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Prasugrel

Class: Platelet-Aggregation Inhibitors
Brands: Effient

Bleeding

Potential risk of serious (including fatal) bleeding.¹ ² ⁶ ¹⁰ (See Bleeding under Cautions.)

Avoid use in patients with active pathological bleeding, history of stroke/ TIA, or in those likely to undergo CABG.¹

Generally not recommended in patients ≥75 years of age because of increased risk of fatal and intracranial bleeding, except in certain high-risk patients (e.g., those with diabetes, history of MI) who may experience a greater net clinical benefit.¹ ⁵ ¹⁸ ⁷⁰ (See Geriatric Use under Cautions.)

Consider additional risk factors for bleeding such as body weight <60 kg, concomitant use of drugs that increase risk of bleeding, or other underlying conditions that may increase risk of bleeding.¹

Discontinue prasugrel at least 7 days prior to any surgery.¹

Suspect bleeding in any patient receiving prasugrel who is hypotensive and has recently undergone an invasive (e.g., PCI, coronary angiography) or surgical (e.g., CABG) procedure.¹

If bleeding occurs, attempt to manage without discontinuing therapy; increased risk of subsequent cardiovascular events possible with premature discontinuance, particularly in first few weeks following an acute coronary event or in patients with intracoronary stents.¹ ⁴³ ⁴⁴ ⁴⁵ ⁴⁶ ⁴⁷ ⁴⁸ ⁴⁹ ⁵⁴ ⁷⁰ (See Discontinuance of Therapy under Cautions.)

REMS:

FDA approved a REMS for prasugrel to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of prasugrel and consists of the following: medication guide and communication plan. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Platelet-activation and aggregation inhibitor; thienopyridine derivative.¹ ² ³ ⁴ ⁵ ⁶ ⁸ ¹³ ¹⁴ ¹⁵ ²⁸ ³⁰

Uses for Prasugrel

Acute Coronary Syndromes: Patients Undergoing PCI

Used in conjunction with aspirin to reduce the risk of thrombotic cardiovascular events (e.g., stent thrombosis, MI) in patients with acute coronary syndromes (ACS) undergoing PCI.¹ ²

Used in patients with unstable angina or non-ST-segment-elevation MI (NSTEMI) undergoing PCI and in patients with ST-segment elevation MI (STEMI) managed with primary or delayed (after medical treatment) PCI.¹ ²

Current standard of care in patients with ACS includes dual antiplatelet therapy with a thienopyridine derivative (e.g., clopidogrel, prasugrel) and aspirin.³ ⁶ ⁹ ¹⁶ ¹⁷ ²³ ²⁷ ⁶⁴ ⁶⁷ ⁷⁰ Increased inhibition of platelet aggregation associated with prasugrel appears to produce greater reductions in ischemic outcomes (e.g., stent thrombosis, MI) compared with standard dosages of clopidogrel in patients with ACS undergoing PCI; however, such benefits have been accompanied by an increased risk of bleeding.¹ ³ ⁵ ⁶ ⁷ ⁸ ⁹ ¹¹ ¹³ ¹⁴ ¹⁵ ¹⁷ ¹⁸ ⁶²

Some evidence suggests that certain patient populations (e.g., those with diabetes, previous MI) may be more likely to benefit from prasugrel’s greater inhibition of platelet aggregation, while others (e.g., patients ≥75 years, those weighing <60 kg, those with previous TIA/stroke) may experience harm;² ⁵ ¹⁴ ¹⁶ ¹⁷ ¹⁹ additional studies needed to confirm these findings.² ⁵ ¹³ ¹⁹

Precise role of prasugrel versus clopidogrel in the management of ACS remains to be fully established.¹³ ¹⁴ ¹⁷ ²⁰ ⁷⁰ When considering use, balance anticipated greater benefits against increased risk of bleeding.¹ ² ⁸ ⁹ ¹³ ¹⁴ ¹⁷ ⁷⁰

Prasugrel Dosage and Administration

General

It is generally recommended that antiplatelet agents be administered promptly upon presentation or diagnosis in patients with ACS.¹ ² ⁶⁴ ⁶⁶ ⁶⁷

Pretreatment with prasugrel may be considered prior to determining coronary anatomy in patients who are not likely to undergo CABG surgery; weigh benefits of pretreatment against risk of surgical bleeding in patients who may require urgent CABG.¹

In patients with STEMI who will undergo primary PCI, ACC and AHA currently recommend administration of a loading dose of either clopidogrel or prasugrel as early as possible before PCI or at the time of the procedure.⁷⁰

Administration

Administer orally without regard to meals.¹

Dosage

Available as prasugrel hydrochloride; dosage expressed in terms of prasugrel.¹

Adults

Acute Coronary Syndromes

Patients Undergoing PCI

Oral

60-mg initial loading dose followed by maintenance dosage of 10 mg daily; give in conjunction with aspirin (75–325 mg daily).¹ ACC and AHA recommend that the loading dose of prasugrel be administered as soon as possible in patients with STEMI undergoing primary PCI.⁷⁰ In patients with STEMI undergoing nonprimary PCI who have not received thrombolytic therapy and in whom coronary anatomy has been determined and PCI is planned, ACC and AHA recommend administering a 60-mg loading dose of prasugrel promptly and no later than 1 hour after PCI, followed by a maintenance dosage of 10 mg once daily.⁷⁰ Majority of patients in TRITON-TIMI 38 study received loading dose after first coronary guidewire was placed or within 1 hour of PCI.¹ ² ³

Consider reduced maintenance dosage in patients weighing <60 kg.¹ ⁶ ¹⁸ (See Low Body Weight under Dosage and Administration: Special Populations.)

Optimum duration of maintenance therapy not known; premature discontinuance in patients with intracoronary stents associated with thrombotic events, sometimes fatal.¹ ⁴³ ⁴⁴ ⁴⁵ ⁴⁶ ⁴⁷ ⁴⁸ ⁴⁹ ⁵⁴ ⁷⁰ (See Discontinuance of Therapy under Cautions.) Long-term antiplatelet therapy with a thienopyridine derivative is recommended in patients with intracoronary stents to prevent ischemic events.⁶⁵ ⁶⁶ ⁷⁰ In patients who receive a bare-metal or drug-eluting stent during PCI, ACC and AHA recommend daily maintenance therapy with clopidogrel or prasugrel for at least 12 months; earlier discontinuance may be considered if risk of morbidity from bleeding is thought to outweigh the anticipated benefit of such therapy.⁷⁰ ACC and AHA suggest consideration of extending thienopyridine therapy beyond 15 months in patients with ACS and drug-eluting stents.⁷⁰

Special Populations

Hepatic Impairment

No dosage adjustments required in patients with mild to moderate hepatic impairment (Child-Pugh Class A and B).¹ Not studied in patients with severe hepatic disease.¹

Renal Impairment

No dosage adjustments required.¹

Low Body Weight

May reduce maintenance dosage to 5 mg daily in patients who weigh <60 kg, although safety and efficacy of such lower dosages not established.¹ ⁶ ¹⁸ (See Bleeding under Cautions.)

