Hypertension, chronic:
Note: For patients who warrant combination therapy (BP >20/10 mm Hg above goal or suboptimal response to initial monotherapy), may use in combination with another appropriate agent (eg, angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, thiazide diuretic) (ACC/AHA [Whelton 2018]).
Sular (Geomatrix delivery system): Oral: Initial: 17 mg once daily; evaluate response after ~2 to 4 weeks and titrate dose as needed by 8.5 mg/dose up to 34 mg once daily; antihypertensive effect attenuates with higher doses and adverse effects may become more prominent; if additional BP control is needed, consider combination therapy. Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (ACC/AHA [Whelton 2018]; Mann 2021).
Nisoldipine ER tablet (original formulation): Oral: Initial: 20 mg once daily; evaluate response after ~2 to 4 weeks and titrate dose as needed by 10 mg/dose up to 40 mg once daily; antihypertensive effect attenuates with higher doses and adverse effects may become more prominent; if additional BP control is needed, consider combination therapy. Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (ACC/AHA [Whelton 2018]; Mann 2021).
Conversion from nisoldipine extended release (original formulation) to Sular Geomatrix delivery system:
|
Original ER Formulation |
Sular Extended Release (Geomatrix delivery system) |
|---|---|
|
10 mg |
8.5 mg |
|
20 mg |
17 mg |
|
30 mg |
25.5 mg |
|
40 mg |
34 mg |
Mild to moderate impairment: No dosage adjustment necessary .
Severe impairment: No dosage adjustment provided in manufacturer's labeling.
Sular (Geomatrix delivery system): Oral: Initial dose should not exceed 8.5 mg once daily.
Nisoldipine extended release (original formulation): Oral: Initial dose should not exceed 10 mg once daily.
Hypertension:
Sular (Geomatrix delivery system): Oral: Initial dose: 8.5 mg once daily.
Nisoldipine extended release (original formulation): Oral: Initial dose: 10 mg once daily.
Conversion from nisoldipine extended release (original formulation) to Sular Geomatrix delivery system: Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Extended Release 24 Hour, Oral:
Sular: 8.5 mg
Sular: 17 mg [contains tartrazine (fd&c yellow #5)]
Sular: 34 mg
Generic: 8.5 mg, 17 mg, 20 mg, 25.5 mg, 30 mg, 34 mg, 40 mg
Yes
Oral: Administer at the same time each day to ensure minimal fluctuation of serum levels. Avoid high-fat diet. Administer on an empty stomach (1 hour before or 2 hours after a meal). Swallow whole; do not crush, break, split, or chew.
Bariatric surgery: Tablet, extended release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. No alternative formulations are available. If safety and efficacy of nifedipine can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, selection of alternative therapy should be considered for off-label variant angina indication.
Hypertension, chronic: Management of hypertension.
Nisoldipine may be confused with NIFEdipine, niMODipine
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Peripheral edema (7% to 29%; dose-related)
Central nervous system: Headache (22%)
1% to 10%:
Cardiovascular: Vasodilation (4%), palpitations (3%), exacerbation of angina pectoris (2%), chest pain (2%)
Central nervous system: Dizziness (3% to 10%)
Dermatologic: Skin rash (2%)
Gastrointestinal: Nausea (2%)
Respiratory: Pharyngitis (5%), sinusitis (3%)
<1%, postmarketing, and/or case reports: Abnormal dreams, abnormal hepatic function tests, abnormal T waves on ECG (flattening, inversion, non-specific changes), alopecia, amblyopia, amnesia, anemia, anorexia, anxiety, arthralgia, arthritis, asthma, ataxia, atrial fibrillation, blepharitis, bruise, cardiac failure (decompensated), cellulitis, cerebral ischemia, cerebrovascular accident, colitis, conjunctivitis, decreased libido, depression, dermal ulcer, diabetes mellitus, diaphoresis, diarrhea, drowsiness, dysgeusia, dyspepsia, dysphagia, dyspnea, dysuria, ejection murmur (systolic), epistaxis, exfoliative dermatitis, facial edema, fever, first degree atrioventricular block, flu-like symptoms, gastritis, gastrointestinal hemorrhage, gingival hyperplasia, glaucoma, glossitis, gout, gynecomastia, hematuria, hepatomegaly, herpes simplex infection, herpes zoster, hypersensitivity reaction (eg, angioedema, chest tightness, hypotension, shortness of breath, skin rash, tachycardia), hypertension, hypertonia, hypoesthesia, hypokalemia, hypotension, increased appetite, increased blood urea nitrogen, increased creatine phosphokinase, increased nonprotein nitrogen, increased serum creatinine, insomnia, jugular vein distention, keratoconjunctivitis, leukopenia, maculopapular rash, malaise, melena, migraine, myalgia, myasthenia, myocardial infarction, myositis, nocturia, oral mucosa ulcer, orthostatic hypotension, paresthesia, petechia, pleural effusion, pruritus, psoriasis (Song 2021), pustular rash, rales, retinal detachment, skin discoloration, skin photosensitivity, supraventricular tachycardia, syncope, tenosynovitis, thyroiditis, tremor, urinary frequency, urticaria, vaginal hemorrhage, venous insufficiency, ventricular premature contractions, vertigo, vision loss (temporary, unilateral), vitreous opacity, weight changes (gain/loss), wheezing (end inspiratory wheeze), xerostomia
Hypersensitivity to nisoldipine, any component of the formulation, or other dihydropyridine calcium channel blockers
Concerns related to adverse effects:
• Angina/MI: Increased angina and/or MI has occurred with initiation or dosage titration of dihydropyridine calcium channel blockers. Reflex tachycardia may occur resulting in angina and/or MI in patients with obstructive coronary disease, especially in the absence of concurrent beta-blockade.
