Nisoldipine

Pronunciation

(NYE sole di peen)

U.S. Brand Names

Sular®

Generic Available

Use

Management of hypertension, alone or in combination with other antihypertensive agents

Pregnancy Risk Factor

Lactation

Excretion in breast milk unknown

Contraindications

Hypersensitivity to nisoldipine, any component of the formulation, or other dihydropyridine calcium channel blockers

Warnings/Precautions

Increased angina and/or myocardial infarction in patients with coronary artery disease. Use with caution in patients with hypotension, CHF, and hepatic impairment. Blood pressure lowering must be done at a rate appropriate for the patient's condition.

Adverse Reactions

>10%:

Cardiovascular: Peripheral edema (dose related 7% to 29%)

Central nervous system: Headache (22%)

1% to 10%:

Cardiovascular: Chest pain (2%), palpitation (3%), vasodilation (4%)

Central nervous system: Dizziness (3% to 10%)

Dermatologic: Rash (2%)

Gastrointestinal: Nausea (2%)

Respiratory: Pharyngitis (5%), sinusitis (3%), dyspnea (3%), cough (5%)

<1% (Limited to important or life-threatening): Cellulite, chills, facial edema, fever, flu syndrome, malaise, atria fibrillation, CVA, CHF, first-degree AV block, hypertension, angina, pulmonary edema, jugular venous distention, migraine, MI, postural hypertension, ventricular extrasystoles, supraventricular tachycardia, syncope, systolic ejection murmur, T-wave abnormalities on ECG (flattening, inversion, nonspecific changes), venous insufficiency, abnormal liver function tests, anorexia, colitis, diarrhea, dry mouth, dyspepsia, dysphagia, flatulence, gastritis, gastrointestinal hemorrhage, gingival hyperplasia, glossitis, hepatomegaly, increased appetite, melena, mouth ulceration, diabetes mellitus, thyroiditis, anemia, ecchymoses, leukopenia, petechiae, gout, hypokalemia, increased serum creatine kinase, increased nonprotein nitrogen, weight gain, weight loss, arthralgia, arthritis, leg cramps, myalgia, myasthenia, myositis, tenosynovitis, abnormal dreams, abnormal thinking and confusion, amnesia, anxiety, ataxia, cerebral ischemia, decreased libido, depression, hypesthesia, hypertonia, insomnia, nervousness, paresthesia, somnolence, tremor, vertigo, asthma, dyspnea, end inspiratory wheeze and fine rales, epistaxis, increased cough, laryngitis, pharyngitis, pleural effusion, rhinitis, sinusitis, acne, alopecia, dry skin, exfoliative dermatitis, fungal dermatitis, herpes simplex, herpes zoster, maculopapular rash, pruritus, pustular rash, skin discoloration, skin ulcer, diaphoresis, urticaria, 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, watery eyes, dysuria, hematuria, impotence, nocturia, urinary frequency, increased BUN and serum creatinine, vaginal hemorrhage, vaginitis, gynecomastia

Case report: Cholestatic jaundice

Overdosage/Toxicology

Primary cardiac symptoms of calcium blocker overdose include hypotension and bradycardia. Noncardiac symptoms include confusion, stupor, nausea, vomiting, metabolic acidosis and hyperglycemia. Treat symptomatically.

Drug Interactions

Substrate of CYP3A4 (major); Inhibits CYP1A2 (weak), 3A4 (weak)

Azole antifungals may inhibit the calcium channel blocker's metabolism; avoid this combination. Try an antifungal like terbinafine (if appropriate) or monitor closely for altered effect of the calcium channel blocker.

Beta-blockers may have increased pharmacokinetic or pharmacodynamic interactions with nisoldipine.

Calcium may reduce the calcium channel blocker's effects, particularly hypotension.

CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of nisoldipine. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.

CYP3A4 inhibitors: May increase the levels/effects of nisoldipine. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and verapamil.

Grapefruit juice increases the bioavailability of nisoldipine; monitor for altered nisoldipine effects.

Phenytoin decreases nisoldipine to undetectable levels. Avoid use of any CYP3A4 inducer with nisoldipine.