Cautions for Prasugrel

Contraindications

Active pathological bleeding (e.g., peptic ulcer, intracranial hemorrhage).¹

History of stroke or TIA.¹

Warnings/Precautions

Warnings

Bleeding

Risk of serious, sometimes fatal bleeding.¹ ² ⁶ ¹⁰ Major and minor bleeding events, including life-threatening and fatal bleeding reported more frequently in patients receiving prasugrel than those who received clopidogrel in pivotal clinical study.¹ ² ⁶ ¹⁰

Greater risk of bleeding observed in patients ≥75 years of age, those weighing < 60 kg, and those with prior stroke or TIA.¹ ² Additional risk factors include recent trauma, recent surgery (e.g., CABG), recent or recurrent GI bleeding, active peptic ulcer disease, severe hepatic impairment, and concurrent use of drugs that increase risk of bleeding (e.g., oral anticoagulants, NSAIAs, thrombolytic agents).¹

Do not use in patients who are actively bleeding and/or who have a history of stroke or TIA.¹ ¹⁷ ¹⁸ Not recommended in patients likely to undergo emergent CABG.¹ (See CABG under Cautions.)

Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, PCI, CABG, or any other surgical procedure, even if there are no overt manifestations of bleeding.¹

If possible, manage bleeding without discontinuing prasugrel; premature discontinuance is associated with an increased risk of subsequent cardiovascular events.¹ (See Discontinuance of Therapy under Cautions.) May treat bleeding with platelet transfusions; however, transfusions within 6 hours of a loading dose or 4 hours of a maintenance dose may be less effective.¹ Withholding a dose not likely to resolve or prevent bleeding.¹

Cerebrovascular Events

Higher incidence of stroke (thrombotic and hemorrhagic) and no evidence of clinical benefit reported among patients with a history of stroke or TIA receiving prasugrel compared with clopidogrel in TRITON-TIMI 38 study.¹ ² Use not recommended in patients with a history of stroke or TIA; in general, discontinue prasugrel in those who experience such cerebrovascular events during therapy.¹ ¹⁸

CABG

Increased risk of bleeding in patients who undergo CABG surgery.¹ ² (See Bleeding under Cautions.) CABG-related major and minor bleeding events occurred substantially more frequently in patients who received prasugrel versus clopidogrel in pivotal clinical study.¹ ²

Discontinue prasugrel at least 7 days prior to CABG.¹ Do not initiate in patients who are likely to undergo urgent CABG.¹ May treat CABG-related bleeding with blood product transfusions (e.g., packed red blood cells, platelets).¹

Discontinuance of Therapy

Discontinue prasugrel in patients who develop active bleeding, stroke, or TIA during therapy.¹ Discontinue drug at least 7 days prior to elective surgery.¹ ⁷⁰

Avoid premature discontinuance of thienopyridine treatment because of the subsequent increased risk of ischemic complications.¹ ⁶ ⁴⁵ Premature discontinuance of dual antiplatelet therapy with clopidogrel and aspirin in patients with intracoronary stents has been associated with an increased risk of stent thrombosis, MI, and/or death.⁴³ ⁴⁴ ⁴⁵ ⁴⁶ ⁴⁷ ⁴⁸ ⁴⁹ ⁵⁴ Advise patients to never discontinue such therapy without consulting their prescribing clinician.¹ ⁴⁵ (See Advice to Patients.) If prasugrel must be temporarily discontinued because of an adverse event, reinstitute therapy as soon as possible.¹

Thrombotic Thrombocytopenic Purpura (TTP)

Reported rarely with use of other thienopyridine derivatives, sometimes after brief exposure (<2 weeks); potentially fatal.¹ ³¹ Characterized by thrombocytopenia, microangiopathic hemolytic anemia (schistocytes on peripheral blood smear), neurologic findings, renal dysfunction, and fever.¹ ³¹ Requires urgent treatment (e.g., plasmapheresis).¹

Specific Populations

Pregnancy

Category B.¹

Lactation

Distributed into milk in rats; not known whether distributed into human milk.¹ Use during nursing only if potential benefits outweigh risks.¹

Pediatric Use

Safety and efficacy not established in pediatric patients.¹

Geriatric Use

Geriatric patients, particularly those ≥75 years of age, appear to be at greater risk of bleeding (including fatal bleeding) with prasugrel therapy compared with younger patients.¹ Fatal bleeding and symptomatic intracranial hemorrhage occurred more often in patients ≥75 years of age receiving prasugrel compared with that in clopidogrel-treated patients in a large clinical study.¹

In general, avoid use in patients ≥75 years of age, but may consider use in certain geriatric patients with high-risk conditions (e.g., diabetes, previous MI) in whom a greater net clinical benefit has been demonstrated.¹ ⁵ ¹⁸ ⁷⁰

Hepatic Impairment

In patients with mild to moderate hepatic impairment (Child-Pugh Class A and B), inhibition of platelet aggregation was similar to that of healthy individuals.¹ Not specifically studied in patients with severe hepatic impairment; such patients generally are at higher risk of bleeding.¹

Renal Impairment

Inhibition of platelet aggregation similar in patients with moderate renal impairment (Cl_cr of 30–50 mL/minute) and healthy individuals.¹

Low Body Weight

Patients with low body weight (< 60 kg) have increased exposure to the active metabolite of prasugrel and appear to be at increased risk of bleeding.¹ (See Bleeding under Cautions.)

Common Adverse Effects

Bleeding, including life-threatening and fatal bleeding events.¹ ²

Interactions for Prasugrel

Metabolized principally by CYP3A4 and CYP2B6; to a lesser extent by CYP2C9 and CYP2C19.¹ ¹³ ¹⁴ ²² ²³ ³⁰ Not likely to inhibit CYP isoenzymes 1A2, 2C9, 2C19, 2D6 or 3A4 nor induce isoenzymes 1A2 or 3A4.¹ ¹³ Weak inhibitor of CYP2B6.¹ ²⁵

Does not inhibit P-glycoprotein (Pgp) transport system.¹

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Clinically important interactions mediated by CYP enzymes unlikely.¹ ¹³ ²⁵

CYP3A4 inhibitors: No substantial effect on systemic exposure or antiplatelet activity of prasugrel’s active metabolite.¹ ²²

CYP3A4 inducers: Not expected to substantially alter pharmacokinetic or pharmacodynamic response to prasugrel.¹ ²⁵

Drugs metabolized by CYP2B6: Potential for increased plasma concentrations and exposure to concomitantly administered drug; however, clinically important interactions not expected because of weak inhibition of CYP2B6.¹ ²⁵

Other Antiplatelet or Antithrombotic Agents

Manufacturer states that prasugrel may be administered concomitantly with aspirin, heparin, and GP IIb/IIIa-receptor inhibitors.¹ While evidence from drug interaction studies with other antiplatelet or antithrombotic agents generally is lacking, increased risk of bleeding likely with concomitant use of such agents.¹³ ¹⁴

