL (100 mg/mL) concentrate: Prior to use, store vial in original carton at 20°C to 25°C (68°F to 77°F); excursions permitted to 15ºC to 30ºC (59ºF to 86°F). Do not freeze. Protect from light. The prepared solution, diluted in D5W, LR, or NS, is stable for 24 hours at 20°C to 25°C (68°F to 77°F) in ambient indoor light. Do not expose prepared solutions to direct sunlight. Prepared solutions that are protected from light and kept at 20°C to 25°C (68°F to 77°F) or under refrigeration at 2°C to 8°C (36°F to 46°F) are stable for up to 96 hours.

Premixed vials (50 mL or 125 mL) and single-use bags for infusion (1 mg/mL): Store at 20°C to 25°C (68°F to 77°F). Do not refrigerate or freeze. Protect from light.

Drug Interactions

Acalabrutinib: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Apixaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of apixaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Bromperidol: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy

Caplacizumab: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Collagenase (Systemic): Anticoagulants may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy

Dabigatran Etexilate: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of dabigatran etexilate with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Dasatinib: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Deferasirox: Anticoagulants may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy

Deoxycholic Acid: Anticoagulants may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy

Desirudin: Anticoagulants may enhance the anticoagulant effect of Desirudin. Consider therapy modification

Edoxaban: May enhance the anticoagulant effect of Anticoagulants. Refer to separate drug interaction content and to full drug monograph content regarding use of edoxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Management: Some limited combined use may be indicated during periods of transition from one anticoagulant to another. See the full edoxaban drug monograph for specific recommendations on switching anticoagulant treatment. Avoid combination

Estrogen Derivatives: May diminish the anticoagulant effect of Anticoagulants. More specifically, the potential prothrombotic effects of some estrogens and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of estrogens against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Exceptions: Tibolone. Consider therapy modification

Fat Emulsion (Fish Oil Based): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Hemin: May enhance the anticoagulant effect of Anticoagulants. Avoid combination

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Anticoagulants. Bleeding may occur. Management: Avoid such combinations when possible. If used concomitantly, increase diligence in monitoring for adverse effects (eg, bleeding, bruising, altered mental status due to CNS bleeds). Consider therapy modification

Ibritumomab Tiuxetan: Anticoagulants may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to an increased risk of bleeding. Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy

Inotersen: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Limaprost: May enhance the adverse/toxic effect of Anticoagulants. The risk for bleeding may be increased. Monitor therapy

MiFEPRIStone: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of bleeding may be increased. Avoid combination

Nintedanib: Anticoagulants may enhance the adverse/toxic effect of Nintedanib. Specifically, the risk for bleeding may be increased. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Obinutuzumab: Anticoagulants may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy

Omacetaxine: Anticoagulants may enhance the adverse/toxic effect of Omacetaxine. Specifically, the risk for bleeding-related events may be increased. Management: Avoid concurrent use of anticoagulants with omacetaxine in patients with a platelet count of less than 50,000/uL. Avoid combination

Omega-3 Fatty Acids: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Oritavancin: May diminish the therapeutic effect of Anticoagulants. Specifically, oritavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses. Monitor therapy

Pentosan Polysulfate Sodium: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Progestins: May diminish the therapeutic effect of Anticoagulants. More specifically, the potential prothrombotic effects of some progestins and progestin-estrogen combinations may counteract anticoagulant effects. Management: Carefully weigh the prospective benefits of progestins against the potential increased risk of procoagulant effects and thromboembolism. Use is considered contraindicated under some circumstances. Refer to related guidelines for specific recommendations. Consider therapy modification

Prostacyclin Analogues: May enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Monitor therapy

Rivaroxaban: Anticoagulants may enhance the anticoagulant effect of Rivaroxaban. Refer to separate drug interaction content and to full drug monograph content regarding use of rivaroxaban with vitamin K antagonists (eg, warfarin, acenocoumarol) during anticoagulant transition and bridging periods. Avoid combination

Salicylates: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Sugammadex: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Sulodexide: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Telavancin: May diminish the therapeutic effect of Anticoagulants. Specifically, telavancin may artificially increase the results of laboratory tests commonly used to monitor anticoagulant effectiveness, which could lead to incorrect decisions to decrease anticoagulant doses. Monitor therapy

Thrombolytic Agents: May enhance the anticoagulant effect of Anticoagulants. Management: See full drug monograph for guidelines for the use of alteplase for acute ischemic stroke during treatment with oral anticoagulants. Monitor therapy

Tibolone: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Tipranavir: May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Urokinase: May enhance the anticoagulant effect of Anticoagulants. Avoid combination

Vitamin E (Systemic): May enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Anticoagulants may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Vorapaxar: May enhance the adverse/toxic effect of Anticoagulants. More specifically, this combination is expected to increase the risk of bleeding. Avoid combination

Zanubrutinib: May enhance the adverse/toxic effect of Anticoagulants. Monitor therapy

Test Interactions

Argatroban may elevate PT/INR levels in the absence of warfarin. If warfarin is started, initial PT/INR goals while on argatroban may require modification. The American College of Chest Physicians suggests monitoring chromogenic factor X assay when transitioning from argatroban to warfarin (Garcia, 2012) or overlapping administration of warfarin for a minimum of 5 days until INR is within target range; recheck INR after anticoagulant effect of argatroban has dissipated (Guyatt, 2012). Factor Xa levels <45% have been associated with INR values >2 after the effects of argatroban have been eliminated (Arpino, 2005).

