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:

• The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults recommends if monotherapy is warranted, in the absence of comorbidities (eg, cerebrovascular disease, chronic kidney disease, diabetes, heart failure, ischemic heart disease, etc), that thiazide-like diuretics or dihydropyridine calcium channel blockers may be preferred options due to improved cardiovascular endpoints (eg, prevention of heart failure and stroke).
• ACE inhibitors and ARBs are also acceptable for monotherapy.
• Combination therapy may be required to achieve blood pressure goals and is initially preferred in patients at high risk (stage 2 hypertension or atherosclerotic cardiovascular disease.

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 a day; titrate weekly as needed based on patient response by 10 mg/week (or longer intervals)
  • Usual dosage range: 20 to 40 mg once a day; doses >60 mg once a day are not recommended

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

Nisoldipine Extended-Release Dosing Equivalency

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:

• It is unknown if nisoldipine secretes in breast milk.
• Manufacturers recommend that a decision is made about whether to stop breastfeeding or discontinue using the drug.
• This should be done taking into consideration the importance of the mother's treatment.

Nisoldipine Dose in Kidney Disease:

Mild to moderate impairment:

• No dosage adjustment is necessary.

Severe impairment:

• No dosage adjustment provided in the manufacturer's labeling.

Nisoldipine Dose in Liver disease:

• Sular (Geomatrix delivery system):

  • An initial dose exceeding 8.5 mg once a day is not recommended for patients with hepatic impairment.

• Nisoldipine extended-release (original formulation):

  • An initial dose exceeding 10 mg once a day is not recommended for patients with hepatic impairment.

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 component of the formulation, or other dihydropyridine calcium channel blockers

Warnings and precautions

• Angina/MI

  • Angina and/or MI have been reported to increase with the initiation of or dosage titration for dihydropyridine calcium channels blockers.
  • 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

  • Rarely, symptoms of hypotension can be experienced with or without syncope.
  • Blood pressure must be reduced at a pace that is appropriate for the patient's medical condition.
  • Ensure that you are attentive during dosage adjustments and initial dosing.

• Peripheral edema

  • Peripheral edema is the most common side effect. It usually occurs within 2 to 3-weeks of starting therapy.

• 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 hepatic impairment should be cautious
  • A lower starting dose required.

• Hypertrophic cardiomyopathy with outflow tract obstruction (HCM)

  • Patients with HCM or outflow tract obstruction should be cautious as a reduction in afterload could worsen the symptoms.

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

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.