Specific Drugs or Foods

Drug	Interaction	Comments
Aspirin	Possible increased bleeding time and greater levels of platelet inhibition¹ ²⁶	May be administered concomitantly¹
Carbamazepine	Pharmacokinetic/pharmacodynamic response to prasugrel not expected to be substantially altered¹ ²⁵
Ciprofloxacin	Systemic exposure and antiplatelet activity of prasugrel active metabolite not affected¹ ²²
Clarithromycin	Systemic exposure and antiplatelet activity of prasugrel active metabolite not affected¹ ²²
Cyclophosphamide	Possible increased plasma concentrations and exposure to concomitant drug; clinically important interaction not expected¹ ²⁵
Digoxin	Concurrent administration not expected to affect digoxin clearance¹	May be administered concomitantly¹
Diltiazem	Systemic exposure and antiplatelet activity of prasugrel active metabolite not affected¹ ²²
Grapefruit juice	Systemic exposure and antiplatelet activity of prasugrel active metabolite not affected¹ ²²
Halothane	Possible increased plasma concentrations and exposure to concomitant drug; clinically important interaction not expected¹
Heparin	Possible increased bleeding time, but no associated changes in coagulation or platelet inhibition¹	May be administered concomitantly¹
HMG-CoA reductase inhibitors (e.g., atorvastatin)	Minor effect on exposure to active prasugrel metabolite, but no effect on inhibition of platelet aggregation¹ ¹⁷ ²³	May be used concomitantly; no dosage adjustments necessary.¹ ²³
Histamine H₂-receptor antagonists (e.g., ranitidine )	Decreased plasma concentrations of active prasugrel metabolite by approximately 14%, but systemic exposure unaffected	May be administered concomitantly¹
Indinavir	Systemic exposure and antiplatelet activity of prasugrel active metabolite not affected¹ ²²
Ketoconazole	Decreased plasma concentrations of prasugrel’s active metabolite by 34–46%; no change in systemic exposure or platelet inhibition¹ ¹⁴ ¹⁷ ²²
Nevirapine	Possible increased plasma concentrations and exposure to concomitant drug; clinically important interaction not expected¹ ²⁵
NSAIAs	Increased risk of bleeding with concomitant long-term use of NSAIAs¹
Propofol	Possible increased plasma concentrations and exposure to concomitant drug; clinically important interaction not expected¹ ²⁵
Proton-pump inhibitors (e.g., lansoprazole)	Possible decreased systemic exposure and peak plasma concentrations of prasugrel’s active metabolite, but no effect on platelet inhibition¹ ¹³ ¹⁷ ²⁴	May be administered concomitantly¹
Rifampin	Pharmacokinetic/pharmacodynamic response to prasugrel not expected to be substantially altered¹ ²⁵
Thrombolytic agents	Increased risk of bleeding¹
Warfarin	Increased risk of bleeding; prolonged bleeding time observed with concomitant use¹

Prasugrel Pharmacokinetics

Absorption

Bioavailability

Rapidly and completely absorbed following oral administration.¹ ¹³ ²⁷ ²⁸ ⁶²

Onset

Peak plasma concentrations of active metabolite attained approximately 30 minutes following oral administration; no evidence of accumulation with repeated administration.¹ ¹³ ²⁵ ²⁸

Following a 60-mg loading dose, approximately 90% of patients achieve at least 50% inhibition of platelet aggregation by 1 hour; maximum platelet inhibition was approximately 80%.¹ Steady-state platelet inhibition (70%) occurs within 3–5 days following maintenance therapy with repeated dosages of 10 mg daily.¹

Duration

Following discontinuance, platelet aggregation gradually returns to baseline values in about 5–9 days.¹

Food

In healthy individuals, food (high-fat or high-caloric meal) decreased peak plasma concentrations by 49% but did not alter exposure to active metabolite.¹

Special Populations

In patients with end-stage renal impairment, exposure to active metabolite was decreased to approximately half that in healthy individuals and those with moderate renal impairment.¹

In low-weight individuals (weight <60 kg), increased exposure to active metabolite observed.¹ Clearance of active metabolite appears to increase exponentially with increasing body weight.³⁰

In patients ≥75 years of age, mean exposure to active metabolite increased by 19% compared with younger patients.¹

Distribution

Plasma Protein Binding

Approximately 98% for active metabolite.¹

Elimination

Metabolism

Rapidly hydrolyzed by esterases to an inactive thiolactone; subsequently metabolized to active metabolite by CYP isoenzymes (primarily by 3A4 and 2B6, and to a lesser extent by 2C9 and 2C19).¹ ¹³ ¹⁴ ²² ²³ ²⁸ ³⁰ Requires a single step for metabolic activation compared with clopidogrel, which undergoes a 2-step oxidative process.¹³ ¹⁴ ²² ²⁹ ³⁰ ³¹

Elimination Route

Excreted in urine (68%) and feces (27%) as inactive metabolites.¹ ¹⁴ ²⁸ Active metabolite not expected to be removed by dialysis.¹

Half-life

Manufacturer reports half-life of active metabolite about 7 hours (range 2–15 hours);¹ half-life of about 3.7 hours also reported.¹³ ¹⁴

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹ Dispense and store in original container; keep container closed and do not remove dessicant from bottle.¹

Actions

Prodrug; platelet inhibitory activity is dependent on hepatic transformation to an active metabolite.¹ ² ¹⁴ ²² ³⁰ ³¹

Active metabolite binds irreversibly to P2Y12 class of ADP receptors on platelet surfaces, thereby inhibiting ADP-dependent platelet activation and aggregation.¹ ¹³ ¹⁴ ¹⁵

ADP receptor is irreversibly modified; platelets exposed to prasugrel remain affected for the remainder of their lifespan (about 7–10 days).¹ ²²

Prasugrel is a thienopyridine derivative that is structurally and pharmacologically related to clopidogrel.¹ ² ³ ⁴ ⁵ ⁶ ⁸ ¹³ ¹⁴ ¹⁵ ²⁸ ³⁰ Exhibits more rapid, consistent, and greater inhibition of ADP-mediated platelet aggregation than clopidogrel.² ³ ⁸ ⁹ ¹¹ ¹² ¹³ ¹⁴ ¹⁵ ²⁷ Increased potency appears to be a result of more efficient conversion of the prodrug to its active metabolite.² ³ ⁹ ¹⁴ ¹⁵ ²² ²⁷ ³⁰

Genetic polymorphisms of CYP isoenzymes (e.g., CYP2B6, CYP2C9, CYP2C19, CYP3A5) do not appear to affect pharmacologic or clinical response to prasugrel.¹ ²⁹

Advice to Patients

Importance of counseling patients about potential risks versus benefits of prasugrel.¹

Importance of informing patients that they will bruise and/or bleed more easily and that a longer than usual time will be required to stop bleeding when taking prasugrel.¹ Importance of informing clinicians about any unexpected, prolonged, or excessive bleeding, or blood in urine or stool.¹

Importance of patients taking prasugrel exactly as prescribed and not discontinuing therapy without first consulting the prescribing clinician.¹

Importance of informing clinicians (e.g., physicians, dentists) about prasugrel therapy before any invasive procedure or surgery is scheduled.¹ ⁴⁵ Clinician performing invasive procedure should consult with prescribing clinician before discontinuing prasugrel.¹ ⁴⁵

Risk of thrombotic thrombocytopenic purpura (TTP); importance of advising patients to immediately seek medical attention if they experience manifestations such as fever, weakness, extreme skin paleness, purple skin patches, yellowing of the skin or eyes, or otherwise unexplained neurologic changes.¹

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, particularly drugs that affect bleeding (e.g., warfarin, NSAIAs).¹

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Prasugrel Hydrochloride
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	5 mg (of prasugrel)	Effient	Eli Lilly and Company (also promoted by Daiichi Sankyo, Inc.)
		10 mg (of prasugrel)	Effient	Eli Lilly and Company (also promoted by Daiichi Sankyo, Inc.)

