March 2003

FORMULARY ADDITIONS

Tegaserod Maleate

(Zelnorm^Ô)

2 mg and 6 mg tablets

Tegaserod is a serotonin Type-4 (5-HT₄) receptor partial agonist that binds with high affinity at human 5-HT₄ receptors. It is indicated for the short-term treatment of women with irritable bowel syndrome (IBS) whose primary bowel symptom is constipation. By activating 5-HT₄ receptors in the gastrointestinal tract, tegaserod stimulates the peristaltic reflex and intestinal secretion, as well as inhibits visceral sensitivity.

Tegaserod is contraindicated in those patients with severe renal impairment, moderate or severe hepatic impairment, a history of bowel obstruction, symptomatic gallbladder disease, suspected sphincter of Oddi dysfunction, abdominal adhesions, or a known hypersensitivity to the drug or any of its excipients.

Tegaserod should not be initiated in patients who are currently experiencing or frequently experience diarrhea. Tegaserod should be discontinued immediately in patients with new or sudden worsening of abdominal pain. In clinical studies, 8.8% of patients receiving tegaserod reported diarrhea as an adverse experience compared to 3.8% of patients receiving placebo. The majority of the tegaserod patients reporting diarrhea had a single episode. In most cases, diarrhea occurred within the first week of treatment. Typically, resolution occurred with continued therapy.

DRUG AND FOOD INTERACTIONS: Tegaserod should be administered without food, either one hour before or two to three hours following a meal.

DOSAGE AND ADMINISTRATION:

The recommended dosage of tegaserod is 6 mg taken twice daily orally before meals for 4 to 6 weeks. For those patients who respond to therapy at 4-6 weeks, an additional 4-6 week course can be considered.

Aspirin/Extended-Release Dipyridamole

(Aggrenox^Ô)

25 mg/200 mg Extended Release Capsules

Aspirin 25 mg/extended-release dipyridamole 200 mg capsules are approved for the reduction of the risk of stroke in patients who have had transient ischemia of the brain or completed ischemic stroke due to thrombosis.

Aggrenox is contraindicated in patients with known hypersensitivity reactions to aspirin, nonsteroidal anti-inflammatory agents, dipyridamole, acacia, aluminum stearate, colloidal silicon dioxide, corn starch, dimethicone, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, lactose monohydrate, methacrylic acid copolymer, microcrystalline cellulose, povidone, stearic acid, sucrose, talc, tartaric acid, titanium dioxide, triacetin, red iron oxide, and yellow iron oxide. It should also be avoided in patients with the syndrome of asthma, rhinitis, and nasal polyps and, to avoid the development of Reye’s syndrome, in children or teenagers with viral infections. The risk of bleeding may be increased in patients who consume three or more alcoholic beverages every day and patients with inherited or acquired bleeding disorders (e.g., liver disease and vitamin K deficiency).

Gastrointestinal side effects (e.g., stomach pain, heartburn, nausea, vomiting, and GI bleeding) may occur in patients treated with aspirin 25 mg/extended-release dipyridamole 200 mg. Patients should be monitored for the development of ulceration and bleeding while using aspirin 25 mg/extended-release dipyridamole 200 mg. Patients with a history of peptic ulcer disease are at increased risk. Chest pain may be aggravated by the use of Aggrenox in patients with unstable angina, recent myocardial infarction, and other forms of severe coronary artery disease.

The dose of aspirin in aspirin 25 mg/extended-release dipyridamole 200 mg may be insufficient to prevent recurrent myocardial infarction or angina pectoris. Aggrenox should be used with caution in patients with hepatic insufficiency, hypotension, and renal dysfunction. Aspirin should be avoided in patients with severe hepatic insufficiency or renal failure. Therefore, aspirin 25 mg/extended-release dipyridamole 200 mg should be also be avoided in these patients.

Aggrenox therapy has been associated with elevated hepatic enzymes, blood urea nitrogen, serum creatinine, hyperkalemia, proteinuria, and prolonged bleeding time. The most common adverse effects associated with aspirin 25 mg/extended-release dipyridamole 200 mg therapy included headache, dyspepsia, abdominal pain, nausea, diarrhea, and vomiting. The incidence of reactions with this product is not significantly different from those reported with the individual agents. No drug interaction studies have been conducted with the aspirin 25 mg/extended-release dipyridamole 200 mg formulation. All reported drug interactions in the product labeling are based on those reported with aspirin or dipyridamole therapy alone.

