Anafranil

Anafranil is a brand name of clomipramine, approved by the FDA in the following formulation(s):

ANAFRANIL (clomipramine hydrochloride - capsule; oral)

• 
  Manufacturer: MALLINCKRODT LLC
  
  Approval date: December 29, 1989
  
  Strength(s): 25MG ^[AB], 50MG ^[RLD][AB], 75MG ^[AB]

Has a generic version of Anafranil been approved?

Yes. The following products are equivalent to Anafranil:

clomipramine hydrochloride capsule; oral

• 
  Manufacturer: MYLAN
  
  Approval date: April 30, 1998
  
  Strength(s): 25MG ^[AB], 50MG ^[AB], 75MG ^[AB]


• 
  Manufacturer: SANDOZ
  
  Approval date: March 29, 1996
  
  Strength(s): 25MG ^[AB], 50MG ^[AB], 75MG ^[AB]


• 
  Manufacturer: TARO
  
  Approval date: December 31, 1996
  
  Strength(s): 25MG ^[AB], 50MG ^[AB], 75MG ^[AB]


• 
  Manufacturer: TEVA
  
  Approval date: August 26, 1997
  
  Strength(s): 25MG ^[AB], 50MG ^[AB], 75MG ^[AB]

Note: Fraudulent online pharmacies may attempt to sell an illegal generic version of Anafranil. These medications may be counterfeit and potentially unsafe. If you purchase medications online, be sure you are buying from a reputable and valid online pharmacy. Ask your health care provider for advice if you are unsure about the online purchase of any medication.

See also: About generic drugs.

Related Patents

There are no current U.S. patents associated with Anafranil.

See also...

• Anafranil Consumer Information (Wolters Kluwer)
• Anafranil Consumer Information (Cerner Multum)
• Anafranil Advanced Consumer Information (Micromedex)
• Anafranil AHFS DI Monographs (ASHP)
• Clomipramine Consumer Information (Wolters Kluwer)
• Clomipramine Consumer Information (Cerner Multum)
• Clomipramine Advanced Consumer Information (Micromedex)
• Clomipramine Hydrochloride AHFS DI Monographs (ASHP)

Celecoxib Genfar

Celecoxib Genfar may be available in the countries listed below.

Ingredient matches for Celecoxib Genfar

Celecoxib

Celecoxib is reported as an ingredient of Celecoxib Genfar in the following countries:

• Colombia


• Ecuador

International Drug Name Search

Eramux

Eramux may be available in the countries listed below.

Ingredient matches for Eramux

Eprazinone

Eprazinone dihydrochloride (a derivative of Eprazinone) is reported as an ingredient of Eramux in the following countries:

• Vietnam

International Drug Name Search

Angiomax

Generic Name: Bivalirudin
Class: Direct Thrombin Inhibitors
Chemical Name: d - Phenylalanyl - l - prolyl - l - arginyl - l - prolylglycylglycylglycylglycyl - l - asparaginylglycyl - l - α - aspartyl - l - phenylalanyl - l - α - glutamyl - l - α - glutamyl - l - isoleucyl - l - prolyl - l - α - glutamyl - l - α - glutamyl - l - tyrosyl - l - leucine
CAS Number: 128270-60-0

Special Alerts:

The Editors of AHFS Drug Information (AHFS DI) and AHFS DI Essentials wish to inform you of an error in the monographs for bivalirudin 20:12.04.12 that resulted from an error in one of the cited references, the American College of Chest Physicians (ACCP) guideline on treatment and prevention of heparin-induced thrombocytopenia (Warkentin TE, Greinacher A, Koster A et al. Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians evidence-based clinical practice guidelines (8th ed). Chest. 2008; 133 (Suppl):340S-80S).^{10 25}

The error appears under the subhead Heparin-induced Thrombocytopenia in Patients Undergoing Cardiac Surgery, in Dosage and Administration. In the second sentence under this subhead, the statement should read:

“During cardiopulmonary bypass, initially, 1 mg/kg by direct IV injection followed by 2.5 mg/kg per hour by continuous IV infusion has been used;^{10 24} if needed, additional direct IV doses of 0.1–0.5 mg/kg have been given to maintain a 2.5-fold or greater prolongation of the baseline ACT.²⁴ ”

The originally stated dosage of 0.1–0.5 mg for additional direct IV doses of bivalirudin is incorrect.²⁵

The following reflects the corrected version of this information, incorporating the change noted above.

Introduction

Anticoagulant; synthetic peptide analog of hirudin, an anticoagulant polypeptide found in the saliva of the medicinal leech (Hirudo medicinalis).^{1 2 3 4 5 6}

Uses for Angiomax

Acute Ischemic Complications of Percutaneous Coronary Intervention

Used with aspirin to reduce the risk of acute ischemic complications (e.g., death, MI, need for urgent revascularization procedures) in patients with unstable angina or non-ST-segment-elevation MI (i.e., non-ST-segment-elevation acute coronary syndromes) undergoing PCI, including percutaneous transluminal coronary angioplasty (PTCA).^{1 8 9 11 15 17}

American College of Chest Physicians (ACCP) recommends anticoagulant therapy (e.g., heparin, low molecular weight heparin, bivalirudin, fondaparinux) for all patients presenting with non-ST-segment-elevation acute coronary syndromes.¹⁷ ACCP suggests the use of bivalirudin in combination with clopidogrel over heparin for initial antithrombotic therapy in patients at moderate to high risk for an ischemic event and who are scheduled for very early coronary angiography (within <6 hours).¹⁷

Efficacy in patients with non-ST-segment-elevation acute coronary syndromes undergoing PCI similar to that of high-dose heparin.^{1 5}

Used with aspirin and “provisional” treatment with a GP IIb/IIIa-receptor inhibitor in selected patients undergoing PCI who have complications (i.e., prolonged ischemia, decreased perfusion [TIMI grade 0–2 flow] or slow reflow, dissection with decreased perfusion, new or suspected thrombus, persistent residual stenosis, distal embolism, unplanned or suboptimal stenting, side branch closure, abrupt closure, or other clinical instability).^{1 8 11 14 17} Efficacy in such patients similar to that of heparin and routine treatment with a GP IIb/IIIa-receptor inhibitor.^{1 8 9 11 14 16 17}

ACC, AHA, and the Society for Cardiovascular Angiography and Interventions (SCAI) suggest bivalirudin as an alternative to heparin and a GP IIb/IIIa-receptor inhibitor in patients undergoing PCI who are at low risk for ischemic complications.¹⁵

ACCP recommends either bivalirudin and provisional treatment with a GP IIb/IIIa-receptor inhibitor or heparin and routine treatment with a GP IIb/IIIa-receptor inhibitor in patients with non-ST-segment-elevation acute coronary syndromes undergoing PCI who are at low to moderate risk for ischemic complications.¹⁷