Adverse Reactions

As with all anticoagulants, bleeding is the major adverse effect of argatroban. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the intensity of anticoagulation and patient susceptibility.

>10%:

Cardiovascular: Chest pain (PCI related: <1% to 15%), hypotension (7% to 11%)

Genitourinary: Genitourinary tract hemorrhage (including hematuria; major: <1%; minor: 2% to 12%)

1% to 10%:

Cardiovascular: Vasodilation (1% to 10%), cardiac arrest (6%), bradycardia (5%), ventricular tachycardia (5%), myocardial infarction (PCI: 4%), angina pectoris (2%), coronary occlusion (2%), ischemic heart disease (2%), thrombosis (<1% to 2%)

Central nervous system: Headache (5%), pain (5%), intracranial hemorrhage (1% to 4%)

Dermatologic: Dermatological reaction (bullous eruption, rash; 1% to <10%)

Gastrointestinal: Nausea (5% to 7%), diarrhea (6%), vomiting (4% to 6%), abdominal pain (3% to 4%), gastrointestinal hemorrhage (major: <1% to 3%; minor: 3%)

Hematologic & oncologic: Decreased hematocrit (minor: ≤10%; major: <1%), decreased hemoglobin (minor: ≤10%; major: <1%; ≥2 g/dl), groin bleeding (5%), brachial bleeding (2%), minor hemorrhage (CABG related: 2%)

Neuromuscular & skeletal: Back pain (PCI related: 8%)

Respiratory: Dyspnea (10%), cough (3% to 10%), hemoptysis (minor: ≤1% to 3%)

Miscellaneous: Fever (<1% to 7%)

<1% (Limited to important or life-threatening): Aortic valve stenosis, bleeding at injection site (or access site; minor), cerebrovascular disease, gastroesophageal reflux disease, hypersensitivity reaction, local hemorrhage (limb and below-the-knee stump), pulmonary edema, retroperitoneal bleeding

Warnings/Precautions

Concerns related to adverse effects:

• Bleeding: The most common complication is bleeding and can occur at any site in the body. Use extreme caution in patients with hematologic conditions associated with increased bleeding (eg, congenital or acquired bleeding disorders, GI lesions); recent puncture of large vessels or organ biopsy; spinal anesthesia; immediately following lumbar puncture; recent cerebrovascular accident (CVA), stroke, intracerebral surgery, or other neuraxial procedure; severe hypertension; renal impairment; recent major surgery; recent major bleeding (intracranial, GI, intraocular, or pulmonary). Monitor for signs and symptoms of bleeding.
• Hypersensitivity: Airway, skin, and generalized hypersensitivity reactions have been reported.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage reduction is necessary; may require >4 hours to achieve full reversal of anticoagulant effects. Avoid use during PCI in patients with clinically significant hepatic impairment or elevations of ALT/AST ≥3 times ULN (has not been studied).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Critically ill patients: Use with caution in critically-ill patients; reduced clearance may require dosage reduction.

Monitoring Parameters

Monitor hemoglobin, hematocrit, signs and symptoms of bleeding.

HIT: Obtain baseline aPTT prior to start of therapy. Patient may not be at steady-state but check aPTT 2 hours after start of therapy to adjust dose, keeping the steady-state aPTT 1.5 to 3 times the initial baseline value (not exceeding 100 seconds).

PCI: Monitor ACT before dosing, 5 to 10 minutes after bolus dosing, and after any change in infusion rate and at the end of the procedure. Additional ACT assessments should be made every 20 to 30 minutes during extended PCI procedures.

Pregnancy

Pregnancy Considerations

Information related to argatroban in pregnancy is limited. Use of parenteral direct thrombin inhibitors in pregnancy should be limited to those women who have severe allergic reactions to heparin, including heparin-induced thrombocytopenia, and who cannot receive danaparoid (Guyatt 2012).

Patient Education

What is this drug used for?

• It is used to thin the blood so that clots will not form.
• It is used to treat blood clots.

Frequently reported side effects of this drug

• Diarrhea
• Nausea
• Vomiting
• Back pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding.
• Severe cerebrovascular disease like change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes.
• Severe dizziness
• Passing out
• Chest pain
• Abnormal heartbeat
• Severe headache
• Groin or pelvic pain
• Edema
• Shortness of breath
• Flushing
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.