BY DREW BUONO
ST. LOUIS — Experts from the Food and Drug Admini-
stration, National Library of Medicine, universities, corporations and nonprofit organizations convened at
the St. Louis College of Pharmacy in April to examine trends related to the safe use and distribution of pharma-
ceuticals at the St. Louis Forum on Medication Safety.
“The medication safety forum provided an oppor-
DESCRIPTION
SULAR® (nisoldipine) is an extended release tablet dosage form of the dihydropyridine calcium channel blocker nisoldipine. SULAR tablets contain either 8.5, 17, 25. 5, or 34 mg of nisoldipine for once-a-day oral administration.
INDICATIONS AND USAGE
SULAR is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.
(Rates in %)
Peripheral Edema
Dizziness
Placebo
N=280
10
4
8.5 mg
N= 30
7
7
17 mg
N=170
15
3
25. 5 mg
N=105
20
3
34 mg
N=139
27
4
CONTRAINDICATIONS
SULAR is contraindicated in patients with known hypersensitivity to dihydropyridine calcium channel blockers.
The common adverse events occurred at about the same rate in men as in women, and at a similar rate in patients over age 65 as in those in under that age, except that headache was much less common in older patients. Except for peripheral edema and vasodilation, which were more common in whites, adverse event rates were similar in blacks and whites.
WARNINGS
Increased angina and/or myocardial infarction in patients with coronary artery disease: Rarely, patients, particularly those with severe obstructive coronary artery disease, have developed increased frequency, duration and/or severity of angina, or acute myocardial infarction on starting calcium channel blocker therapy or at the time of dosage increase. The mechanism of this effect has not been established. In controlled studies of SULAR in patients with angina this was seen about 1.5% of the time in patients given nisoldipine, compared with 0.9% in patients given placebo.
The following adverse events occurred in <1% of all patients treated for hypertension in U.S. and foreign clinical trials, or with unspecified incidence in other studies. Although a causal relationship of SULAR to these events cannot be established, they are listed to alert the physician to a possible relationship with SULAR treatment.
Body As A Whole: cellulitis, chills, facial edema, fever, flu syndrome, malaise
PRECAUTIONS
General
Hypotension: Because nisoldipine, like other vasodilators, decreases peripheral vascular resistance, careful monitoring of blood pressure during the initial administration and titration of SULAR is recommended. Close observation is especially important for patients already taking medications that are known to lower blood pressure. Although in most patients the hypotensive effect of SULAR is modest and well tolerated, occasional patients have had excessive and poorly tolerated hypotension. These responses have usually occurred during initial titration or at the time of subsequent upward dosage adjustment.
Cardiovascular: atrial fibrillation, cerebrovascular accident, congestive heart failure, first degree AV block, hypertension, hypotension, jugular venous distension, migraine, myocardial infarction, postural hypotension, ventricular extrasystoles, supraventricular tachycardia, syncope, systolic ejection murmur, T wave abnormalities on ECG (flattening, inversion, nonspecific changes), venous insufficiency
Digestive: abnormal liver function tests, anorexia, colitis, diarrhea, dry mouth, dyspepsia, dysphagia, flatulence, gastritis, gastrointestinal hemorrhage, gingival hyperplasia, glossitis, hepatomegaly, increased appetite, melena, mouth ulceration.
Endocrine: diabetes mellitus, thyroiditis
Congestive Heart Failure: Although acute hemodynamic studies of nisoldipine in patients with N YHA Class II-IV heart failure have not demonstrated negative inotropic effects, safety of SULAR in patients with heart failure has not been established. Caution therefore should be exercised when using SULAR in patients with heart failure or compromised ventricular function, particularly in combination with a beta-blocker.
Hemic and Lymphatic: anemia, ecchymoses, leukopenia, petechiae
Metabolic and Nutritional: gout, hypokalemia, increased serum creatine kinase, increased nonprotein nitrogen, weight gain, weight loss
Patients with Hepatic Impairment: Because nisoldipine is extensively metabolized by the liver and, in patients with cirrhosis, it reaches blood concentrations about 5 times those in normals, SULAR should be administered cautiously in patients with severe hepatic dysfunction (See DOSAGE AND ADMINIS TRATION).
Musculoskeletal: arthralgia, arthritis, leg cramps, myalgia, myasthenia, myositis, tenosynovitis
ADVERSE EXPERIENCES
More that 6000 patients world-wide have received nisoldipine in clinical trials for the treatment of hypertension, either as the immediate release or the SULAR extended release formulation. Of about 1,500 patients who received SULAR in hypertension studies, about 55% were exposed for at least 2 months and about one third were exposed for over 6 months, the great majority at doses equivalent to 17 mg and above.
