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Hypertension: Management of hypertension, alone or in combination with other antihypertensive agents
The 2014 guideline for the management of high blood pressure in adults (JNC 8) recommends initiation of pharmacologic treatment to lower blood pressure for the following patients (JNC 8 [James, 2013]):
- Patients ≥60 years of age with systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg. Goal of therapy is SBP <150 mm Hg and DBP <90 mm Hg.
- Patients <60 years of age with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
- Patients ≥18 years of age with diabetes with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
- Patients ≥18 years of age with chronic kidney disease (CKD) with SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.
In patients with chronic kidney disease (CKD), regardless of race or diabetes status, the use of an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) as initial therapy is recommended to improve kidney outcomes. In the general nonblack population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic, calcium channel blocker, ACEI, or ARB. In the general black population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic or a calcium channel blocker instead of an ACEI or ARB.
Hypersensitivity to nisoldipine, any component of the formulation, or other dihydropyridine calcium channel blockers
Hypertension: Oral:
Sular (Geomatrix delivery system): Oral: Initial: 17 mg once daily, then increase by 8.5 mg/week (or longer intervals) to attain adequate control of blood pressure
Usual dose range: 17-34 mg once daily; doses >34 mg once daily are not recommended
Nisoldipine extended-release tablet (original formulation): Initial: 20 mg once daily, then increase by 10 mg/week (or longer intervals) to attain adequate control of blood pressure
Usual dose range: 20-40 mg once daily; doses >60 mg once daily are not recommended
Conversion from nisoldipine extended-release (original formulation) to Sular Geomatrix delivery system:
Nisoldipine Extended Release Dosing EquivalencyOriginal Extended Release 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
Table has been converted to the following text.
Nisoldipine Extended Release Dosing Equivalency
Original extended release formulation dose 10 mg equals
Sular Geomatrix dose 8.5 mg
Original extended release formulation dose 20 mg equals
Sular Geomatrix dose 17 mg
Original extended release formulation dose 30 mg equals
Sular Geomatrix dose 25.5 mg
Original extended release formulation dose 40 mg equals
Sular Geomatrix dose 34 mg
Hypertension: Oral:
Sular (Geomatrix delivery system): Initial dose: 8.5 mg once daily; increase by 8.5 mg/week (or longer intervals) to attain adequate blood pressure control
Nisoldipine extended-release (original formulation): Initial dose: 10 mg once daily; increase by 10 mg/week (or longer intervals) to attain adequate blood pressure control.
Conversion from nisoldipine extended-release (original formulation) to Sular Geomatrix delivery system: Refer to adult dosing.
Mild to moderate impairment: No dosage adjustment necessary .
Severe impairment: No dosage adjustment provided in manufacturers labeling.
Sular (Geomatrix delivery system): An initial dose exceeding 8.5 mg once daily is not recommended for patients with hepatic impairment.
Nisoldipine extended-release (original formulation): An initial dose exceeding 10 mg once daily is not recommended for patients with hepatic impairment.
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.
Take on an empty stomach (1 hour before or 2 hours after a meal). Avoid grapefruit juice before and after dosing. Avoid grapefuit juice; avoid high-fat diet.
Store at controlled room temperature of 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F). Protect from light; protect from moisture.
