Prior Authorization Guideline Guideline: Cover Colorado - Aceon, Mavik Therapeutic Class: Cardiovascular Agents Therapeutic Sub-Class: ACE Inhibitors Client: CC Approval Date: 1/1/2006 Revision Date: I. BENEFIT COVERAGE Table 1. Formulary status Non-Formulary Products Aceon (Perindopril)* Mavik (Trandolapril)* Formulary Products Accupril (Quinapril) Altace (Ramipril) Capoten (Captopril) Lotensin (Benazepril) Monopril (Fosinopril) Vasotec (Enalapril) Zestril (Lisinopril) Univasc (Moexipril) *Subject to Prior Authorization FDA Approved Indication(s): ACE inhibitors are indicated for the treatment of hypertension, either alone or in combination with other antihypertensive agents. ACE inhibitors may be used as initial therapy in hypertensives with congestive heart failure (CHF), diabetes mellitus or renal impairment. See Table 1 for list of FDA approved indications Table 2: FDA Approved Indications HTN Heart Failure Accupril Aceon Altace Capoten Lotensin Mavik Monopril Univasc Vasotec Zestril ♥ X X X X X X X X X X Myocardial Infarction Left Ventricular Dysfunction Diabetic Neuropathy X♥ X X X♥ X♥ X X♥ X X X X Post MI Guideline(s): I. Aceon or Mavik will be approved based on one of the following criteria: A. As continuation of therapy -OR- B. Contraindication, intolerance or history of failure to at least one (1) formulary agent Contraindications: • Angioedema with previous ACE inhibitor: ACE inhibitors are contraindicated in patients with history of angioedema related to previous treatment with an ACE inhibitor. • Pregnancy: ACE inhibitors are contraindicated in pregnancy. (Category C first trimester, and Category D second and third trimesters). When pregnancy is detected, discontinue the ACE inhibitor as soon as possible. Warnings: • Neutropenia/agranulocytosis has been associated with the use of Captopril, and rarely with enalapril or lisinopril, and in one patient on quinapril. Most cases are reversible upon withdrawl of the drug, however, fatalties have resulted in patients with pre-existing serious illness such as collagen vascular disease, renal failure, heart failure, or immunosuppressant therapy. • Angioedema has occurred in patients treated with ACE inhibitors. It may occur at any time during treatment. Angioedema associated with laryngeal edema may be fatal. Patients with history of angioedema unrelated to ACE inhibitor therapy may be at increased risk. Black patients receiving ACE inhibitor monotherapy have been reported to have a higher incidence of angioedema than non-blacks. • Proteinuria of >1 gm urinary proteins/day has been associated with captopril, (0.7% of patients). Nephrotic syndrome occuredd in 20% of cases. In most cases, proteinuria cleared within 6 months, regardless if captopril was continued. • Hypotension: ACE inhibitors may cause a profound fall in blood pressure following the first dose, especially in patients who are salt/volume depleted or treated with diuretics. • Renal Function Impairment: Increases in BUN and serum creatinine have been reported in hypertensives with unilateral or bilateral renal artery stenosis in 20% of patients on enalapril. Twenty percent of patients on long-term captopril therapy with heart failure develop stable elevations in BUN and creatinine of >20% from baseline. • Hepatic Function Impairment: Rarely ACE inhibitors have been associated with a syndrome of cholestatic jaundice progressing to fulminant hepatic necrosis and possible death. Patients who develop jaundice or marked elevations in liver enzymes should discontinue the ACE inhibitor therapy. • Lactation: Do not administer trandolapril (Mavik®) or ramipril (Altace®) to nursing mothers. It is not know if lisinopril (Zestril®) or moexipril (Univasc®) is excreted in breast milk. • Children: Safety and