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Effient 10MG Tablets (LILLY): 30/$215.26 or 90/$608.03

Effient 5MG Tablets (LILLY): 30/$218.00 or 90/$622.00

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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43. Pfisterer M, Brunner-La Rocca HP, Buser PT et al. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents. JACC. 2006; 48:2584-91. [PubMed 17174201]

44. Eisenstein EL, Anstrom KJ, Kong DF et al. Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation. JAMA. 2007;297:159-168.

45. Grines CL, Bonow RO, Casey DE et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stenosis. A science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. Circulation. 2007; 115:813-8. [PubMed 17224480]

46. Kereiakes DJ. Does clopidogrel each day keep stent thrombosis away? JAMA. 2007; 297:209-11. Editorial.

47. Spertus JA, Kettelkamp R, Vance C et al. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement. Results from the PREMIER registry. Circulation. 2006; 113:2803-9. [PubMed 16769908]

48. Jeremias A, Sylvia B, Bridges J et al. Stent thrombosis after successful sirolimus-eluting stent implantation. Circulation. 2004 109:1930-2.

49. Ong ATL, McFadden EP, Regar E et al. Late angiographic stent thrombosis (LAST) events with drug-eluting stents. JACC. 2005; 45:2088-92. [PubMed 15963413]

54. Luscher TF, Steffel J, Eberli FR et al. Drug-eluting stent and co

Sunday, 20 May 2012

Novahistine Elixir

Pronunciation: klor-fen-IR-a-meen/fen-il-EF-rin
Generic Name: Chlorpheniramine/Phenylephrine
Brand Name: Examples include Novahistine and Triaminic Cold/Allergy

Novahistine Elixir is used for:

Relieving symptoms of sinus congestion, sinus pressure, runny nose, and sneezing due to colds, upper respiratory infections, and allergies. It may also be used for other conditions as determined by your doctor.

Novahistine Elixir is an antihistamine and decongestant combination. The antihistamine works by blocking the action of histamine, which helps reduce symptoms such as watery eyes and sneezing. The decongestant promotes sinus and nasal drainage, relieving congestion and pressure.

Do NOT use Novahistine Elixir if:

you are allergic to any ingredient in Novahistine Elixir

you have severe high blood pressure, severe heart blood vessel disease, rapid heartbeat, or severe heart problems

you take sodium oxybate (GHB) or you have taken furazolidone or a monoamine oxidase (MAO) inhibitor (eg, phenelzine) within the last 14 days

Contact your doctor or health care provider right away if any of these apply to you.

Before using Novahistine Elixir:

Some medical conditions may interact with Novahistine Elixir. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding

if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

if you have allergies to medicines, foods, or other substances

if you have a fast, slow, or irregular heartbeat

if you have a history of asthma; lung problems (eg, emphysema); adrenal gland problems (eg, adrenal gland tumor); heart problems; high blood pressure; diabetes; heart blood vessel problems; stroke; glaucoma; a blockage of your stomach, intestines, or bladder; ulcers; trouble urinating; an enlarged prostate; seizures; or an overactive thyroid

Some MEDICINES MAY INTERACT with Novahistine Elixir. Tell your health care provider if you are taking any other medicines, especially any of the following:

Digoxin or droxidopa because the risk of irregular heartbeat or heart attack may be increased

Beta-blockers (eg, propranolol), catechol-O-methyltransferase (COMT) inhibitors (eg, tolcapone), furazolidone, indomethacin, MAO inhibitors (eg, phenelzine), sodium oxybate (GHB), or tricyclic antidepressants (eg, amitriptyline) because they may increase Novahistine Elixir's risk of side effects

Bromocriptine or hydantoins (eg, phenytoin) because their risk of side effects may be increased by Novahistine Elixir

Guanadrel, guanethidine, mecamylamine, methyldopa, or reserpine because their effectiveness may be decreased by Novahistine Elixir

This may not be a complete list of all interactions that may occur. Ask your health care provider if Novahistine Elixir may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Novahistine Elixir:

Use Novahistine Elixir as directed by your doctor. Check the label on the medicine for exact dosing instructions.

Novahistine Elixir may be taken with or without food.

Use a measuring device marked for medicine dosing. Ask your pharmacist for help if you are unsure of how to measure your dose.

If you miss a dose of Novahistine Elixir, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Novahistine Elixir.

Important safety information:

Novahistine Elixir may cause drowsiness, dizziness, or blurred vision. These effects may be worse if you take it with alcohol or certain medicines. Use Novahistine Elixir with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.

Do not take diet or appetite control medicines while you are taking Novahistine Elixir without checking with you doctor.

Do NOT take more than the recommended dose or use for longer than prescribed without checking with your doctor.

If your symptoms do not get better within 5 to 7 days or if they get worse, check with your doctor.

Novahistine Elixir may cause you to become sunburned more easily. Avoid the sun, sunlamps, or tanning booths until you know how you react to Novahistine Elixir. Use a sunscreen or wear protective clothing if you must be outside for more than a short time.

Novahistine Elixir may interfere with skin allergy tests. If you are scheduled for a skin test, talk to your doctor. You may need to stop taking Novahistine Elixir for a few days before the tests.

Tell your doctor or dentist that you take Novahistine Elixir before you receive any medical or dental care, emergency care, or surgery.

Use Novahistine Elixir with caution in the ELDERLY; they may be more sensitive to its effects.

Caution is advised when using Novahistine Elixir in CHILDREN; they may be more sensitive to its effects.

PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Novahistine Elixir while you are pregnant. It is not known if Novahistine Elixir is found in breast milk. If you are or will be breast-feeding while you use Novahistine Elixir, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Novahistine Elixir:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Constipation; diarrhea; dizziness; drowsiness; excitability; headache; loss of appetite; nausea; nervousness or anxiety; trouble sleeping; upset stomach; vomiting; weakness.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); difficulty urinating or inability to urinate; fast or irregular heartbeat; hallucinations; seizures; severe dizziness, lightheadedness, or headache; tremor; vision changes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Novahistine side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include blurred vision; confusion; hallucinations; seizures; severe dizziness, lightheadedness, or headache; severe drowsiness; unusually fast, slow, or irregular heartbeat; vomiting.

Proper storage of Novahistine Elixir:

Store Novahistine Elixir at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Novahistine Elixir out of the reach of children and away from pets.

General information:

If you have any questions about Novahistine Elixir, please talk with your doctor, pharmacist, or other health care provider.

Novahistine Elixir is to be used only by the patient for whom it is prescribed. Do not share it with other people.

If your symptoms do not improve or if they become worse, check with your doctor.

Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Novahistine Elixir. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

More Novahistine resources

Novahistine Side Effects (in more detail)
Novahistine Use in Pregnancy & Breastfeeding
Novahistine Drug Interactions
Novahistine Support Group
0 Reviews for Novahistine - Add your own review/rating

Actifed Cold & Allergy Concise Consumer Information (Cerner Multum)

Histatab Plus Concise Consumer Information (Cerner Multum)

Rynatan Prescribing Information (FDA)

Sonahist Prescribing Information (FDA)

Compare Novahistine with other medications

Cold Symptoms
Hay Fever

Methadone Diskets

Pronunciation: METH-a-done
Generic Name: Methadone
Brand Name: Methadone Diskets

Methadone Diskets may cause severe and sometimes fatal heart and breathing problems. These problems may occur some time after you take a dose. Tell your doctor right away if you develop any new or worsening symptoms such as slowed or shallow breathing or irregular heartbeat. Your doctor will perform heart and lung function tests to check for side effects while you take Methadone Diskets. Keep all doctor and laboratory appointments. Talk with your doctor and be sure you understand the risks and benefits of using Methadone Diskets.