Safety and efficacy not established in patients with acute coronary syndromes who are not undergoing PTCA or PCI.¹

Heparin-induced Thrombocytopenia in Patients Undergoing PCI

Used with aspirin in patients undergoing PCI who have, or are at risk for, heparin-induced thrombocytopenia (HIT).^{1 10 15}

ACC/AHA/SCAI recommend bivalirudin or argatroban and ACCP recommends bivalirudin, argatroban, or lepirudin as a substitute for unfractionated heparin or low molecular weight heparin in patients with HIT undergoing PCI.^{10 15}

ACCP suggests use of a nonheparin anticoagulant over continued therapy with unfractionated or low molecular weight heparin in patients with a history of HIT (antibody negative) who require cardiac catheterization or PCI.¹⁰

Heparin-induced Thrombocytopenia in Patients Undergoing Cardiac Surgery

Recommended as a substitute for heparin in patients with acute HIT (thrombocytopenic and HIT-antibody positive) who require cardiac surgery† (e.g., coronary artery bypass grafting [CABG]).^{10 24} ACCP recommends delaying surgery (if possible) until HIT antibodies are no longer detected or use of bivalirudin for intraoperative anticoagulation during cardiopulmonary bypass or “off-pump” cardiac surgery, provided special precautions to prevent blood stasis are followed.^{10 24 26} (See Patients with HIT Undergoing Cardiac Surgery under Cautions.)

Acute ST-Segment-Elevation MI

Used as an alternative to heparin in patients with acute ST-segment-elevation MI†.^{20 21 22} May be used in patients who have been pretreated with heparin and who are to undergo PCI; may also be used as an alternative to heparin in patients who have received fondaparinux in conjunction with a thrombolytic agent prior to PCI.²⁰

Angiomax Dosage and Administration

General

• 
  

  Manufacturer states that bivalirudin is intended for use concomitantly with aspirin 300–325 mg daily.¹ However, ACC/AHA/SCAI and ACCP recommend lower maintenance dosages of aspirin (e.g., 75–162 mg daily).^{15 17 18 19 20 21 23}

  
  

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by direct IV injection followed by IV infusion.¹ Do not administer IM.¹

Reconstitution

Reconstitute vial containing 250 mg of lyophilized bivalirudin with 5 mL of sterile water for injection (swirl gently) to provide a solution containing 50 mg/mL.¹

Discard any unused reconstituted solution.¹

Dilution

Dilute reconstituted solution in 50 mL of 5% dextrose or 0.9% sodium chloride injection to a final concentration of 5 mg/mL for direct IV injection and infusion.¹

For low-rate infusion, further dilute the 5-mg/mL solution in 500 mL of 5% dextrose or 0.9% sodium chloride injection to a final concentration of 0.5 mg/mL.^{1 7}

Dosage

Adults

Acute Ischemic Complications of PCI

IV

0.75 mg/kg (5-mg/mL solution) by direct IV injection immediately before PCI, followed by 1.75 mg/kg per hour (5-mg/mL solution) by continuous IV infusion for the duration of the procedure.¹ Obtain an activated clotting time (ACT) (as measured by a Hemochron device) 5 minutes after initial loading dose and administer an additional direct IV dose of 0.3 mg/kg if needed (e.g., if the ACT is <225 seconds).^{1 8}

May continue infusion for up to 4 hours after the procedure if necessary.¹ If needed, administer an additional IV infusion (0.5-mg/mL solution) at 0.2 mg/kg per hour for up to 20 hours.¹

Heparin-induced Thrombocytopenia in Patients Undergoing PCI

IV

0.75 mg/kg (5-mg/mL solution) by direct IV injection immediately before PCI, followed by 1.75 mg/kg per hour (5-mg/mL solution) by continuous IV infusion for the duration of the procedure.¹

May continue infusion for up to 4 hours after the procedure if necessary.¹ If needed, administer an additional IV infusion (0.5-mg/mL solution) at 0.2 mg/kg per hour for up to 20 hours.¹

Heparin-induced Thrombocytopenia in Patients Undergoing Cardiac Surgery†

IV

During “off-pump” cardiac surgery (i.e., without cardiopulmonary bypass), 0.75 mg/kg by direct IV injection, followed by 1.75 mg/kg per hour by continuous IV infusion to maintain an ACT >300 seconds has been used.^{10 26}

During cardiopulmonary bypass, initially, 1 mg/kg by direct IV injection followed by 2.5 mg/kg per hour by continuous IV infusion has been used;^{10 24} if needed, additional direct IV doses of 0.1–0.5 mg/kg have been given to maintain a 2.5-fold or greater prolongation of the baseline ACT.²⁴ In addition, 50 mg of bivalirudin is added to the recirculating priming fluid of the cardiopulmonary bypass circuit.^{10 24}

Acute ST-Segment-Elevation MI†

IV

0.25 mg/kg by direct IV injection followed by 0.5 mg/kg per hour by continuous IV infusion for the first 12 hours, then 0.25 mg/kg per hour for the subsequent 36 hours, has been used.^{21 22} Obtain aPTT 12 and 24 hours after the initial dosage; adjust dosage if needed.²¹

Special Populations

Renal Impairment

Reduction of the initial loading dose not necessary in patients with moderate to severe renal impairment.^{1 7} Closely monitor activated clotting time (ACT) in patients with renal impairment.¹ Reduce infusion rate to 1 mg/kg per hour in patients with severe renal impairment (Cl_cr <30 mL/minute).¹ In dialysis-dependent patients, reduce off-dialysis infusion rate to 0.25 mg/kg per hour.¹

Cautions for Angiomax

Contraindications

• 
  

  Active major bleeding.¹

  
  


• 
  

  Known hypersensitivity to bivalirudin or any ingredient in the formulation.¹

  
  

Warnings/Precautions

Warnings

Hematologic Effects

Possible bleeding, especially at site of arterial puncture.^{1 7} Unexplained decreases in hematocrit, hemoglobin, or BP may indicate hemorrhage.¹

Discontinue if severe hemorrhage occurs.¹ Use with caution in patients with an increased risk of hemorrhage.^{1 7}

Increased risk of potentially fatal thrombosis during vascular brachytherapy procedures; use caution.¹ Assess catheter function frequently by attempting to aspirate blood, and ensure patency by repeated flushing.¹ Minimize conditions promoting stasis within the catheter or circulatory system.^{1 10}

Sensitivity Reactions

Hypersensitivity

Positive bivalirudin antibody tests found rarely in clinical studies; however, no allergic or anaphylactic reactions reported.^{1 7}

General Precautions

Factors Increasing Risk of Hemorrhage

Increased risk of major bleeding events with concomitant heparin, warfarin, thrombolytic, or GP IIb/IIIa-receptor inhibitor therapy in clinical trials.¹ (See Common Adverse Effects and see Specific Drugs under Interactions.) No experience with concomitant administration of plasma expanders such as dextran.¹