efficacy have not been established. However, there is limited experience with Captopril in children. Dosage, on a weight basis, is comparable to or less than that used in adults. Dosing Recommendation(s): Comparative Dosing for hypertension Medication Accupril Aceon Initial Dose∗ 10 mg QD 4 mg QD Dosage Range∗ 10-80 mg/day 4-8 mg/day Altace Capoten Lotensin Mavik Monopril Univasc Vasotec Zestril 2.5 mg QD 25 mg BID/TID 10 mg QD 1 mg QD 10 mg QD 7.5 mg QD 5 mg QD 10 mg QD 2.5-20 mg/day 25-150 mg BID/TID 10-80 mg/day 2-4 mg/day 10-80 mg/day 7.5-30 mg/day 10-40 mg/day 10-80 mg/day ∗ Dosing recommendations are for treatment of hypertension in patients with normal renal function not receiving a diuretic. For patients on a diuretic, start with half the recommended initial dose. Comparative Dosing for CHF Medication Accupril Altace Capoten Monopril Vasotec Zestril Initial Dose 5 mg BID 2.5mg BID 25 mg TID♦ 10 mg QD 2.5 mg QD/BID 5 mg QD Dosage Range 10-40 mg/day 1.25mg-5 mg/day 150-450 mg/day 20-40 mg/day 10-40 mg/day 5-20 mg/day ♦ Lower doses (6.25 to 12.5 milligrams 3 times daily) may minimize the hypotensive effect in patients with normal or low blood pressure and those who may be hyponatremic and/or hypovolemic (Packer & Cohn, 1999; Prod Info Capoten(R), 2000; Lang et al, 1994. Table 3 : RENAL IMPAIRMENT DOSAGE RECOMMENDATIONS DRUG CrCl Initial Dose Recommended > 75 mL/min 25 mg Capoten (Captopril) 35 - 75 mL/min. 25 mg 20 - 34 mL/min 25 mg 8 - 19 mL/min 25 mg 5 - 7 mL/min 25 mg > 60 mL/min. 10 mg Lotensin (Benazepril) 30 - 60 mL/min 10 mg 10 - 30 mL/min 5 mg < 10 5 mg 3.75 mg Univasc (Moexipril) ≤ 40 mL/min  > 30 mL/min 10 mg Zestril (Lisinopril) 10 - 30 mL/min 5 mg < 10 mL/min 2.5 mg Interval q8h q12h to q24h q24h to q48h q48h to q72h q72 to q108h q24h q24h q24h q24h q24h q24h q24h q24h References: 1. Micromedex Inc.,2001. 2. Drug Facts and Comparisons, February 2001. 3. AHFS Drug Information, 2001. 4. The HOPE study investigators, Effects of an angiotensin coverting-enzyme inhibitor, ramipril, on cardiovascular events in high risk patients. NEJM 2000;342:145-153. 5. Heel RC, Brogden RN, Speight TM et al: Captopril: a preliminary review of its pharmacological properties and therapeutic efficacy. Drugs 1980; 20:409-452. 6. Sica DA, Gehr TWB & Fernandez A: Risk-benefit ratio of angiotensin antagonists versus ACE inhibitors in end-stage renal disease. Drug Saf 2000; 22(5):350-360. 7. 8. 9. 10. Zestril (lisinopril), Product info AstraZeneca, February 2000. Univasc (moexipril), Product info Schwarz, February 2000. Lotensin (benzepril), Product info Novartis, May 2000. Capoten (captopril), Product info Bristol-Myers Squibb, 9/2000. This Prior Authorization Guideline represents the recommendation of Prescription Solutions’ Pharmacy and Therapeutics (P&T) Committee. It is based upon the P&T Committee’s review of the available evidence as of the date of drafting or revision of this Prior Authorization Guideline. It is subject to updating from time to time, based upon changes in scientific knowledge and information. This Prior Authorization Guideline is intended as a resource for making coverage decisions for Health Plan members, but it does not replace an individualized case-by-case review and medical necessity determination for each Health Plan member. Copyright © 2005 by Prescription Solutions. All rights reserved. This Prior Authorization Guideline is intended for use by Prescription Solutions and Health Plan employees and applicable contracted providers and practitioners only. The information contained in this Prior Authorization Guideline is confidential and proprietary to Prescription Solutions and shall not be used, reproduced, or transferred in whole or in part without Prescription Solutions’ prior written consent.