Do not take more than the recommended dose or take Methadone Diskets more often than prescribed. This can lead to overdose and possible death.

Methadone Diskets is used for:

Treating narcotic addiction as part of a treatment program. It may also be used for other conditions as determined by your doctor.

Methadone Diskets is a narcotic analgesic. It works by acting on opiate pain receptors in the brain and on smooth muscle to provide pain relief.

Do NOT use Methadone Diskets if:

you are allergic to any ingredient in Methadone Diskets

you have slowed breathing or severe asthma, or if you are having an asthma attack

you have a stomach or bowel blockage or certain severe bowel problems (eg, paralytic ileus)

you have diarrhea caused by food poisoning or antibiotic use

you are taking sodium oxybate (GHB)

you have taken a monoamine oxidase inhibitor type B (MAOI-B) (eg, rasagiline, selegiline) within the last 14 days

Contact your doctor or health care provider right away if any of these apply to you.

Before using Methadone Diskets:

Some medical conditions may interact with Methadone Diskets. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding

if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

if you have allergies to medicines, foods, or other substances

if you have lung or breathing problems (eg, asthma), chronic obstructive pulmonary disease (COPD), sleep apnea, stomach or bowel problems (eg, bowel inflammation), stomach pain or constipation, liver or kidney problems, thyroid problems, or Addison disease

if you have abnormal curvature of the spine; narrowing of the urethra, trouble urinating, or an enlarged prostate; low blood volume, blood pressure, or blood oxygen levels; low potassium or magnesium blood levels; increased pressure, tumors, or lesions in your head; a recent head injury; or seizures

if you have a history of heart problems (eg, enlarged heart) or irregular heartbeat

if you or a family member have a history of mental or mood problems (eg, anxiety, depression), suicidal thoughts or attempts, or alcohol or substance abuse

if you are elderly, very ill, or very overweight, or if you have recently had stomach or intestine surgery

Some MEDICINES MAY INTERACT with Methadone Diskets. Tell your health care provider if you are taking any other medicines, especially any of the following:

Barbiturate anesthetics (eg, thiopental), benzodiazepines (eg, midazolam), cimetidine, MAOI-B (eg, rasagiline, selegiline), other narcotic analgesics (eg, morphine), phenothiazines (eg, promethazine), or sodium oxybate (GHB) because side effects such as sedation and slowed breathing may occur

Antiarrhythmics (eg, amiodarone, dofetilide, flecainide, propafenone), antipsychotics (eg, haloperidol, paliperidone, ziprasidone), calcium channel blockers (eg, nifedipine), certain antiemetics (eg, dolasetron, droperidol), chloroquine, cisapride, diuretics (eg, furosemide), H₁ antagonists (eg, astemizole), kinase inhibitors (eg, lapatinib, nilotinib), lithium, macrolide antibiotics (eg, clarithromycin), phenothiazines (eg, chlorpromazine), quinolones (eg, ciprofloxacin), streptogramins (eg, quinupristin), tacrolimus, or tricyclic antidepressants (eg, desipramine) because the risk of QT prolongation may be increased

Azole antifungals (eg, fluconazole, ketoconazole, voriconazole) or certain selective serotonin reuptake inhibitors (SSRIs) (eg, fluvoxamine, sertraline) because they may increase the risk of Methadone Diskets's side effects

Abacavir, carbamazepine, efavirenz, HIV protease inhibitors (eg, amprenavir, lopinavir, nelfinavir, ritonavir), narcotic agonists/antagonists (eg, butorphanol, nalbuphine, pentazocine), narcotic antagonists (eg, naloxone, naltrexone), nevirapine, phenobarbital, phenytoin, rifampin, or St. John's wort because they may decrease Methadone Diskets's effectiveness

Zidovudine because the risk of its side effects may be increased by Methadone Diskets

Nucleoside reverse transcriptase inhibitors (NRTIs) (eg, abacavir, didanosine, stavudine) because their effectiveness may be decreased by Methadone Diskets

This may not be a complete list of all interactions that may occur. Ask your health care provider if Methadone Diskets may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Methadone Diskets:

Use Methadone Diskets as directed by your doctor. Check the label on the medicine for exact dosing instructions.

Take Methadone Diskets by mouth with or without food.

Do not chew or swallow the tablet. Place the tablet in a glass and add about 4 oz/120 mL of cold water, orange juice, or other acidic fruit beverage. Allow the tablet to dissolve completely, then drink all of the liquid. Rinse the container with an additional small amount of fluid and drink the contents to ensure the entire dose is taken. Methadone Diskets is for oral use only and must not be injected.

The initial dose of Methadone Diskets must be administered under close medical supervision.

Take Methadone Diskets on a regular schedule to get the most benefit from it.

If Methadone Diskets is no longer needed, dispose of it as soon as possible. Ask your doctor or pharmacist how to dispose of it properly.

Always keep Methadone Diskets in a secure place to protect from theft.

If you miss a dose of Methadone Diskets, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once. If you miss your doses of Methadone Diskets for more than 2 days, contact your doctor before you begin taking Methadone Diskets again.

Ask your health care provider any questions you may have about how to use Methadone Diskets.

Important safety information:

Methadone Diskets may cause drowsiness, dizziness, blurred vision, or lightheadedness. These effects may be worse if you take it with alcohol or certain medicines. Use Methadone Diskets with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.

Do not drink alcohol or use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using Methadone Diskets; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.

Methadone Diskets may cause dizziness, lightheadedness, or fainting; alcohol, hot weather, exercise, or fever may increase these effects. To prevent them, sit up or stand slowly, especially in the morning. Sit or lie down at the first sign of any of these effects.

Breathing problems may occur some time after you take a dose of Methadone Diskets. Tell your doctor or seek medical care immediately if you notice trouble breathing (eg, slowed or shallow breathing) while you take Methadone Diskets

Methadone Diskets may cause constipation. Constipation may be avoided by using a stool softener or fiber laxative.

The risk of Methadone Diskets becoming habit-forming may be greater if you take it in high doses or for a long time. Do NOT take more than the recommended dose or use for longer than prescribed without checking with your doctor.

Tell your doctor or dentist that you take Methadone Diskets before you receive any medical or dental care, emergency care, or surgery.

Lab tests, including liver function, lung function, and heart function, may be performed while you use Methadone Diskets. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.

Use Methadone Diskets with caution in the ELDERLY; they may be more sensitive to its effects.

Methadone Diskets should not be used in CHILDREN; safety and effectiveness in children have not been confirmed.

PREGNANCY and BREAST-FEEDING: Methadone Diskets may cause harm to the fetus. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Methadone Diskets while you are pregnant. Methadone Diskets is found in breast milk. If you are or will be breast-feeding while you use Methadone Diskets, check with your doctor. Discuss any possible risks to your baby.

When used for long periods of time or at high doses, Methadone Diskets may not work as well and may require higher doses to obtain the same effect as when originally taken. This is known as TOLERANCE. Talk with your doctor if Methadone Diskets stops working well. Do not take more than prescribed.