• Hypotension/syncope: Symptomatic hypotension with or without syncope can rarely occur; blood pressure must be lowered at a rate appropriate for the patient's clinical condition. Monitor closely during initial dosing and with dosage adjustment.
• Peripheral edema: The most common side effect is peripheral edema; occurs within 2 to 3 weeks of starting therapy.
Disease-related concerns:
• Aortic stenosis: Use with caution in patients with severe aortic stenosis.
• Heart failure (HF): The ACC/AHA heart failure guidelines recommend to avoid use in patients with heart failure due to lack of benefit and/or worse outcomes with calcium channel blockers in general (ACC/AHA [Yancy 2013]).
• Hepatic impairment: Use with caution in patients with severe hepatic impairment; lower starting dose required.
• Hypertrophic cardiomyopathy and left ventricular outflow tract obstruction: Use with caution in patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition (AHA/ACC [Ommen 2020]).
Dosage form specific issues:
• Tartrazine: Some dosage forms contain tartrazine, which may cause allergic reactions in certain individuals (eg, aspirin hypersensitivity).
Special populations:
• Elderly: Use with caution in patients >65 years of age; lower starting dose recommended.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy
Atosiban: Calcium Channel Blockers may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of Calcium Channel Blockers. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy
CycloSPORINE (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of CycloSPORINE (Systemic). CycloSPORINE (Systemic) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Nisoldipine. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Nisoldipine. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Nisoldipine. Risk X: Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Nisoldipine. Risk X: Avoid combination
Dantrolene: May enhance the hyperkalemic effect of Calcium Channel Blockers. Dantrolene may enhance the negative inotropic effect of Calcium Channel Blockers. Risk X: Avoid combination
Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Grapefruit Juice: May increase the serum concentration of Nisoldipine. Risk X: Avoid combination
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Itraconazole: May increase the serum concentration of Nisoldipine. Risk X: Avoid combination
Ketoconazole (Systemic): May increase the serum concentration of Nisoldipine. Risk X: Avoid combination
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the adverse/toxic effect of Calcium Channel Blockers (Dihydropyridine). Specifically, the risk of hypotension or muscle weakness may be increased. Risk C: Monitor therapy
Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification
Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Peak concentrations of nisoldipine may be significantly increased if taken with high-lipid foods; however, total exposure (AUC) may be reduced. Grapefruit juice has been shown to significantly increase the bioavailability of nisoldipine. Management: Take on an empty stomach 1 hour before or 2 hours after a meal. Avoid a high-fat diet. Avoid grapefruit products before and after dosing.
Chronic maternal hypertension may increase the risk of birth defects, low birth weight, preterm delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to duration and severity of maternal hypertension. Untreated hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, myocardial infarction, preeclampsia, stroke, and delivery complications (ACOG 203 2019).
Calcium channel blockers may be used to treat hypertension in pregnant women; however, agents other than nisoldipine are more commonly used (ACOG 203 2019; ESC [Regitz-Zagrosek 2018]). Females with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]).
It is not known if nisoldipine is present in breast milk.
The manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother.
Take on an empty stomach (1 hour before or 2 hours after a meal). Avoid grapefruit juice before and after dosing. Avoid grapefruit juice; avoid high-fat diet.
BP, heart rate.
BP goals: May vary depending on clinical condition, different clinical practice guidelines, and expert opinion. Refer to clinical practice guidelines for specific treatment goals.
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.
Duration: >24 hours
Absorption: Well absorbed. Peak concentrations significantly increased with high-lipid meals; however, AUC is reduced.
Protein binding: >99%
Metabolism: Extensively hepatic; 1 active metabolite (10% of activity of parent); first-pass effect
Bioavailability: ~5%
Half-life elimination: 9 to 18 hours
Time to peak: 4 to 14 hours
Excretion: Urine (60% to 80% as inactive metabolites); feces
Renal function impairment: Dosage adjustments are not needed in patients with mild to moderate renal function impairment.
Hepatic function impairment: Liver cirrhosis: Increased plasma concentrations. Use lower starting and maintenance doses.
Geriatric: Higher nisoldipine plasma concentrations (Cmax and AUC) have been found in elderly patients.
Tablet, 24-hour (Nisoldipine ER Oral)
8.5 mg (per each): $6.14
17 mg (per each): $7.70
20 mg (per each): $16.45
25.5 mg (per each): $8.39
30 mg (per each): $17.94
34 mg (per each): $8.39
40 mg (per each): $17.94
Tablet, 24-hour (Sular Oral)
8.5 mg (per each): $34.80
17 mg (per each): $34.80
34 mg (per each): $34.80
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