Nisoldipine - Uses, Dosage, Side effects, Contraindications

Nisoldipine is a dihydropyridine calcium channel blocker that relaxes the vascular smooth muscles. It is used in the management of hypertension.

Nisoldipine Uses:

  • Hypertension:

    • Used for management of hypertension

Guideline recommendations:

  • In the absence of comorbidities (such as cerebrovascular disease, chronic kidney disease, diabetes, heart failure, ischemic heart disease, etc.), the 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults suggests that thiazide-like diuretics or dihydropyridine calcium channel blockers may be preferable options due to improved cardiovascular endpoints (eg, prevention of heart failure and stroke).
  • ARBs and ACE inhibitors are also suitable for monotherapy.
  • Combination therapy is first favoured in individuals with high risk conditions (stage 2 hypertension or atherosclerotic cardiovascular disease), where it may be necessary to meet blood pressure targets.

Nisoldipine Dose in Adults

Nisoldipine Dose in the treatment of Hypertension: Oral:

  • Sular (Geomatrix delivery system):

    • Oral: Initial: 17 mg once a day, then increase by 8.5 mg/week (or longer intervals) to attain adequate control of blood pressure
    • Usual dose range: 17 to 34 mg once a day; doses >34 mg once a day are not recommended
  • Nisoldipine extended-release tablet (original formulation):

    • Initial:20 mg once daily; titrate weekly as necessary by 10 mg/week based on patient response (or longer intervals)
    • The usual dosage range is 20 to 40 mg once daily; doses greater than 60 mg once daily are not advised.

Conversion from nisoldipine extended-release (original formulation) to Sular Geomatrix delivery system:

Nisoldipine Extended-Release Dosing Equivalency

Original Extended-Release FormulationSular Extended-Release (Geomatrix delivery system)
10 mg 8.5 mg
20 mg 17 mg
30 mg 25.5 mg
40 mg 34 mg

Use in Children:

Not indicated

Pregnancy Risk Factor C

  • Animal reproduction studies that used doses that weren't maternally toxic did not show any adverse events.
  • Chronic maternal hypertension, if not treated, can lead to adverse outcomes in the infant, mother, and fetus.
  • Other agents may be preferred if hypertension is a concern during pregnancy.

Nisoldipine use during breastfeeding:

  • Nisoldipine may secrete in breast milk, however this is uncertain.
  • Manufacturers advise consumers to decide whether to cease breastfeeding or stop taking the medication.
  • Taking into account the significance of the mother's care, this should be done.

Nisoldipine Dose in Kidney Disease:

Mild to moderate impairment:

  • No dosage change is required.

Severe impairment:

  • The manufacturer's labelling makes no mention of adjusting the dosage.

Nisoldipine Dose in Liver disease:

  • Sular (Geomatrix delivery system):

    • For patients with hepatic impairment, a starting dose more than 8.5 mg given once daily is not advised.
  • Nisoldipine extended-release (original formulation):

    • For patients with hepatic impairment, an initial dose more than 10 mg given once daily is not advised.

Common Side Effects of Nisoldipine:

  • Cardiovascular:

    • Peripheral Edema
  • Central Nervous System:

    • Headache

Less Common Side Effects Of Nisoldipine:

  • Cardiovascular:

    • Vasodilation
    • Palpitations
    • Exacerbation Of Angina Pectoris
    • Chest Pain
  • Central Nervous System:

    • Dizziness
  • Dermatologic:

    • Skin Rash
  • Gastrointestinal:

    • Nausea
  • Respiratory:

    • Pharyngitis
    • Sinusitis

Contraindications to Nisoldipine:

  • Hypersensitivity to nisoldipine, any ingredient in the formulation, or other calcium channel blockers that include the dihydropyridine ring

Warnings and precautions

  • Angina/MI

    • There have been reports that the use of or dosage titration for dihydropyridine calcium channel blockers causes an increase in angina and/or MI.
    • Patients with obstructive heart disease may experience reflex tachycardia, which can lead to angina or MI. This is especially true if there is no concurrent beta-blockade.
  • Hypotension/syncope

    • Syncope can occasionally occur along with or without hypotension symptoms.
    • The rate of blood pressure reduction must be suitable for the patient's medical condition.
    • Ensure that you are attentive during dosage adjustments and initial dosing.
  • Peripheral edema

    • The most frequent adverse effect is peripheral edoema. Usually, it happens 2 to 3 weeks after therapy begins.
  • Aortic stenosis

    • Patients with severe aortic blockage should be cautious.
  • Heart failure (HF):

    • According to the ACC/AHA guidelines for heart failure, patients with heart disease should not use calcium channel blockers.
    • This is because they are likely to have worse outcomes and/or no benefit.
  • Hepatic impairment

    • Patients with severe liver disease should exercise caution.
    • A lower starting dose required.
  • Hypertrophic cardiomyopathy with outflow tract obstruction (HCM)

    • Patients who have HCM or an obstruction of the outflow tract should exercise caution because a decrease in afterload can make their symptoms worse.