Use with caution in patients with disease states associated with increased risk of hemorrhage.¹

Brachytherapy Procedures

Use with caution during vascular brachytherapy procedures because of an increased risk of potentially fatal thrombosis.¹

Patients with HIT Undergoing Cardiac Surgery

Possible formation of clots due to degradation of bivalirudin in areas of blood stasis; special maneuvers needed to avoid stasis within the cardiopulmonary bypass circuit during and after cardiac surgery.^{10 24 26} Avoid use of cardiotomy suction; also avoid use of patient blood to test graft patency or for cardioplegia solutions.^{10 24 26}

Specific Populations

Pregnancy

Category B.¹

Lactation

Not known whether bivalirudin is distributed into milk.¹ Use with caution.¹

Pediatric Use

Safety and efficacy not established in pediatric patients.¹

Geriatric Use

No substantial differences in safety or efficacy relative to younger adults.^{1 7}

Renal Impairment

Dosage reduction recommended in patients with moderate to severe renal impairment.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Major hemorrhagic events less frequent with bivalirudin with or without provisional GP IIb/IIIa-receptor inhibitor therapy (2.3%) compared with unfractionated heparin and routine GP IIb/IIIa-receptor inhibitor therapy (4%).¹

Nonhemorrhagic effects in patients with unstable angina undergoing PTCA: Back pain,¹ pain (unspecified),¹ nausea,¹ headache,¹ hypotension,¹ injection site pain,¹ insomnia,¹ hypertension,¹ vomiting,¹ pelvic pain,¹ anxiety,¹ bradycardia,¹ dyspepsia,¹ abdominal pain,¹ fever,¹ nervousness,¹ urinary retention.¹

Nonhemorrhagic effects in patients undergoing PCI and receiving provisional therapy with a GP IIb/IIIa-receptor inhibitor: Back pain, angina pectoris,¹ pain (unspecified),¹ hypotension,¹ nausea,¹ injection site pain,¹ headache,¹ chest pain.¹

Interactions for Angiomax

Specific Drugs

Drug	Interaction	Comments
Aspirin	Increased risk of hemorrhage13
GP IIb/IIIa-receptor inhibitors	Increased risk of hemorrhage1
Heparin	Increased risk of hemorrhage1
Heparin, low molecular weight	No apparent pharmacodynamic interaction13	Limited data; safety and efficacy of combination therapy not established13
Plasma-volume expanders (e.g., dextran)	No experience with concomitant therapy1
Thrombolytic agents	Increased risk of hemorrhage1
Ticlopidine	No apparent pharmacodynamic interaction13	Limited data; safety and efficacy of combination therapy not established13
Warfarin	Increased risk of hemorrhage1

Angiomax Pharmacokinetics

Absorption

Onset

Immediate anticoagulant effect.¹

Duration

Effects are dose- and concentration-dependent and reversible; thrombin slowly cleaves the bivalirudin-Arg₃-Pro₄ bond, which results in recovery of the thrombin active site function.^{1 3 4} Coagulation times return to normal approximately 1–2 hours after cessation of infusion.^{1 7}

Distribution

Extent

Not known whether the drug is distributed into human milk.¹

Plasma Protein Binding

Does not bind to plasma proteins (other than thrombin).¹

Elimination

Metabolism

Cleared from the plasma by a combination of renal mechanisms and intracellular proteolysis.^{1 b}

Elimination Route

Approximately 20% of unchanged bivalirudin is cleared renally, and the remainder presumably undergoes intracellular proteolysis.^b

Half-life

22 minutes.¹

Special Populations

In patients with mild renal impairment (GFR of 60–89 mL/minute), half-life is 25 minutes.¹

In patients with moderate renal impairment (GFR of 30–59 mL/minute), half-life is 34 minutes.¹

In patients with severe renal impairment (GFR of 10–29 mL/minute), half-life is 57 minutes.¹

In dialysis-dependent patients, off-dialysis half-life is 3.5 hours.¹

Total body clearance reduced by about 20% in patients with moderate to severe renal impairment and by 80% in dialysis-dependent patients.¹

Approximately 25% of drug removed by hemodialysis.¹

Stability

Storage

Parenteral

Powder for Injection

20–25°C (may be exposed to 15–30°C).¹

Reconstituted solution (50 mg/mL) may be stored at 2–8°C for up to 24 hours.¹

Diluted IV solutions (0.5–5 mg/mL) are stable at room temperature for up to 24 hours.¹

Compatibility

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

Parenteral

Solution Compatibility¹

Compatible
Dextrose 5% in water
Sodium chloride 0.9%

Drug Compatibility^HID

Y-Site CompatibilityHID

Compatible
Abciximab
Alfentanil HCl
Amikacin sulfate
Aminophylline
Ampicillin sodium
Ampicillin sodium-sulbactam sodium
Azithromycin
Aztreonam
Bretylium tosylate
Bumetanide
Butorphanol tartrate
Calcium gluconate
Cefazolin sodium
Cefepime HCl
Cefotaxime sodium
Cefoxitin sodium
Ceftazidime
Ceftizoxime sodium
Ceftriaxone sodium
Cefuroxime sodium
Cimetidine HCl
Ciprofloxacin
Clindamycin phosphate
Co-trimoxazole
Dexamethasone sodium phosphate
Digoxin
Diltiazem HCl
Diphenhydramine HCl
Dobutamine HCl
Dopamine HCl
Doxycycline hyclate
Droperidol
Enalaprilat
Ephedrine sulfate
Epinephrine HCl
Epoprostenol sodium
Eptifibatide
Erythromycin lactobionate
Esmolol HCl
Famotidine
Fentanyl citrate
Fluconazole
Furosemide
Gentamicin sulfate
Haloperidol lactate
Heparin sodium
Hydrocortisone sodium succinate
Hydromorphone HCl
Isoproterenol HCl
Labetalol HCl
Levofloxacin
Lidocaine HCl
Lorazepam
Magnesium sulfate
Mannitol
Meperidine HCl
Methylprednisolone sodium succinate
Metoclopramide HCl
Metronidazole
Midazolam HCl
Milrinone lactate
Morphine sulfate
Nalbuphine HCl
Nitroglycerin
Norepinephrine bitartrate
Phenylephrine HCl
Piperacillin sodium-tazobactam
Potassium chloride
Procainamide HCl
Promethazine HCL
Ranitidine HCl
Sodium bicarbonate
Sodium nitroprusside
Sufentanil citrate
Theophylline
Thiopental sodium
Ticarcillin disodium-clavulanate potassium
Tirofiban HCl
Tobramycin sulfate
Verapamil HCl
Warfarin sodium
Incompatible
Alteplase
Amiodarone HCl
Amphotericin B
Chlorpromazine HCl
Diazepam
Prochlorperazine edisylate
Reteplase
Vancomycin HCl

ActionsActions

• 
  

  Specific and reversible direct thrombin inhibitor that binds to circulating and clot-bound thrombin.^{1 2 3 4}

  
  


• 
  

  Inhibition of thrombin prevents various steps in the coagulation process (e.g., activation of factors V, VIII, and XIII; conversion of fibrinogen to fibrin; platelet activation and aggregation).^{1 2 3 4}

  
  


• 
  

  Prolongs activated clotting time (ACT), aPTT, thrombin time (TT), and PT.^{1 7}

  
  

Advice to Patients

• 
  

  Importance of patients reporting any signs of bleeding (e.g., bruising, petechiae, hematuria) to clinicians immediately.¹

  
  


• 
  

  Importance of patients informing clinicians of history of bleeding disorders or impaired renal function.¹

  
  


• 
  

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

  
  


• 
  

  Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant diseases.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.