Some people who use Methadone Diskets for a long time may develop a need to continue taking it. People who take high doses are also at risk. This is known as DEPENDENCE or addiction.

If you suddenly stop taking Methadone Diskets, you may experience WITHDRAWAL symptoms including anxiety; diarrhea; fever, runny nose, or sneezing; goose bumps and abnormal skin sensations; nausea; vomiting; pain; rigid muscles; rapid heartbeat; seeing, hearing or feeling things that are not there; shivering or tremors; sweating; and trouble sleeping.

Possible side effects of Methadone Diskets:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Constipation; dizziness; drowsiness; dry mouth; headache; increased sweating; itching; lightheadedness; nausea; vomiting; weakness.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); confusion; decreased sexual desire or ability; excessive drowsiness; fainting; fast, slow, or irregular heartbeat; hallucinations; loss of appetite; menstrual changes; mental or mood changes (eg, agitation, disorientation, exaggerated sense of well-being); seizures; severe or persistent dizziness or lightheadedness; shortness of breath; slow or shallow breathing; swelling of the arms, feet, or legs; trouble sleeping; trouble urinating; unusual bruising or bleeding.

See also: Methadone Diskets side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include cold and clammy skin; coma; fainting; fast, slow, or irregular heartbeat; muscle weakness; pinpoint pupils, severe dizziness, drowsiness, or lightheadedness; slow, shallow, or difficult breathing.

Proper storage of Methadone Diskets:

Store Methadone Diskets between 68 and 77 degrees F (20 and 25 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Methadone Diskets out of the reach of children and away from pets.

General information:

If you have any questions about Methadone Diskets, please talk with your doctor, pharmacist, or other health care provider.

Methadone Diskets is to be used only by the patient for whom it is prescribed. Do not share it with other people.

If your symptoms do not improve or if they become worse, check with your doctor.

Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Methadone Diskets. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

More Methadone Diskets resources

Methadone Diskets Side Effects (in more detail)
Methadone Diskets Use in Pregnancy & Breastfeeding
Methadone Diskets Drug Interactions
Methadone Diskets Support Group
10 Reviews for Methadone Diskets - Add your own review/rating

Compare Methadone Diskets with other medications

Opiate Withdrawal
Pain

Saturday, 19 May 2012

Phentolamine Mesylate

Class: Non-selective alpha-Adrenergic Blocking Agents
VA Class: AU200
CAS Number: 65-28-1
Brands: Regitine, Vasomax, Z-Max

Introduction

α-adrenergic blocking agent, an imidazoline.¹⁷⁷ ^a

Uses for Phentolamine Mesylate

Diagnosis of Pheochromocytoma

Used as an aid in the diagnosis of pheochromocytoma.^a ¹⁷⁷

Determination of blood catecholamine concentrations, urinary assay of catecholamines, or other biochemical assays are the safest and most reliable diagnostic methods and they have largely replaced phentolamine and other pharmaceutical tests.¹⁷⁷ ^a No test, however, is completely reliable.¹⁷⁷ ^a

May be used when additional confirmatory evidence of pheochromocytoma is required and potential benefits outweigh the possible risks.¹⁷⁷ ^a

Test is more reliable with sustained than with paroxysmal hypertension; no diagnostic value in absence of hypertension at the time of the test.¹⁷⁷ ^a

Sudden and marked reduction in BP following parenteral administration of phentolamine suggests pheochromocytoma;^a however, false-negative and false-positive responses are frequent.¹⁷⁷ ^a

Hypertension in Pheochromocytoma

May be administered immediately prior to or during pheochromocytomectomy to prevent or control paroxysmal hypertension resulting from anesthesia, stress, or operative manipulation of the tumor.^a

Has been used to manage pheochromocytoma until surgery is performed and for prolonged treatment of hypertension when the tumor is not operable; however, phenoxybenzamine is considered the drug of choice because it has a longer duration of action.^a

Hypertensive Crises

Has been used to treat hypertensive crises caused by sympathomimetic amines† (e.g., methoxamine, phenylephrine) or catecholamine excess by certain foods or drugs in patients taking MAO inhibitors† (e.g., isocarboxazid [no longer commercially available in the US], tranylcypromine), or by clonidine withdrawal syndrome†.^a ¹⁸⁰

If used, the initial goal is to reduce mean arterial BP by no more than 25% within minutes to 1 hour, followed by further reduction if stable toward 160/100 to 110 mm Hg within the next 2–6 hours, avoiding excessive declines in pressure that could precipitate renal, cerebral, or coronary ischemia.¹⁶⁴

If this BP is well tolerated and the patient is clinically stable, may implement further gradual reductions toward normal in the next 24–48 hours.^a In patients with aortic dissection, reduce systolic BP to <100 mm Hg if tolerated.^a

Extravasation of Catecholamines

Used to prevent dermal necrosis and sloughing following IV administration or extravasation of norepinephrine.¹⁷⁷ ¹⁸⁰ ^a

Has been used to prevent necrosis after extravasation of dopamine†.^a

MI

Has been used to decrease impedance to left ventricular ejection and the infarct size in patients with MI associated with left ventricular failure†.^a

However, contraindicated in patients with MI,¹⁷⁷ ^a and investigators do not recommend for routine use, since left ventricular function and the ECG must be monitored continuously.^a

Erectile Dysfunction

Self-injection of small doses combined with papaverine hydrochloride into the corpus cavernosum has been effective for the treatment of erectile dysfunction† (ED, impotence).¹⁰³ ¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹¹⁰ ¹¹² ¹¹³ ¹¹⁴ ¹¹⁵ ¹¹⁶ ¹¹⁷ ¹¹⁸ ¹¹⁹ ¹²⁰ ¹²¹ ¹²² ¹²³ ¹²⁴ ¹²⁵ ¹²⁶ ¹²⁷

Combination has been effective in patients with neurogenic¹⁰³ ¹⁰⁵ ¹⁰⁶ ¹⁰⁸ ¹¹⁰ ¹¹² ¹¹³ ¹¹⁵ ¹¹⁶ ¹¹⁸ ¹¹⁹ ¹²⁰ ¹²² ¹²³ ¹²⁴ ¹²⁷ and/or limited vasculogenic impotence¹⁰³ ¹⁰⁵ ¹⁰⁶ ¹⁰⁸ ¹¹⁰ ¹¹² ¹¹³ ¹¹⁵ ¹¹⁶ ¹²⁰ ¹²² ¹²³ ¹²⁴ ¹²⁷ or with psychogenic impotence,¹⁰⁵ ¹⁰⁶ ¹⁰⁸ ¹²³ ¹²⁴ ¹²⁷ but efficacy in those with a vasculogenic component of their impotence may be variable depending on the extent and type of vascular dysfunction.¹⁰³ ¹⁰⁸ ¹¹⁰ ¹¹⁵ ¹²⁰ ¹²³ ¹²⁴

Erection, which can be potentiated by sexual arousal, usually occurs within 10 minutes after injection of the drugs and may persist for 1 to several hours;¹⁰⁵ ¹⁰⁶ ¹⁰⁸ ¹¹³ ¹¹⁴ ¹¹⁶ ¹¹⁸ ¹¹⁹ ¹²⁴ tolerance to the drugs may occur during long-term use;¹⁰⁵ ¹¹⁴ ¹²⁴ priapism may occur.¹⁰³ ¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹¹⁰ ¹¹³ ¹¹⁵ ¹¹⁶ ¹²⁴ ¹²⁵ ¹²⁶ ¹²⁷