DRUG AND FOOD INTERACTIONS: The manufacturer's prescribing information lists no food/drug interactions.

DOSAGE AND ADMINISTRATION:

Aspirin 25 mg/extended-release dipyridamole 200 mg capsules should be given orally twice daily, in the morning and evening. Each capsule should be swallowed whole and should not be crushed or chewed. The daily dose of aspirin contained in the Aggrenox formulation is within the ranges recommended by the Ad Hoc Committee on Guidelines for the Management of Transient Ischemic Attacks, Stroke Council, American Heart Association.

Dutasteride (Avodart^Ô)

0.5 mg soft gelatin capsule

Dutasteride, a synthetic 4-azasteroid compound, is indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to improve symptoms, reduce the risk of acute urinary retention, and reduce the risk of need for BPH-related surgery.

Dutasteride is contraindicated in women and children, and should be avoided in patients with known hypersensitivity reactions to dutasteride, other 5a-reductase inhibitors, or any component of the product formulation (hydrous lactose, microcrystalline cellulose, pregelatinized starch, sodium starch glycolate, hydroxypropyl cellulose LF, hydroxypropylmethyl cellulose, titanium dioxide, magnesium stearate, talc, docusate sodium, FD&C Blue 2 aluminum lake and yellow iron oxide). Dutasteride is classified as Pregnancy Category X. Fetal anomaly may occur in male fetuses. Women who are pregnant or may be pregnant should not handle the capsules since dutasteride is absorbed through the skin. In general, women should handle the capsules with caution, and wash affected areas with soap and water if contact is made with leaking capsules.

A digital rectal examination and other evaluations for prostate cancer should be performed prior to initiating therapy and periodically thereafter. Patients with large residual urinary volume and/or severely diminished urinary flow are not good candidates. If therapy is started, they need to be monitored for obstructive uropathy. Blood donations should also be avoided during dutasteride therapy and for at least 6 months after discontinuation. Caution is advised in patients with hepatic dysfunction and

carcinogenesis is a risk with dutasteride therapy.

Most adverse effects occurring during dutasteride therapy are mild and transient. The most frequent adverse effects included impotence (4.7%), decreased libido (3%), ejaculation disorders (1.4%), and gynecomastia/breast tenderness/breast enlargement (1%). Most of these adverse events occurred more frequently during the first year of therapy. The incidences of other adverse effects (e.g., ENT infections, musculoskeletal pain) are equal or less than placebo. The adverse effects leading to withdrawal of dutasteride therapy are associated with the reproductive system.

In vitro studies indicate that drugs (e.g., ritonavir, ketoconazole, verapamil, diltiazem, cimetidine, ciprofloxacin) that inhibit the CYP3A4 isozyme may decrease the metabolism of dutasteride and increase its serum concentration. Caution is advised in patients receiving concomitant potent CYP3A4 inhibitors. Amlodipine therapy causes a small increase (7%) in clearance. No pharmacokinetic or pharmacodynamic drug interactions have been observed with tamsulosin, terazosin, warfarin, digoxin, or cholestyramine.

DRUG AND FOOD INTERACTIONS: The manufacturer's prescribing information lists no food/drug interactions.

DOSAGE AND ADMINISTRATION:

The recommended dose of dutasteride is 0.5 mg orally once a day. The capsules should be swallowed whole and not broken or chewed. No dosage adjustments are currently recommended for elderly patients or patients with renal or hepatic dysfunction.