Bivalirudin

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection, for IV infusion	250 mg	Angiomax	Medicines Company

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 March 25, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

1. The Medicines Company. Angiomax (bivalirudin) for injection prescribing information. Cambridge, MA; 2005 Dec 6.

2. Haines ST, Bussey HI. Thrombosis and the pharmacology of antithrombotic agents. Ann Pharmacother. 1995; 29:892-905. [IDIS 353388] [PubMed 8547739]

3. Stringer KA, Lindenfeld J. Hirudins: antithrombin anticoagulants. Ann Pharmacother. 1992; 26:1535-40. [IDIS 306624] [PubMed 1482812]

4. Bates SM, Weitz JI. Direct thrombin inhibitors for treatment of arterial thrombosis: potential differences between bivalirudin and hirudin. Am J Cardiol. 1998; 82:12-8P.

5. Bittl JA, Strony J, Brinker JA et al for the Hirulog Angioplasty Study investigators. Treatment with bivalirudin (hirulog) as compared with heparin during coronary angioplasty for unstable or postinfarction angina. N Engl J Med. 1995; 333:764-9. [IDIS 353197] [PubMed 7643883]

6. Bittl JA, Feit F for Hirulog Angioplasty Study investigators. A randomized comparison of bivalirudin and heparin in patients undergoing coronary angioplasty for postinfarction angina. Am J Cardiol. 1998; 82:43-9P. [PubMed 9671007]

7. The Medicines Company, Cambridge, MA: Personal communication.

8. Lincoff AM, Bittl JA, Harrington RA et al. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA. 2003; 289:853-63. [IDIS 493155] [PubMed 12588269]

9. Saw J, Lincoff M, DeSmet W et al. Lack of clopidogrel pretreatment effect on the relative efficacy of bivalirudin with provisional glycoprotein IIb/IIIa blockade compared to heparin with routine glycoprotein IIb/IIIa blockade: a REPLACE-2 substudy. J Am Coll Cardiol. 2004; 44:1194-9. [IDIS 524399] [PubMed 15364319]

10. Warkentin TE, Greinacher A, Koster A et al. Treatment and prevention of heparin-induced thrombocytopenia: American College of Chest Physicians evidenced-based clinical practice guidelines (8th ed) Chest. 2008; 133 (Suppl):340S-80S

11. Popma JJ, Berger P, Ohman EM et al. Antithrombotic therapy in patients undergoing percutaneous coronary intervention. Chest. 2001; 119(Suppl):321S-36S.

12. Harrington RA, Becker RC, Ezekowitz M et al. Antithrombotic therapy in coronary artery disease. Chest. 2004; 126:513S-48S. [IDIS 523845] [PubMed 15383483]

13. The Medicines Company. Angiomax (bivalirudin) for injection prescribing information. Cambridge, MA; 2002 Jun 18.

14. Lincoff, AM, Kleiman NS, Kereiakes DJ et al. Long-term efficacy of bivalirudin and provisional glycoprotein IIb/IIIa blockade vs heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary revascularization: REPLACE-2 randomized trial. JAMA. 2004; 292:696-703.

15. Smith SC, Feldman TE, Hirschfeld JW et al. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/SCAI Writing Committee to Revise the 2001 Guidelines for Percutaneous Coronary Intervention). 2005. Available at the American College of Cardiology web site.

16. Lansky AJ, Hochman JS, Ward PA et al. Percutaneous coronary intervention and adjunctive pharmacotherapy in women: a statement for healthcare professionals from the American Heart Association. Circulation. 2005; 111:940-5. [PubMed 15687113]

17. Harrington RA, Becker RC, Cannon CP et al. Antithrombotic therapy for non-ST-segment elevation acute coronary syndromes.American College of Chest Physicians evidenced-based clinical practice guidelines (8th ed). Chest. 2008; 133:670S-707S. [PubMed 18574276]

18. King SB, Smith SC, Hirshfeld JW et al. 2007 focused update of the ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2008; 51:172-9. [PubMed 18191745]

19. Becker RC, Meade TW, Berger PB et al. The primary and secondary prevention of coronary artery disease: American College of Chest Physicians evidenced-based clinical practice guidelines (8th ed). Chest. 2008; 133 (Suppl): 776S-814S. [PubMed 18574278]

20. Antman EM, Hand M, Armstrong PW et al. 2007 focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction. J Am Coll Cardiol. 2008; 51:210-47. [PubMed 18191746]

21. Goodman SG, Menon V, Cannon CP et al. Acute ST-segment elevation myocardial infarction: American College of Chest Physicians evidenced-based clinical practice guidelines (8th ed). Chest. 2008; 133 (Suppl):708S-75S. [PubMed 18574277]

22. Schulman S, Beyth RJ, Kearon C et al. Hemorrhagic complications of anticoagulant and thrombolytic treatment: American College of Chest Physicians evidenced-based clinical practice guidelines (8th ed). Chest. 2008; 133 (Suppl):257S-98S. [PubMed 18574268]

23. Anderson JL, Adams CD, Antman EM et al. ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction). Available at ACC website. Accessed 2008 Oct 15.

24. Koster A, Dyke CM, Aldea G et al. Bivalirudin during cardiopulmonary bypass in patients with previous or acute heparin-induced thrombocytopenia and heparin antibodies: results of the CHOOSE-ON trial. Ann Thorac Surg. 2007; 83:572-7.

25. Lewis SZ (American College of Chest Physicians, Northbrook, IL): Personal communication. 2011 Mar 15.

26. Dyke CM, Aldea G, Koster A et al. Off-pump coronary artery bypass with bivalirudin for patients with heparin-induced thrombocytopenia or antiplatelet factor four/heparin antibodies. Ann Thorac Surg. 2007; 84:836-40.

b. Robson R, White H, Aylward P et al. Bivalirudin pharmacokinetics and pharmacodynamics: effect of renal function, dose, and gender. Clin Pharmacol Ther. 2002; 71:433-39. [PubMed 12087346]

HID. Trissel LA. Handbook on injectable drugs. 14th ed; Bethesda, MD: American Society of Health-System Pharmacists; 2007:207-13.