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
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy
Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. Consider therapy modification
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Monitor therapy
Aprepitant: May increase the serum concentration of CYP3A4 Substrates. 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. Monitor therapy
Barbiturates: May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Monitor therapy
Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Monitor therapy
Cimetidine: May increase the serum concentration of Calcium Channel Blockers. Management: Consider alternatives to cimetidine. If no suitable alternative exists, monitor for increased effects of calcium channel blockers following cimetidine initiation/dose increase, and decreased effects following cimetidine discontinuation/dose decrease. Consider therapy modification
Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
CycloSPORINE (Systemic): May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Nisoldipine. Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Nisoldipine. Avoid combination
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Nisoldipine. Avoid combination
Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Monitor therapy
Dasatinib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Monitor therapy
Fluconazole: May increase the serum concentration of Calcium Channel Blockers. Monitor therapy
Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Grapefruit Juice: May increase the serum concentration of Nisoldipine. Avoid combination
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Monitor therapy
Idelalisib: May increase the serum concentration of CYP3A4 Substrates. Avoid combination
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Levodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa. Monitor therapy
Luliconazole: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Felodipine Canadian labeling specifically recommends avoiding its use in combination with clarithromycin. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Consider therapy modification
Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Monitor therapy
Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Netupitant: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. 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. Consider therapy modification
Osimertinib: May increase the serum concentration of CYP3A4 Substrates. Osimertinib may decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Palbociclib: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy
Siltuximab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Simeprevir: May increase the serum concentration of CYP3A4 Substrates. Monitor therapy
Stiripentol: May increase the serum concentration of CYP3A4 Substrates. Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification
Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use cannot be avoided, initiate tizanidine at an adult dose of 2 mg and increase in 2-4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Monitor therapy
Yohimbine: May diminish the antihypertensive effect of Antihypertensive Agents. Monitor therapy
Blood pressure, heart rate
>10%:
Cardiovascular: Peripheral edema (dose related; 7% to 29%)
Central nervous system: Headache (22%)
1% to 10%:
Cardiovascular: Vasodilation (4%), palpitation (3%), angina exacerbation (2%), chest pain (2%)
Central nervous system: Dizziness (3% to 10%)
Dermatologic: Rash (2%)
Gastrointestinal: Nausea (2%)
Respiratory: Pharyngitis (5%), sinusitis (3%)
<1% (Limited to important or life-threatening): Alopecia, amblyopia, amnesia, anemia, anorexia, anxiety, appetite increased, arthralgia, arthritis, asthma, ataxia, atrial fibrillation, blepharitis, BUN increased, bruising, cellulitis, cerebral ischemia, colitis, conjunctivitis, creatinine increased, creatine kinase increased, CVA, depression, diabetes mellitus, diaphoresis, diarrhea, dreams abnormal, dyspepsia, dysphagia, dyspnea, dysuria, end inspiratory wheeze, epistaxis, exfoliative dermatitis, facial edema, fever, first-degree AV block, flu-like syndrome, gastritis, gastrointestinal hemorrhage, gingival hyperplasia, glaucoma, glossitis, gout, gynecomastia, heart failure (decompensated), hematuria, hepatomegaly, herpes simplex, herpes zoster; hypersensitivity reaction (eg, angioedema, shortness of breath, tachycardia, chest tightness, hypotension, and rash); hyper-/hypotension, hypertonia, hypoesthesia, hypokalemia, insomnia, jugular venous distention, keratoconjunctivitis, leukopenia, libido decreased, liver function tests abnormal, maculopapular rash, malaise, melena, migraine, mouth ulceration, myalgia, myasthenia, MI, myositis, nocturia, nonprotein nitrogen increased, orthostatic hypotension, paresthesia, petechiae, photosensitivity, pleural effusion, pruritus, pustular rash, rales, retinal detachment, skin discoloration, skin ulcer, somnolence, supraventricular tachycardia, syncope, systolic ejection murmur, taste disturbance, temporary unilateral loss of vision, tenosynovitis, thyroiditis, tremor; T-wave abnormalities on ECG (flattening, inversion, nonspecific changes); urinary frequency, urticaria, vaginal hemorrhage, venous insufficiency, ventricular extrasystoles, vertigo, vitreous floater, weight gain/loss, xerostomia
Dosage adjustments are not needed in patients with mild to moderate renal function impairment.
Liver cirrhosis: Increased plasma concentrations. Use lower starting and maintenance doses.
Higher nisoldipine plasma concentrations (Cmax and AUC) have been found in elderly.
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 patients clinical condition. Monitor closely during initial dosing and with dosage adjustment.
- Peripheral edema: The most common side effect is peripheral edema; occurs within 2-3 weeks of starting therapy.
Disease-related concerns:
- Aortic stenosis: Use with caution in patients with severe aortic stenosis.
- Heart failure (HF): The ACCF/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 (Yancy, 2013]).
- Hepatic impairment: Use with caution in patients with severe hepatic impairment; lower starting dose required.
- Hypertrophic cardiomyopathy (HCM) with outflow tract obstruction: Use with caution in patients with HCM and outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition.
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.
C
Adverse events were not observed in animal reproduction studies when using doses that were not maternally toxic. Untreated chronic maternal hypertension is associated with adverse events in the fetus, infant, and mother. If treatment for hypertension during pregnancy is needed, other agents are preferred (ACOG, 2013).
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.
Well absorbed. Peak concentrations significantly increased with high-lipid meals; however, AUC is reduced.
Extensively hepatic; 1 active metabolite (10% of activity of parent); first-pass effect
Urine (60% to 80% as inactive metabolites); feces
4-14 hours
>24 hours
9-18 hours
>99%
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience pharyngitis or headache. Have patient report immediately to prescriber severe dizziness, passing out, shortness of breath, excessive weight gain, swelling of arms or legs, or angina (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.