Nisoldipine: Drug Interaction

Note: Drug Interaction Categories:

  • Risk Factor C: Monitor When Using Combination
  • Risk Factor D: Consider Treatment Modification
  • Risk Factor X: Avoid Concomitant Use

Risk Factor C (Monitor therapy)

Alfuzosin The hypotensive effects of blood pressure-lowering medications may be strengthened.
Alpha1-Blockers The hypotensive effects of calcium channel blockers may be strengthened.
Amphetamines May lessen the effectiveness of antihypertensive agents.
Antipsychotic Agents (Second Generation [Atypical]) Antipsychotic drugs' hypotensive effects may be enhanced by blood pressure-lowering medications (Second Generation [Atypical]).
Aprepitant May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Atosiban Calcium channel blockers may intensify Atosiban's harmful or hazardous effects. Particularly, pulmonary edoema and/or dyspnea may be at higher risk.
Barbiturates Calcium Channel Blockers' metabolic rate might be increased. Management: Keep an eye out for any diminished therapeutic effects of barbiturate medication when concurrently using calcium channel blockers. There may need to be dose modifications with calcium channel blockers. The concurrent use of phenobarbital and nimodipine is not recommended.
Barbiturates The hypotensive effects of blood pressure-lowering medications may be strengthened.
Benperidol The hypotensive effects of blood pressure-lowering medications may be strengthened.
Brigatinib May lessen the effectiveness of antihypertensive agents. Antihypertensive Agents' bradycardic action may be strengthened by brutinib.
Brimonidine (Topical) The hypotensive effects of blood pressure-lowering medications may be strengthened.
Calcium Channel Blockers (Nondihydropyridine) Dihydropyridine, a calcium channel blocker, may increase the hypotensive effects of calcium channel blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may cause an increase in serum calcium channel blocker concentration (Dihydropyridine).
Calcium Salts May reduce calcium channel blockers' therapeutic efficacy.
Clofazimine May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Clopidogrel Calcium channel blockers may reduce Clopidogrel's therapeutic efficacy.
CycloSPORINE (Systemic) The serum concentration of CycloSPORINE may rise when Calcium Channel Blockers (Dihydropyridine) are taken (Systemic). Calcium Channel Blockers' serum levels may rise when CycloSPORINE (Systemic) is used (Dihydropyridine).
CYP3A4 Inhibitors (Moderate) May increase the serum levels of CYP3A4 substrates (High risk with Inhibitors).
Dapoxetine May intensify calcium channel blockers' orthostatic hypotensive effects.
Deferasirox May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Dexmethylphenidate Can lessen an antihypertensive drug's therapeutic impact.
Diazoxide Blood pressure-lowering medicines may strengthen their hypotensive effects.
DULoxetine The hypotensive impact of DULoxetine may be enhanced by blood pressure lowering medications.
Duvelisib May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Erdafitinib May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Erdafitinib May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Fluconazole Calcium Channel Blockers' serum levels can rise.
Fosaprepitant May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Fosnetupitant May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Herbs (Hypertensive Properties) .May reduce the effectiveness of antihypertensive agents
Herbs (Hypotensive Properties) Blood pressure-lowering medicines may strengthen their hypotensive effects.
Hypotension-Associated Agents The hypotensive action of hypotension-associated agents may be strengthened by blood pressure lowering medications
Ivosidenib May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Larotrectinib May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Levodopa-Containing Products Levodopa-Containing Products' hypotensive effects may be strengthened by blood pressure-lowering medications.
Lormetazepam The hypotensive effects of blood pressure-lowering medications may be strengthened.
Magnesium Salts Calcium channel blockers might make magnesium salts more harmful or poisonous. Calcium Channel Blockers' hypotensive effects may be strengthened by magnesium salts.
Melatonin May reduce the effectiveness of calcium channel blockers as an antihypertensive (Dihydropyridine).
Methylphenidate May lessen the effectiveness of antihypertensive agents.
Molsidomine The hypotensive effects of blood pressure-lowering medications may be strengthened.
Naftopidil The hypotensive effects of blood pressure-lowering medications may be strengthened.
Netupitant May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Neuromuscular-Blocking Agents (Nondepolarizing) The neuromuscular-blocking impact of neuromuscular-blocking agents may be enhanced by calcium channel blockers (Nondepolarizing).
Nicergoline The hypotensive effects of blood pressure-lowering medications may be strengthened.
Nicorandil The hypotensive effects of blood pressure-lowering medications may be strengthened.
Nitroprusside Nitroprusside's hypotensive impact may be strengthened by blood pressure-lowering medications.
Palbociclib May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Pentoxifylline The hypotensive effects of blood pressure-lowering medications may be strengthened.
Pholcodine Pholcodine's hypotensive impact may be strengthened by blood pressure lowering medications.
Phosphodiesterase 5 Inhibitors The hypotensive effects of blood pressure-lowering medications may be strengthened.
Prostacyclin Analogues The hypotensive effects of blood pressure-lowering medications may be strengthened.
Quinagolide The hypotensive effects of blood pressure-lowering medications may be strengthened.
Sarilumab May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Siltuximab May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Simeprevir May elevate the serum level of CYP3A4 substrates (High risk with Inducers).
Tacrolimus (Systemic) Tacrolimus serum levels may rise when Calcium Channel Blockers (Dihydropyridine) are used (Systemic).
Tocilizumab May lower the serum level of CYP3A4 substrates (High risk with Inducers).
Yohimbine May lessen the effectiveness of antihypertensive agents.