More Angiomax resources

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

• Angiomax Prescribing Information (FDA)


• Angiomax MedFacts Consumer Leaflet (Wolters Kluwer)


• Angiomax Concise Consumer Information (Cerner Multum)


• Angiomax Advanced Consumer (Micromedex) - Includes Dosage Information


• Bivalirudin Professional Patient Advice (Wolters Kluwer)

Compare Angiomax with other medications

• Angina
• Percutaneous Coronary Intervention

alemtuzumab

Generic Name: alemtuzumab (AL em TOOZ oo mab)

Brand Names: Campath

What is alemtuzumab?

Alemtuzumab is an antibody made from animal DNA.

Alemtuzumab is used to treat chronic lymphocytic leukemia.

Alemtuzumab is usually given after other medications have been tried without successful treatment.

Alemtuzumab may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about alemtuzumab?

You should not receive this medication if you are allergic to alemtuzumab, or if you have HIV or AIDS, any type of active infection, or if you are allergic to mouse or hamster proteins.

Before receiving alemtuzumab, tell your doctor if you have heart disease, a bleeding or blood clotting disorder, diabetes, a stomach or intestinal disorder, or asthma or other breathing problem.

Tell your doctor if you are pregnant or plan to become pregnant during treatment.

If a man fathers a child while using this medication, the baby may have birth defects. Use a condom to prevent pregnancy during your treatment. Continue using condoms for at least 6 months after you stop using alemtuzumab.

Do not breast-feed a baby while you are receiving alemtuzumab and for at least 3 months after your treatment ends.

You may be given other medications together with alemtuzumab to help prevent infection or certain side effects.

Alemtuzumab can lower the blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. To be sure your blood cells do not get too low, your blood will need to be tested on a regular basis. Do not miss any scheduled visits to your doctor.

Avoid being near people who have colds, the flu, or other contagious illnesses. Contact your doctor at once if you develop signs of infection.

Do not receive a "live" vaccine while you are being treated with alemtuzumab, and for at least several weeks after your treatment ends. The live vaccine may not work as well during this time, and may not fully protect you from disease.

What should I discuss with my health care provider before taking alemtuzumab?

You should not receive this medication if you are allergic to alemtuzumab, or if you have:

• 
  

  HIV or AIDS;

  
  


• 
  

  any type of active infection; or

  
  


• 
  

  if you are allergic to mouse or hamster proteins.

  
  

Before receiving alemtuzumab, tell your doctor if you are allergic to any drugs, or if you have:

• 
  

  heart disease;

  
  


• 
  

  a bleeding or blood clotting disorder;

  
  


• 
  

  diabetes;

  
  


• 
  

  a stomach or intestinal disorder; or

  
  


• 
  

  asthma or other breathing disorder.

  
  

If you have any of these conditions, you may not be able to use alemtuzumab, or you may need dosage adjustments or special tests during treatment.

FDA pregnancy category C. This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

If a man fathers a child while using this medication, the baby may have birth defects. Use a condom to prevent pregnancy during your treatment. Continue using condoms for at least 6 months after you stop using alemtuzumab.

It is not known whether alemtuzumab passes into breast milk or if it could harm a nursing baby. Do not breast-feed a baby while you are receiving alemtuzumab and for at least 3 months after your treatment ends.

How is alemtuzumab given?

Alemtuzumab is given as an injection through a needle placed into a vein. You will receive this injection in a clinic or hospital setting. The medicine must be given slowly through an IV infusion, and can take up to 2 hours to complete.

Alemtuzumab is given as an injection through a needle placed into a vein. Your doctor, nurse, or other healthcare provider will give you this injection. You may be given instructions on how to inject your medicine at home. Do not use this medicine at home if you do not fully understand how to give the injection and properly dispose of needles and other items used in giving the medicine.

Use each needle and syringe only one time. Throw away used needles and syringes in a puncture-proof container. If your medicine does not come with such a container, ask your pharmacist where you can get one. Keep this container out of the reach of children and pets. Your pharmacist can tell you how to properly dispose of the container.

Do not shake the medication vial (bottle). Vigorous shaking can ruin the medicine. Do not mix your alemtuzumab dose until you are ready to give yourself an injection. Do not use the medication if it has changed colors or has any particles in it. Call your doctor for a new prescription.

You may be given other medications together with alemtuzumab to help prevent certain side effects.

You may also need to take an antibiotic to prevent infections while you are receiving alemtuzumab. Take the antibiotic for the entire length of time prescribed by your doctor.

Alemtuzumab can lower the blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. To be sure your blood cells do not get too low, your blood will need to be tested on a regular basis. Do not miss any scheduled visits to your doctor.

Tell your doctor if you have stopped using alemtuzumab for longer than 7 days for any reason. You may need to restart the medication at a lower dose.

If you keep this medicine at home, store it in a refrigerator, and protect it from light. Do not allow the medicine to freeze. If it does freeze, thaw in a refrigerator. Do not warm the medication.

What happens if I miss a dose?

Call your doctor for instructions if you miss a dose of this medication.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include feeling short of breath, or urinating less than usual or not at all.

What should I avoid while taking alemtuzumab?

Avoid being near people who have colds, the flu, or other contagious illnesses. Contact your doctor at once if you develop signs of infection.

Do not receive a "live" vaccine while you are being treated with alemtuzumab, and for at least several weeks after your treatment ends. The live vaccine may not work as well during this time, and may not fully protect you from disease.

Alemtuzumab side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Some people receiving a alemtuzumab injection have had a reaction to the infusion (when the medicine is injected into the vein). Tell your caregiver right away if you feel dizzy, hot or cold, nauseated, light-headed, sweaty, itchy, or have a fast heartbeat, chest tightness, or trouble breathing during the injection. Call your doctor at once if you have any of these serious side effects:

• 
  

  pale skin, easy bruising or bleeding, unusual weakness;

  
  


• 
  

  chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;

  
  


• 
  

  fever, chills, body aches, flu symptoms;

  
  


• 
  

  feeling light-headed, fainting;

  
  


• 
  

  confusion, hallucinations; or

  
  


• 
  

  white patches or sores inside your mouth or on your lips.

  
  

Less serious side effects include:

• 
  

  nausea, vomiting, stomach pain;

  
  


• 
  

  diarrhea, constipation;

  
  


• 
  

  loss of appetite;

  
  


• 
  

  headache;

  
  


• 
  

  back or chest pain;

  
  


• 
  

  sleep problems (insomnia);

  
  


• 
  

  tired feeling;

  
  


• 
  

  runny nose, sore throat; or

  
  


• 
  

  sweating, mild skin rash or itching;

  
  

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

Alemtuzumab Dosing Information

Usual Adult Dose for Chronic Lymphocytic Leukemia:

Initial dose: 3 mg daily IV over 2 hours.
Maintenance dose: Increase to 10 mg daily over 2 hours when tolerated by patient (infusion-related toxicity NCI-CTC Grade 2 or less). When 10 mg dose is tolerated, increase to maintenance level of 30 mg 3 times weekly (Monday, Wednesday, Friday) IV over 2 hours for up to 12 weeks.
Maximum dose: To decrease incidence of pancytopenia, single doses should not be greater than 30 mg and cumulative weekly doses should not be greater than 90 mg.