Nervous: abnormal dreams, abnormal thinking and confusion, amnesia, anxiety, ataxia, cerebral ischemia, decreased libido, depression, hypesthesia, hypertonia, insomnia, nervousness, paresthesia, somnolence, tremor, vertigo
Respiratory: asthma, dyspnea, end inspiratory wheeze and fine rales, epistaxis, increased cough, laryngitis, pharyngitis, pleural effusion, rhinitis, sinusitis
SULAR is generally well-tolerated. In the U. S. clinical trials of SULAR in hypertension, 10.9% of the 921 SULAR patients discontinued treatment due to adverse events compared with 2.9% of 280 placebo patients. The frequency of discontinuations due to adverse experiences was related to dose, with a 5.4% and 10.9% discontinuation rate at the lowest and highest daily dose, respectively.
Skin and Appendages: acne, alopecia, dry skin, exfoliative dermatitis, fungal dermatitis, herpes simplex, herpes zoster, maculopapular rash, pruritus, pustular rash, skin discoloration, skin ulcer, sweating, urticaria
Special Senses: abnormal vision, amblyopia, blepharitis, conjunctivitis, ear pain, glaucoma, itchy eyes, keratoconjunctivitis, otitis media, retinal detachment, tinnitus, watery eyes, taste disturbance, temporary unilateral loss of vision, vitreous floater
The most frequently occurring adverse experiences with SULAR are those related to its vasodilator properties; these are generally mild and only occasionally lead to patient withdrawal from treatment. The table below, from U.S. placebo-controlled parallel dose response trials of SULAR using doses across the clinical dosage range in patients with hypertension, lists all of the adverse events, regardless of the causal relationship to SULAR, for which the overall incidence on SULAR was both>1% and greater with SULAR than with placebo.
Urogenital: dysuria, hematuria, nocturia, urinary frequency, increased BUN and serum creatinine, vaginal hemorrhage, vaginitis
Adverse Event
Nisoldipine (%) (n=663)
22
Placebo (%) (n=280)
The following postmarketing event has been reported very rarely in patients receiving SULAR: systemic hypersensitivity reaction, which may include one or more of the following: angioedema, shortness of breath, tachycardia, chest tightness, hypotension, and rash. A definite causal relationship with SULAR has not been established. An unusual event observed with immediate release nisoldipine but not observed with SULAR was one case of photosensitivity. Gynecomastia has been associated with the use of calcium channel blockers.
Peripheral Edema
10
Rx Only
Headache
22
15
Dizziness
5
4
SULAR® is a trademark of Sciele Pharma, Inc. ©2003 Sciele Pharma, Inc.
Pharyngitis
5
4
Vasodilation
4
2
Manufactured for: Sciele Pharma, Inc Atlanta, GA 30328
Sinusitis
3
2
Palpitation
3
1
By: SkyePharma Production SAS SLG-PI- 04 Rev 01/08
38291 Saint Quentin-Fallavier, France
Made in France
Chest Pain
2
1
Code 34EP5986C
Nausea
2
1
Rash
2
1
tunity to specifically discuss patient and drug safety issues in the United States,” said Thomas Patton, president of the college. “It incorporated a team-oriented approach between academic scholars, practitioners, government agencies and industry leaders to discuss initiatives and best practices to benefit health care and all patients who utilize and depend on our services.”
Three panel discussions took place, focusing on methods for using technology to reduce medication errors, detecting concerns and issues in the nation’s drug supply, and trends in health education among Americans. Experts discussed government and industry collaborations, initiatives and technologies that dealt with safety. Additionally, they explored medication usage by examining how patients follow physician and pharmacist instructions, monitor potential side effects and negative interactions, and properly store their medications.
“Medication safety focuses on two primary areas: one is the minimization of adverse drug reactions, and the other is the prevention of medication errors,” said Wendy Duncan-Hewitt, dean of pharmacy and vice president for academic affairs at the college. “As healthcare professionals— whether in a classroom setting developing new technologies, or directly assisting patients each day—we must collaborate to remain up-to-date on policies, procedures and practices that ultimately ensure patient safety. Healthcare practitioners in St. Louis, as well as throughout the nation, have an important role to play, and this forum is part of that increasingly important process.”
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