Risk Factor D (Consider therapy modification)

Amifostine Amifostine's hypotensive impact may be strengthened by blood pressure lowering medications. Treatment: Blood pressure-lowering drugs need to be avoided for 24 hours before amifostine is administered when used at chemotherapeutic doses. Amifostine should not be given if blood pressure lowering treatment cannot be stopped.
Cimetidine Calcium Channel Blockers' serum levels can rise. Management: Take cimetidine substitutes into consideration. If there is no suitable substitute, watch for increased calcium channel blocker effects after starting or increasing the dosage of cimetidine and decreased effects after stopping or decreasing the dosage.
Macrolide Antibiotics Calcium Channel Blockers' metabolic rate might be decreased. Use a noninteracting macrolide as a possible management strategy. The Canadian labelling for felodipine expressly advises against using it in conjunction with clarithromycin. Azithromycin (Systemic), Fidaxomicin, Roxithromycin, and Spiramycin are exceptions.
Obinutuzumab The hypotensive effects of blood pressure-lowering medications may be strengthened. Management: Take into account temporarily stopping blood pressure-lowering drugs 12 hours before the start of the obinutuzumab infusion and keeping them off until 1 hour after the infusion is finished.
Sincalide The therapeutic benefit of Sincalide may be reduced by medications that affect gallbladder function. Prior to using sincalide to induce gallbladder contraction, you should think about stopping any medications that can impair gallbladder motility.
Stiripentol May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors). Management: Due to the increased potential for side effects and toxicity, stiripentol should not be used with CYP3A4 substrates that are thought to have a narrow therapeutic index. Use of stiripentol with any CYP3A4 substrate necessitates closer observation.

Risk Factor X (Avoid combination)

Bromperidol The hypotensive impact of bromperidol may be enhanced by blood pressure lowering medications. Blood Pressure Lowering Agents' hypotensive effects may be lessened by bromperidol.
Conivaptan May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
CYP3A4 Inducers (Moderate) Nisoldipine's serum concentration can drop.
CYP3A4 Inducers (Strong) Nisoldipine's serum concentration can drop.
CYP3A4 Inhibitors (Strong) Nisoldipine's serum concentration can drop.
Fusidic Acid (Systemic) May elevate CYP3A4 substrates' serum concentration (High risk with Inhibitors).
Grapefruit Juice Nisoldipine's serum concentration can drop.
Idelalisib Nisoldipine's serum concentration can drop.

Monitoring parameters:

Blood pressure and heart rate

Hypertension:

  • The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (ACC/AHA [Whelton 2017]):

Confirmed hypertension and known CVD or 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10%:

  • Target blood pressure <130/80 mm Hg is recommended

Confirmed hypertension without markers of increased ASCVD risk:

  • Target blood pressure <130/80 mm Hg may be reasonable

Diabetes and hypertension:

  • The American Diabetes Association (ADA) guidelines (ADA 2019):
  • Patients 18 to 65 years of age, without ASCVD, and 10-year ASCVD risk <15%: Target blood pressure <140/90 mm Hg is recommended
  • Patients 18 to 65 years of age and known ASCVD or 10-year ASCVD risk >15%: Target blood pressure <130/80 mm Hg may be appropriate if it can be safely attained
  • Patients >65 years of age (healthy or complex/intermediate health): Target blood pressure <140/90 mm Hg is recommended
  • Patients >65 years of age (very complex/poor health): Target blood pressure <150/90 mm Hg is recommended

How to administer Nisoldipine?

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.

Mechanism of action of Nisoldipine:

  • Nisoldipine is a dihydropyridine calcium-channel blocker that is structurally similar to nifedipine. It prevents calcium ions from moving into cardiac and vascular smooth muscles.
  • Dihydropyridines can be potent vasodilators, but they are less likely to slow cardiac conduction and suppress cardiac contractility than other calcium antagonists like verapamil or diltiazem.
  • Nisoldipine has a 5-10x greater vasodilator potency than 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:

  • 9-18 hours

Time to peak:

  • 4-14 hours

Excretion:

  • Urine (60% to 80% as inactive metabolites); feces

International Brands of Nisoldipine:

  • Sular
  • Angiolat
  • Baymycard
  • Bo Ping
  • Corasol
  • Ke Di
  • Mo Tai
  • Nisodipen
  • Nisoldin
  • Sular
  • Syscor
  • Syscor CC
  • Syscor MR

Nisoldipine Brand Names in Pakistan:

No Brands Available in Pakistan.