What other drugs will affect alemtuzumab?

There may be other drugs not listed that can affect alemtuzumab. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More alemtuzumab resources

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

• alemtuzumab Intravenous Advanced Consumer (Micromedex) - Includes Dosage Information


• Alemtuzumab Professional Patient Advice (Wolters Kluwer)


• Alemtuzumab Monograph (AHFS DI)


• Alemtuzumab MedFacts Consumer Leaflet (Wolters Kluwer)


• Campath Prescribing Information (FDA)

Compare alemtuzumab with other medications

• Chronic Lymphocytic Leukemia
• Rheumatoid Arthritis

Where can I get more information?

• Your pharmacist has information about alemtuzumab written for health professionals that you may read.

See also: alemtuzumab side effects (in more detail)

Atacand

Generic Name: Candesartan Cilexetil
Class: Angiotensin II Receptor Antagonists
VA Class: CV805
Chemical Name: (±)-1-[[Cyclohexyloxy)carbonyl]oxy]ethyl ester - 2 - ethoxy - 1 - [[2′ - (1H - tetrazol - 5 - yl)[1,1′ - biphenyl] - 4 - yl]methyl] - 1H - benzimidazole - 7 - carboxylic acid
Molecular Formula: C₃₃H_34…N₆O₆
CAS Number: 145040-37-5

• 
  

  May cause fetal and neonatal morbidity and mortality if used during pregnancy.^{1 2 4 55 56} (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

  
  


• 
  

  If pregnancy is detected, discontinue as soon as possible.^{1 2 56}

  
  

Introduction

Angiotensin II receptor (AT₁) antagonist.^{1 2 9}

Uses for Atacand

Hypertension

Management of hypertension (alone or in combination with other classes of antihypertensive agents).^{1 2 3 16 17 18 19 20 21}

One of several preferred initial therapies in hypertensive patients with chronic kidney disease, diabetes mellitus, or heart failure.⁴⁶

Can be used as monotherapy for initial management of uncomplicated hypertension; however, thiazide diuretics are preferred by JNC 7.⁴⁶

CHF

A second-line agent in the treatment of CHF; should be used only in those intolerant of ACE inhibitors.^{1 6 35 52 53}

Diabetic Nephropathy

A first-line agent in the treatment of diabetic nephropathy†.^{33 34}

Atacand Dosage and Administration

General

Hypertension

• 
  

  Fixed-combination candesartan/hydrochlorothiazide tablets should not be used for initial treatment of hypertension.^{2 5 11}

  
  

Administration

Oral Administration

Administer orally once or twice daily without regard to meals.^{1 24}

Dosage

Available as candesartan cilexetil; dosage expressed in terms of the salt.¹

Adults

Hypertension

Monotherapy

Oral

Initially, 16 mg once daily in adults without intravascular volume depletion.^{1 2 3} Adjust dosage at approximately monthly intervals (more aggressively in high-risk patients) to achieve BP control.^{4 46}

Usual dosage: 8–32 mg daily, given in 1 dose or 2 divided doses;^{1 2 5} no additional therapeutic benefit with higher dosages.^{1 2}

Combination Therapy

Oral

If BP is not adequately controlled by monotherapy with candesartan 32 mg daily, can switch to fixed-combination tablets (candesartan 32 mg and hydrochlorothiazide 12.5 mg; then candesartan 32 mg and hydrochlorothiazide 25 mg).^{2 24}

If BP is not adequately controlled by monotherapy with 25 mg of hydrochlorothiazide or if BP is controlled but hypokalemia is problematic at this dosage, can use fixed-combination tablets containing candesartan 16 mg and hydrochlorothiazide 12.5 mg.^{2 24}

CHF

Monotherapy

Oral

Initially, 4 mg once daily.¹ Increase dosage (by doubling the dosage at approximately 2-week intervals) as tolerated to a target dosage of 32 mg once daily.¹

Special Populations

Hepatic Impairment

No initial dosage adjustments necessary in patients with mild hepatic impairment.¹

Manufacturer recommends considering initial dosage reduction in patients with moderate hepatic impairment.¹

If a lower initial candesartan cilexetil dosage (<8 mg once daily) is selected in patients with moderate hepatic impairment, do not use the commercially available preparation containing candesartan cilexetil in fixed combination with hydrochlorothiazide for initial titration, because the appropriate starting dose of candesartan cilexetil is not available as a fixed-combination preparation.² Individualize and adjust dosage carefully when using the fixed combination preparation in patients with hepatic impairment .² Some clinicians recommend initial candesartan cilexetil dosage of 4 or 8 mg daily in patients with severe hepatic impairment.^{3 10 22 23 24}

Renal Impairment

Manufacturer states that no initial candesartan cilexetil dosage adjustments are necessary in patients with renal impairment.^{1 2} However, some clinicians recommend initial dosage of 4 or 8 mg daily in those with severe impairment.^{3 10 22 23 24}

Volume- and/or Salt-Depleted Patients

Correct volume and/or salt depletion prior to initiation of therapy or initiate therapy under close medical supervision using lower initial dosage.^{1 2}

Cautions for Atacand

Contraindications

• 
  

  Known hypersensitivity to candesartan or any ingredient in the formulation.^{1 2 7 24}

  
  

Warnings/Precautions

Warnings

Hypotension

Possible symptomatic hypotension, particularly in patients with intravascular volume depletion (e.g., those treated with diuretics).^{1 2} (See Volume- and/or Salt-Depleted Patients under Dosage and Administration.)