Rifampin increases the metabolism of the calcium channel blocker; adjust the dose of the calcium channel blocker to maintain efficacy.

Sildenafil, tadalafil, vardenafil: Blood pressure-lowering effects may be additive; use caution.

Ethanol/Nutrition/Herb Interactions

Food: Nisoldipine bioavailability may be increased if taken with high-lipid foods or with grapefruit juice. Avoid grapefruit products before and after dosing.

Herb/Nutraceutical: St John's wort may decrease nisoldipine levels. Avoid dong quai if using for hypertension (has estrogenic activity). Avoid ephedra, yohimbe, ginseng (may worsen hypertension). Avoid garlic (may have increased antihypertensive effect).

Mechanism of Action

As a dihydropyridine calcium channel blocker, structurally similar to nifedipine, nisoldipine impedes the movement of calcium ions into vascular smooth muscle and cardiac muscle. Dihydropyridines are potent vasodilators and are not as likely to suppress cardiac contractility and slow cardiac conduction as other calcium antagonists such as verapamil and diltiazem; nisoldipine is 5-10 times as potent a vasodilator as nifedipine.

Pharmacodynamics/Kinetics

Duration: >24 hours

Absorption: Well absorbed

Metabolism: Extensively hepatic to inactive metabolites; first-pass effect

Bioavailability: 5%

Half-life elimination: 7-12 hours

Time to peak: 6-12 hours

Excretion: Urine

Dosage

Adults: Oral: Initial: 20 mg once daily, then increase by 10 mg/week (or longer intervals) to attain adequate control of blood pressure; usual dose range (JNC 7): 10-40 mg once daily; doses >60 mg once daily are not recommended. A starting dose not exceeding 10 mg/day is recommended for the elderly and those with hepatic impairment.

Administration

Administer at the same time each day to ensure minimal fluctuation of serum levels. Avoid high-fat diet.

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take exactly as directed; do not alter dose or decrease without consulting prescriber. Do not crush or chew capsules; swallow whole. Take with food, but avoid fatty food and grapefruit juice. This drug does not replace diet and other exercise recommendations of prescriber. May cause orthostatic hypotension (change position slowly when rising from sitting or lying, or when climbing stairs); headache (consult prescriber for approved analgesic); dizziness (use caution when driving or engaging in tasks that require alertness until response to drug is known); or nausea (small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report chest pain, palpitations, irregular heartbeat; respiratory difficulty; unusual cough; rash; vision changes; anxiety, confusion, depression, or other CNS changes; or other persistent adverse reactions. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.

Cardiovascular Considerations

Nisoldipine alone or in combination with other agents is effective in the management of hypertension and angina. Nisoldipine should be avoided in patients with left ventricular systolic dysfunction because of negative inotropic effects.

In the treatment of unstable angina/non-ST-segment elevation MI, a nondihydropyridine calcium antagonist (diltiazem or verapamil) may be considered in patients with continuing or frequently recurring ischemia when beta-blockers are contraindicated (Class I). Oral long-acting calcium antagonists may also be considered in addition to beta-blockers and nitrates (Class IIa).

Dental Health: Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

May cause dizziness

Mental Health: Effects on Psychiatric Treatment

None reported

Dosage Forms

Tablet, extended release: 10 mg, 20 mg, 30 mg, 40 mg

References

Braunwald E, Antman EM, Beasley JW, et al, "ACC/AHA Guidelines for the Management of Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina)," J Am Coll Cardiol , 2000, 36(3):970-1062.

Chobanian AV, Bakris GL, Black HR, et al, "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report," JAMA , 2003, 289(19):2560-71.

Estacio RO, Jeffers BW, Hiatt WR, et al, "The Effect of Nisoldipine as Compared With Enalapril on Cardiovascular Outcomes in Patients With Noninsulin-Dependent Diabetes and Hypertension," N Engl J Med , 1998, 338(10):645-52.

International Brand Names

Baymycard CC® (HU); Baymycard® (DE, HU, RO); Corasol® (CL); Cornel® (ES); Nivas® (CL); Nizoldin® (YU); Sular® (BE, ES, MX, NL); Syscor® (AT, BE, ES, FI, GB, IT, LU, MX, NL, PL, TR, ZA)

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