Cocaine-induced Acute Coronary Syndrome

Used as an adjunct in the management of cocaine overdose† to reverse coronary vasoconstriction¹⁷⁵ ¹⁸⁰ following use of oxygen, benzodiazepines (e.g., diazepam, lorazepam), and nitroglycerin.¹⁷⁵

Phentolamine Mesylate Dosage and Administration

General

Diagnosis of Pheochromocytoma

Withhold sedatives, analgesics (e.g., opiates), and all other medications except essential drugs (e.g., digitalis, insulin) for at least 24 hours (preferably 48-72 hours) prior to the test.¹⁷⁷

Withhold antihypertensive drugs until BP returns to untreated hypertensive levels.¹⁷⁷

Before injection, the patient should rest in a supine position (preferably in a quiet, darkened room) until the BP is stabilized; read BP every 10 minutes for at least 30 minutes to establish basal BP.¹⁷⁷ ^a

After insertion of needle, delay IV injection until venipuncture effect on blood pressure has passed; then inject rapidly.¹⁷⁷ ^a

After IV injection, record BP immediately (at 30-second intervals for the first 3 minutes, then 1-minute intervals for the next 7 minutes).¹⁷⁷ ^a

After IM administration, determine BP at 5-minute intervals for 30-45 minutes.^a

Typical BP response in patients with pheochromocytoma is a decrease of 60 mm Hg systolic and 25 mm Hg diastolic within 2 minutes after IV administration or 20 minutes after IM administration.¹⁷⁷ ^a BP usually returns to pretest levels within 15–30 minutes or 3–4 hours, following IV¹⁷⁷ or IM administration, respectively.^a

Positive response/test is a BP decrease ≥35 mm Hg systolic and 25 mm Hg diastolic;^a negative response is when BP is unchanged, elevated, or lowered <35 mm Hg systolic and 25 mm Hg diastolic.¹⁷⁷ ^a

Confirm positive response by other diagnostic procedures, preferably by measurement of urinary catecholamines or their metabolites.¹⁷⁷

Administration

Administer usually by IV or IM injection; also may be administered by IV infusion.¹⁷⁷ ^a Has been administered by intracavernous injection† for the treatment of impotence.¹⁰³ ¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹¹⁰ ¹¹² ¹¹³ ¹¹⁴ ¹¹⁵

IV administration

Reconstitution

Reconstitute vial containing 5 mg of lyophilized drug with 1 mL of sterile water to provide solution containing 5 mg of phentolamine mesylate per mL.¹⁷⁷ ^a

Dilution

IV infusion: for prevention of tissue necrosis and sloughing following extravasation or IV administration of norepinephrine, may add reconstituted phentolamine mesylate to each L of solution containing norepinephrine.¹⁷⁷ ^a

Rate of Administration

IV injection for pheochromocytoma test: inject rapidly.¹⁷⁷ ^a

IM Administration

Reconstitution

Reconstitute vial containing 5 mg of lyophilized drug with 1 mL of sterile water to provide solution containing 5 mg of phentolamine mesylate per mL.¹⁷⁷ ^a

Local Infiltration

Reconstitution

Reconstitute vial containing 5 mg of lyophilized drug with 1 mL of sterile water to provide solution containing 5 mg of phentolamine mesylate per mL.¹⁷⁷ ^a

Dilution

For treatment or prevention of tissue necrosis and sloughing following extravasation of catecholamines, dilute the appropriate amount of reconstituted phentolamine mesylate in 10–15 mL of 0.9% sodium chloride injection.¹⁷⁷ ^a

Dosage

Available as phentolamine mesylate; dosage expressed in terms of phentolamine mesylate.¹⁷⁷ ^a

Pediatric Patients

Diagnosis of Pheochromocytoma

IV (Preferred Route)

1 mg,¹⁷⁷ ^a 0.1 mg/kg, or 3 mg/m².^a

IM

3 mg.¹⁷⁷ ^a

Hypertension in Pheochromocytoma

Pheochromocytomectomy

Preoperative: 1 mg,¹⁷⁷ ^a 0.1 mg/kg, or 3 mg/m², 1–2 hours before surgery; may repeat if necessary.^a

During surgery: 1mg,¹⁷⁷ ^a 0.1 mg/kg, or 3 mg/m².^a

Postoperative: may administer norepinephrine to control hypotension (usually following complete pheochromocytoma removal);¹⁷⁷ however, hypotension is prevented more frequently by administration of blood, plasma, or 5% albumin in 0.9% sodium chloride injection to correct the reduced blood volume.^a

Preoperative: 1mg,¹⁷⁷ ^a 0.1 mg/kg, or 3 mg/m², 1–2 hours before surgery; may repeat if necessary.^a

Extravasation of Catecholamines

Dopamine Extravasation

Local Infiltration

Prevention of tissue necrosis and sloughing: 0.1–0.2 mg/kg (maximum 10 mg per dose).^a

Immediate and conspicuous local hyperemic changes occur if the area is infiltrated within 12 hours.^a

Adults

Diagnosis of Pheochromocytoma

IV (Preferred Route) or IM

5 mg.¹⁷⁷ ^a

Hypertension in Pheochromocytoma

Hypertensive Crises Secondary to Catecholamine Excess

Usually 5–15 mg.^a

Pheochromocytomectomy

Preoperative: 5 mg, 1-2 hours before surgery; repeat if necessary.¹⁷⁷ ^a

During surgery, to prevent or control paroxysms of hypertension, tachycardia, respiratory depression, convulsions, or other effects of excessive epinephrine secretion due to manipulation of the tumor: 5 mg as needed.¹⁷⁷ ^a

IM

Preoperative: 5 mg, 1-2 hours before surgery; repeat if necessary.¹⁷⁷ ^a

Hypertensive Crises†

IV

5–15 mg has been used.^a

Extravasation of Catecholamines

IV Administration or Extravasation of Norepinephrine

Local Infiltration

Treatment of tissue necrosis and sloughing: 5–10 mg (in 10–15 mL of 0.9% sodium chloride) into affected area.¹⁷⁷ ¹⁸⁰ ^a

Immediate and conspicuous local hyperemic changes occur if the area is infiltrated within 12 hours; ineffective if used >12 hours after extravasation.¹⁷⁷ ^a

IV Infusion

Prevention of tissue necrosis and sloughing: 10 mg added to each liter of IV fluid containing norepinephrine; pressor effect of norepinephrine is unaffected.¹⁷⁷ ^a

Extravasation of Dopamine Injection†

Local Infiltration

Prevention of tissue necrosis and sloughing: 5–10 mg (in 10–15 mL of 0.9% sodium chloride) infiltrated (using a syringe with a fine hypodermic needle) liberally throughout the affected area.^a

Immediate and conspicuous local hyperemic changes occur if the area is infiltrated within 12 hours.^a

MI†

IV Infusion

For treatment of left ventricular failure secondary to acute MI†, dosages of 0.17–0.4 mg/minute have been used.^a

Erectile Dysfunction†

Intracavernosal Self-injection

Usually 0.5–1 mg (range: 0.08–1.25 mg) combined with papaverine hydrochloride 2.5–37.5 mg has been effective. ^a