May need temporarily to reduce dosage of candesartan cilexitil and/or of a diuretic in patients with CHF; monitor BP during dosage escalation and periodically thereafter.¹ Initiate candesartan with caution in patients with CHF.¹

Transient hypotension is not a contraindication to additional doses; may reinstate therapy cautiously after BP is stabilized.^{1 2 24}

Fetal/Neonatal Morbidity and Mortality

Possible fetal and neonatal morbidity and mortality when used during pregnancy.^{1 2 56} (See Boxed Warning.) Such potential risks occur throughout pregnancy, especially during the second and third trimesters.⁵⁶

Also may increase the risk of major congenital malformations when administered during the first trimester of pregnancy.^{55 56}

Discontinue as soon as possible when pregnancy is detected, unless continued use is considered lifesaving.^{55 56} Nearly all women can be transferred successfully to alternative therapy for the remainder of their pregnancy.¹²

Malignancies

In July 2010, FDA initiated a safety review of angiotensin II receptor antagonists after a published meta-analysis found a modest but statistically significant increase in risk of new cancer occurrence in patients receiving an angiotensin II receptor antagonist compared with control.^{120 121 123 126} However, subsequent studies, including a larger meta-analysis conducted by FDA, have not shown such risk.^{126 127 128 129} Based on currently available data, FDA has concluded that angiotensin II receptor antagonists do not increase the risk of cancer.¹²⁶

Sensitivity Reactions

Anaphylactoid reactions and/or angioedema possible;^{1 2 7 13} not recommended in patients with a history of angioedema associated with or unrelated to ACE inhibitor or angiotensin II receptor antagonist therapy.^{14 21}

General Precautions

Renal Effects

Possible oliguria, progressive azotemia and, rarely, acute renal failure and/or death in patients with severe CHF.^{1 2}

Increases in BUN and S_Cr possible in patients with unilateral or bilateral renal artery stenosis.^{1 2}

Hyperkalemia

Possible hyperkalemia in patients with CHF, especially those receiving concomitant therapy with an ACE inhibitor and/or a potassium-sparing diuretic.¹ Monitor serum potassium during dosage escalation and periodically thereafter.¹

Use of Fixed Combinations

When candesartan is used in fixed combination with hydrochlorothiazide, consider the cautions, precautions, and contraindications associated with hydrochlorothiazide.²

Specific Populations

Pregnancy

Category C (1st trimester); Category D (2nd and 3rd trimesters).^{1 2} (See Boxed Warning and Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Distributed into milk in rats; not known whether distributed into human milk.^{1 2} Discontinue nursing or the drug.^{1 2}

Pediatric Use

Safety and efficacy not established in children <18 years of age.^{1 24}

Geriatric Use

No substantial differences in safety or efficacy for the treatment of hypertension relative to younger adults, but increased sensitivity cannot be ruled out.^{1 2 3}

Increased incidence of adverse effects (e.g., abnormal renal function, hypotension, hyperkalemia) and consequent discontinuance of candesartan in patients with CHF 75 years of age or older when compared with younger patients.¹

Hepatic Impairment

Systemic exposure to candesartan may be increased.¹ (See Absorption: Special Populations, under Pharmacokinetics.) Dosage adjustments may be necessary based on degree of hepatic impairment.^{1 3 10 22 23 24} (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Systemic exposure to candesartan may be increased.¹ (See Absorption: Special Populations, under Pharmacokinetics.) Some clinicians recommend initial dosage adjustment in patients with severe renal impairment.^{3 10 22 23 24} (See Renal Impairment under Dosage and Administration.)

Use of candesartan in fixed combination with hydrochlorothiazide is not recommended in patients with Cl_cr <30 mL/minute.²

Deterioration of renal function may occur in susceptible patients.^{1 30} (See Renal Effects under Cautions.)

Blacks

BP reduction may be smaller in black patients compared with nonblack patients;^{1 46} use in combination with a diuretic.⁴⁶

Common Adverse Effects

Back pain, dizziness, upper respiratory tract infection, pharyngitis, rhinitis.^{1 3}

Interactions for Atacand

Not substantially metabolized by CYP isoenzymes; has no effect on CYP isoenzymes at therapeutic concentrations.¹

Specific Drugs

Drug	Interaction	Comment
Cardiac drugs (e.g., digoxin, enalapril, hydrochlorothiazide, nifedipine)	Pharmacologic interactions unlikely1 2 3
Contraceptives, oral	Pharmacokinetic interaction unlikely1 2 3
Glyburide	Pharmacologic interaction unlikely1 2
Lithium	Increased serum lithium concentrations; possible toxicity1	Closely monitor serum lithium concentrations1
Warfarin	Pharmacologic interaction unlikely1 2 3

Atacand Pharmacokinetics

Absorption

Bioavailability

Candesartan cilexetil (prodrug) is rapidly and completely hydrolyzed to candesartan during absorption in the GI tract.^{1 2 3}

Absolute bioavailability of candesartan is about 15%.¹

Onset

Antihypertensive effect evident within 2 weeks, with maximum BP reduction after 4–6 weeks.¹

Food

Food with high-fat content does not affect bioavailability.¹

Special Populations

In patients with mild hepatic impairment (Child-Pugh class A), peak plasma concentration and AUC are increased by 56 and 30%, respectively,^{1 2} while in those with moderate hepatic insufficiency (Child-Pugh class B), peak plasma concentration and AUC are increased by 73 and 145%, respectively.^{1 2} Pharmacokinetics not studied in patients with severe hepatic impairment.^{1 2}

In patients with severe renal impairment (Cl_cr <30 mL/min/1.73 m²), AUC and peak plasma concentration after repeated dosing are approximately double the values in patients with normal renal function.¹

Distribution

Extent

Crosses the placenta and is distributed in the fetus in animals.

Crosses the blood-brain barrier poorly, if at all, in animals.¹

Distributed into milk in rats; not known whether distributed into human milk.^{1 2}

Plasma Protein Binding

>99%.¹

Elimination

Metabolism

Undergoes minor hepatic metabolism by O-deethylation to an inactive metabolite.¹

Elimination Route

Eliminated mainly as unchanged drug in urine and feces (via bile).^{1 2}

Half-life

Approximately 9 hours.¹

Special Populations

Not removed by hemodialysis.¹ Pharmacokinetics in hypertensive patients undergoing hemodialysis are similar to those in hypertensive patients with severe renal impairment.¹ (See Absorption: Special Populations, under Pharmacokinetics.)

Stability

Storage

Oral

Tablets

Tightly closed container at 25°C (may be exposed to 15–30°C).^{1 2}

Actions

• 
  

  Candesartan cilexetil (prodrug) has little pharmacologic activity until hydrolyzed to candesartan during absorption.^{1 2 3}

  
  


• 
  

  Blocks the physiologic actions of angiotensin II, including vasoconstrictor and aldosterone-secreting effects.¹

  
  


• 
  

  Does not interfere with response to bradykinins and substance P.¹

  
  

• 
  

  Does not share the ACE inhibitor common adverse effect of dry cough.^{4 5 13 24}

  
  

Advice to Patients

• 
  

  Risks of use during pregnancy.^{1 2 55 56}

  
  


• 
  

  Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.^{1 2}

  
  

• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.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.