Formulary Additions and Deletions Not Listed in 2002-2003 Formulary Publication
Generic Name	Trade Name	Therapeutic Class	Action	Date	Comments
Alendronate once-weekly	Fosamax	Bisphosphonate	Added	6/25/02
Amphotericin B Suspension	Fungizone	Antifungal	Deleted	1/8/02	Discontinued by manufacturer
Antithymocyte Globulin (rabbit)	Thymoglobulin	Immunosuppressant	Added	3/28/01
Aspirin/Dipyridamole	Aggrenox	Antiplatelet Agent	Added	2/25/03
Bosentan	Tracleer	Pulmonary hypertension agent	Added	8/21/02	Restricted to pulmonary services
Brimonidine	Alphagan	Ophthalmic agent	Added	8/21/02
Camphorated Tincture of Opium	Paregoric	Analgesic	Deleted	10/11/02	Discontinued by manufacturer
Colchicine 0.5mg	Colchicine	Antigout	Deleted	1/22/02
Colchicine 0.6mg	Colchicine	Antigout	Added	1/2202
Dexmedetomidine	Precedex	General anesthetic	Added	10/22/02
Dexamethasone-Neomycin Sulfate-Polymyxin B Sulfate Ophthalmic Solution	Dexacidin	Ophthalmic anti-inflammatory/antibiotic	Added	3/26/02
Docusate Compound Enema	Therevac-Plus		Deleted	8/7/02	Discontinued by manufacturer
Dutasteride	Avodart	BPH Agent	Added	2/25/03
Ertapenem	Invanz	Antibiotic	Added	3/26/02	Restricted to complicated/severe intra-abdominal infections and diabetic foot ulcers
Ethosuximide	Zarontin	Anticonvulsant	Deleted	6/25/02
Felbamate	Felbatol	Anticonvulsant	Deleted	6/25/02
Fenofibrate	Tricor	Antilipemic	Added	6/25/02
Fexofenadine	Allegra, Allegra-D	Antihistamine	Deleted	1/25/03
Fish Oil Concentrate		Dietary Supplement	Added	1/25/03
Fondaparin	Arixtra	Anticoagulant	Added	3/26//2	Restricted to Orthopedics
Hyaluronate/Chondroitin	Duovisc	Ophthalmic agent	Added	8/21/02
Hepatitis A Inactivatd and Hepatitis B-Recominant Vaccine	Twinrix	Vaccine	Added	10/11/02
Hydrocortisone-Neomycin Sulfate-Polymyxin B Sulfate Ophthalmic Solution	Cortisporin	Ophthalmic anti-inflammatory/antibiotic	Deleted	3/26/02
Insulin Lispro Mix	Humalog Mix 75/25	Insulin	Added	6/25/02
Ketoprofen	Orudis	Nonsteroidal anti-inflammatory	Deleted	6/25/02
Ketorolac Oral	Toradol	Nonsteroidal anti-inflammatory	Deleted	6/25/02	60 mg IV restricted to pharmacy compound use only
Lactobacillus GG	Culturelle	Dietary Supplement	Added	9/25/01
Levetiracetam	Keppra	Anticonvulsant	Added	6/25/02
Mefenamic Acid	Ponstel	Nonsteroidal anti-inflammatory	Deleted	6/25/02
Mephenytoin	Methoin	Anticonvulsant	Deleted	6/25/02
Moxifloxacin	Avelox	Antibiotic	Added	10/11/02
Mumps Skin Test Antigen	MSTA Mumps Skin Test Antigen	Diagnostic Agent	Deleted	2/3/03	Discontinued by manufacturer
Nesiritide	Natrecor	Natriuretic peptide for acutely decompensated congestive heart failure	Added	3/26/02	Restricted to cardiology consult
Oxaprozin	Daypro	Nonsteroidal anti-inflammatory	Deleted	6/25/02
Papain-Urea-Chlorophyllin Copper Complex Debriding Ointment	Panafil	Wound debridement	Added	3/26/02
Propranolol Sustained Release 60 mg	Inderal LA 60 mg	Antihypertensive Agent	Added	10/11/02
Sirolimus 1mg/ml Solution	Rapamune	Immunosuppressant Agent	Deleted	3/4/02	Discontinued by manufacturer
Tegaserod maleate	Zelnorm	Irritable Bowel Agent	Added	2/25/03
Theophylline IR (100mg & 200mg)	Slophyllin	Antiasthmatic	Deleted	3/4/02	Discontinued by manufacturer
Theophylline SR	Slo-bid	Antiasthmatic	Deleted	6/28/02	Discontinued by manufacturer
Thioridazine Suspension	Mellaril-S	Antipsychotic	Deleted	9/20/01
Tolazoline Hydrochloride	Priscoline	Vasodilator	Deleted	10/24/02	Discontinued by manufacturer
Treprostinil	Remodulin	Pulmonary hypertension agent	Added	8/21/02	Restricted to pulmonary services
Voriconazole	Vfend	Antifungal	Added	10/22/02	Restricted to order sheet
Ziprasidone IM	Geodon IM	Antipsychotic agent	Added	10/22/02	Restricted to psychiatry