Tolerance with long-term use may require dosage increase.¹⁰⁵ ¹¹⁴ ¹²⁴

Prescribing Limits

Pediatric Patients

Extravasation of Catecholamines

Dopamine Extravasation

Local Infiltration

Maximum 10 mg per dose.^a

Cautions for Phentolamine Mesylate

Contraindications

MI or history of MI.¹⁷⁷ ^a However, results of some studies indicate that the drug may have a beneficial effect in patients with MI.^a

Coronary insufficiency, angina, or other evidence suggestive of CAD.¹⁷⁷ ^a

Known hypersensitivity to phentolamine, related compounds, or any ingredient in the formulation.¹⁷⁷ ^a

Warnings/Precautions

Warnings

Cardiovascular Effects

Risk of MI, cerebrovascular spasm or occlusion, usually in association with marked hypotension.¹⁷⁷ ^a

Risk of tachycardia, cardiac arrhythmias; defer cardiac glycoside administration until cardiac rhythm returns to normal.¹⁷⁷

Risk of severe hypotension or other signs and symptoms of shock; treat with prompt supportive measures and norepinephrine (if necessary).^a Do not administer epinephrine for hypotension since it may cause a paradoxical fall in BP.^a

Diagnostic Tests for Pheochromocytoma

Phentolamine and other pharmaceutical tests no longer procedures of choice for diagnosis of pheochromocytoma; may be used when additional confirmatory evidence of pheochromocytoma is required and the potential benefits of the tests outweigh the possible risks.¹⁷⁷ ^a Urinary assay of catecholamines or other biochemical assays are the safest and most reliable methods.¹⁷⁷ ^a Consider that no test is completely reliable.¹⁷⁷ ^a

Possible false-negative responses to phentolamine test (e.g., in patients with paroxysmal hypertension or with a pheochromocytoma not secreting enough epinephrine or norepinephrine to elevate BP or sustain an elevation).^a

False-positive reactions (occurring more commonly than false-negative) reported in patients with essential hypertension, uremia, or in those who received sedatives, opiates, or antihypertensive drugs.^a (See Specific Drugs under Interactions.)

Do not perform test on normotensive patients.^a

Major Toxicities

Intracavernosal Therapy

Intracavernosal therapy for impotence could result in persistent priapism (a medical emergency) which requires immediate medical and/or surgical intervention.¹⁰³ ¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ ¹¹⁰ ¹¹³ ¹¹⁵ ¹¹⁶ ¹²⁰ ¹²⁴ ¹²⁵ ¹²⁶ ¹²⁷ ¹²⁸ If not treated immediately, penile tissue damage and permanent loss of potency may occur.¹⁴² ¹⁵² ¹⁶¹ ¹⁶² ¹⁶³

Intracavernosal therapy (administered by self-injection) may be problematic in patients receiving anticoagulants, those who cannot tolerate transient hypotension, and those with poor manual dexterity, poor vision, or severe psychiatric disease.¹²⁵

General Precautions

GI Conditions

Use with caution in patients with gastritis or peptic ulcer.^a

MI

Monitor left ventricular function and ECG continuously during IV infusion of the drug.^a

Specific Populations

Pregnancy

Category C.¹⁷⁷

Lactation

Not known whether phentolamine is distributed into milk.¹⁷⁷ Discontinue nursing or the drug.¹⁷⁷

Common Adverse Effects

Abdominal pain, nausea, vomiting, diarrhea, exacerbation of peptic ulcer, weakness, dizziness, flushing, orthostatic hypotension, and nasal congestion.¹⁷⁷ ^a

Interactions for Phentolamine Mesylate

Specific Drugs

Drug	Interaction	Comments
Antihypertensive Agents	Possible false-positive test for pheochromocytoma^a	Withdraw antihypertensive agents and do not perform phentolamine test until blood pressure returns to pretreatment hypertensive levels^a
Epinephrine	Possible paradoxical fall in blood pressure^a	Do not administer for phentolamine-associated hypotension^a
Opiate analgesics	Possible false-positive test for pheochromocytoma^a	Withdraw opiates ≥24 hours (preferably 48–72 hours) prior to phentolamine test^a
Rauwolfia alkaloids	Possible false-positive test for pheochromocytoma^a	Withdraw rauwolfia drugs at least 4 weeks prior to phentolamine test^a
Sedatives	Possible false-positive test for pheochromocytoma^a	Withdraw sedatives ≥24 hours (preferably 48–72 hours) prior to phentolamine test.^a

Phentolamine Mesylate Pharmacokinetics

Absorption

Onset

IV injection: maximum effect (in positive pheochromocytoma test) within 2 minutes.¹⁷⁷ ^a

IM injection: maximum effect usually within 20 minutes.¹⁷⁷ ^a

Intracavernous injection: (penile erection) within 10 minutes.¹⁰⁵ ¹⁰⁶ ¹⁰⁸ ¹¹³ ¹¹⁴ ¹¹⁶ ¹¹⁸ ¹¹⁹ ¹²⁴

Duration

IV injection: return to pretest BP usually within 15–30 minutes or less.^a

IM injection: return to pretest BP within 3–4 hours.^a

Intracavernous injection: penile erection may persist for 1 to several hours.¹⁰⁵ ¹⁰⁶ ¹⁰⁸ ¹¹³ ¹¹⁴ ¹¹⁶ ¹¹⁸ ¹¹⁹ ¹²⁴

Distribution

Extent

Not known whether phentolamine is distributed into milk.¹⁷⁷ ^a

Elimination

Elimination Route

Excreted in urine (10–13%) as unchanged drug; the fate of the remainder is not known.¹⁷⁷ ^a

Half-life

19 minutes following IV administration.¹⁷⁷

Stability

Storage

Parenteral

Powder for Injection

15–30°C.¹⁷⁷ ^a

Use reconstituted solution at time of preparation; do not store.¹⁷⁷ ^a

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Drug Compatibility

Admixture CompatibilityHID
Compatible
Dobutamine HCl
Verapamil HCl

Y-Site CompatibilityHID
Compatible
Amiodarone HCl

ActionsActions

Competitively blocks α-adrenergic receptors (primarily excitatory responses of smooth muscle and exocrine glands), but action is transient and incomplete.^a

More effective in antagonizing responses to circulating epinephrine and/or norepinephrine than in antagonizing responses to mediator released at the adrenergic nerve ending.^a

Causes peripheral vasodilation and decreases peripheral resistance, primarily by direct relaxation of vascular smooth muscle, but α-adrenergic blockade also contributes to vasodilation.^a

Stimulates β-adrenergic receptors and produces a positive inotropic and chronotropic effect on the cardiac muscle (increasing cardiac output)^a and vascular effects on vascular smooth muscle.¹⁷⁷

Usual doses lower BP maintained by circulating epinephrine or norepinephrine, but have little effect on the BP of healthy individuals or patients with essential hypertension.^a

In patients with AMI associated with hypertension and/or left ventricular failure, administration of IV phentolamine results in improvement in left ventricular performance; cardiac output, stroke index, heart rate, and cardiac index are increased and left ventricular filling pressure is decreased.^a

Advice to Patients

Advise patients (using intracavernosal therapy for impotence) to contact their clinician if they develop a persistent (e.g., longer than 4 hours) erection during such therapy.¹³² ¹³³

Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.¹⁷⁷ ^a

Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Phentolamine Mesylate
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection	5 mg*	Phentolamine Mesylate for Injection

Disclaimer

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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