Candesartan Cilexetil

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	4 mg	Atacand	AstraZeneca
		8 mg	Atacand	AstraZeneca
		16 mg	Atacand	AstraZeneca
		32 mg	Atacand	AstraZeneca

Candesartan Cilexetil Combinations

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	16 mg with Hydrochlorothiazide 12.5 mg	Atacand HCT	AstraZeneca
		32 mg with Hydrochlorothiazide 12.5 mg	Atacand HCT	AstraZeneca

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 01/2012. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Atacand 16MG Tablets (ASTRAZENECA LP): 30/$78.99 or 90/$219.96

Atacand 32MG Tablets (ASTRAZENECA LP): 30/$105.99 or 90/$298.97

Atacand 4MG Tablets (ASTRAZENECA LP): 30/$78.99 or 90/$216.96

Atacand 8MG Tablets (ASTRAZENECA LP): 30/$80.99 or 90/$221.98

Atacand HCT 16-12.5MG Tablets (ASTRAZENECA LP): 30/$106.99 or 90/$293.98

Atacand HCT 32-12.5MG Tablets (ASTRAZENECA LP): 30/$106.98 or 90/$294.96

Atacand HCT 32-25MG Tablets (ASTRAZENECA LP): 30/$115.99 or 90/$329.99

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, 1959-2012, Selected Revisions December 23, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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

References

Only references cited for selected revisions after 1984 are available electronically.

1. AstraZeneca. Atacand (candesartan cilexetil) tablets prescribing information. Wilmington, DE; 2005 May.

2. AstraZeneca. Atacand HCT (candesartan cilexetil-hydrochlorothiazide) tablets prescribing information. Wilmington, DE; 2005 Dec.

3. McClellan KJ, Goa KL. Candesartan cilexetil: a review of its use in essential hypertension. Drugs. 1998; 56:847-69. [PubMed 9829158]

4. National Heart, Lung, and Blood Institute National High Blood Pressure Education Program. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Bethesda, MD: National Institutes of Health; 1997 Nov. (NIH publication No. 98-4080.)

5. Anon. Drugs for hypertension. Med Lett Drugs Ther. 2001; 43:17-22. [PubMed 11242494]

6. Anon. Consensus recommendations for the management of chronic heart failure. On behalf of the membership of the advisory council to improve outcomes nationwide in heart failure. Part II. Management of heart failure. Am J Cardiol. 1999; 83:9-38A.

7. Warner KK, Visconti JA, Tschampel MM. Angiotensin II receptor blockers in patients with ACE inhibitor-induced angioedema. Ann Pharmacother. 2000; 34:526-8. [IDIS 443518] [PubMed 10772441]

8. Zuschke CA, Keys I, Munger MA et al. (Candesartan Cilexetil Study Investigators.) Candesartan cilexetil: comparison of once-daily versus twice-daily administration for systemic hypertension. Candesartan Cilexetil Study Investigators. Clin Ther. 1999; 21:464-74. [IDIS 427445] [PubMed 10321416]

9. Unger T. Significance of angiotensin type 1 receptor blockade: why are angiotensin II receptor blockers different? Am J Cardiol. 1999; 84:9-15S.

10. Martineau P, Goulet J. New competition in the realm of renin-angiotensin axis inhibition; the angiotensin II receptor antagonists in congestive heart failure. Ann Pharmacother. 2001; 35:71-84. [IDIS 457649] [PubMed 11197588]

11. Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure. The fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC V). Arch Intern Med. 1993; 153:154-83. [IDIS 309043] [PubMed 8422206]

12. US Food and Drug Administration. Dangers of ACE inhibitors during second and third trimesters of pregnancy. FDA Med Bull. 1992; 22:2.

13. Mazzolai L, Burnier M. Comparative safety and tolerability of angiotensin II receptor antagonists. Drug Safety. 1999; 21:23-33. [PubMed 10433351]

14. Kirk JK. Therapy with angiotensin II receptor antagonists. Clin Geriatrics. From the MultiMedia Health Care website: ().

15. Velasquez MT. Angiotensin II receptor blockers: a new class of hypertensive drugs. Arch Fam Med. 1996; 5:351-356. [PubMed 8640326]

16. Sever P, Holzgreve H. Long-term efficacy and tolerability of candesartan cilexetil in patients with mild to moderate hypertension. J Hum Hypertens. 1997; 11(Suppl 2):S69-73. [PubMed 9331014]

17. Zanchetti A, Omboni S, for the Italian Candesartan Study Group. Comparison of candesartan versus enalapril in essential hypertension. Am J Hypertens. 2001; 14:129-34. [PubMed 11243303]

18. Franke H. Antihypertensive effects of candesartan cilexetil, enalapril and placebo. J Hum Hypertens. 1997; 11(Suppl 2):S61-2. [PubMed 9331010]

19. Zanchetti A, Omboni S, Di Biagio C. Candesartan cilexetil and enalapril are of equivalent efficacy in patients with mild to moderate hypertension. J Hum Hypertens. 1997; 11(Suppl 2):S57-9. [PubMed 9331009]

20. Reif M, White WB, Fagan T et al. Effects of candesartan cilexetil in patients with systemic hypertension. Am J Cardiol. 1998; 82:961-5. [IDIS 415989] [PubMed 9794352]

21. Papademetriou V, Reif M, Henry D et al. Combination therapy with candesartan cilexetil and hydrochlorothiazide in patients with systemic hypertension. J Clin Hypertens. 2000; 2:372-8.

22. Buter H, Navis GY, Woittiez AJJ et al. Pharmacokinetics and pharmacodynamics of candesartan cilexetil in patients with normal to severely impaired renal function. Eur J Clin Pharmacol. 1999; 54:953-8. [IDIS 424653] [PubMed 10192757]

23. de Zeeuw D, Remuzzi G, Kirch W. Pharmacokinetics of candesartan cilexetil in patients with renal or hepatic impairment. J Hum Hypertens. 1997; 11(Suppl 2):S37-42. [PubMed 9331004]

24. AstraZeneca, Wayne, PA: Personal communication.

25. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care. 2002; 25:134-47. [IDIS 479088] [PubMed 11772914]

26. Brenner BM, Cooper ME, de Zeeuw D et al. Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001; 345:861-9. [IDIS 469607] [PubMed 11565518]

27. Lewis EJ, Hunsicker LG, Claarke WR et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001; 345:851-60. [IDIS 469606] [PubMed 11565517]

28. Sica DA, Bakris GL. Type 2 diabetes: RENAAL and IDNT—the emergence of new treatment options. J Clin Hypertens (Greenwich). 2002; 4:52-7. [PubMed 11821641]

29. Parving HH, Brenner BM, Cooper ME et al. [Effect of losartan on renal and cardiovascular complications of patients with type 2 diabetes and nephropathy.] (Danish; with English abstract.) Ugeskr Laeger. 2001; 163:5514-9.

30. Weekers L, Krzesinski JM. [Clinical study of the month. Nephroprotective role of angiotensin II receptor antagonists in typre 2 diabetes: results of IDNT and RENAAL trials.] (French; with English abstract.) Rev Med Liege. 2001; 56:723-6.

31. Parving HH, Lehnert H, Brochner-Mortensen J et al and the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med. 2001; 345:870-8. [IDIS 469608] [PubMed 11565519]

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