Nisoldipine

Nisoldipine is an antihypertensive belonging to Calcium channel blocker.

Nisoldipine is a calcium channel blocker used as monotherapy or combined with other drugs for the treatment of hypertension.

Bioavailability of Nisoldipine is about 4-8%. Peak Plasma Time and Duration of action of Nisoldipine is approximately 6-12 hours and 24 hours respectively. Nisoldipine is about 99% of protein binding. The volume of distribution of Nisoldipine is approximately 4-5 L/kg. Undergoes rapid and extensive first-pass metabolism in the gut wall and liver by CYP3A4. The metabolites, Hydroxylated isobutyl ester derivative (active, 10% potency of parent drug). The elimination half-life of Nisoldipine is Approximately 7-12 hours. The drug is mainly excreted via urine (approx 60-80%) and feces (remaining dose as metabolites).

Nisoldipine shows common side effects like Headache, Peripheral edema, Dizziness, Palpitation, Vasodilation, Increased severity of angina, Nausea, Pharyngitis, Sinusitis, etc.

Nisoldipine is available in the form of Oral Tablets.

Nisoldipine is available in India, US, UK, Canada, China, and Italy.

Nisoldipine belonging to the Calcium Channel Blocker, acts as an antihypertensive agent.

Nisoldipine inhibits the influx of extracellular calcium across the myocardial and vascular smooth muscle cell membranes. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.

The Onset of action of Nisoldipine not clinically established.

The Duration of Action for Nisoldipine in the body is approximately 24 hours.

The Tmax was found within 4-14 hours following the administration of Nisoldipine.

Nisoldipine is available in the form of Oral Tablets.

Nisoldipine Tablet is taken orally, usually once a day.

Nisoldipine is a calcium channel blocker used as monotherapy or combined with other drugs for the treatment of hypertension.

Nisoldipine is an antihypertensive agent belonging to calcium channel blocker.

Nisoldipine is a dihydropyridine Calcium channel blocker. It inhibits the movement of Calcium ions into vascular smooth muscle and cardiac muscle. It reversibly competes with other dihydropyridines for binding to the Calcium channel.

Nisoldipine is approved for use in the following clinical indications

● Hypertension

Nisoldipine is indicated for the treatment of hypertension. It may be used alone or in combination with other antihypertensive agents.

● Hypertension

Slow release (old / original formulation)

Initial dose: 20 mg orally once a day.

Maintenance dose: 10 to 60 mg orally once a day.

Maximum dose: 60 mg/day.

Controlled release (New formulation / Geomatrix delivery system)

Initial dose: 17 mg orally once a day.

Maintenance dose: 8.5 to 34 mg orally once a day.

Maximum dose: 34 mg/day.Nisoldipine is available in various strengths as 8.5mg, 17mg, 20mg, 25.5mg, 30mg and 34mg.

Nisoldipine is available in various strengths as 8.5mg, 17mg, 20mg, 25.5mg, 30mg and 34mg.

Nisoldipine is available in the form of Oral Tablets.

Dosage Adjustment in Kidney Patient

Mild to moderate impairment: No dosage adjustment necessary.

Severe impairment: No dosage adjustment provided.

Dosage Adjustment in Hepatic impairment Patient

Nisoldipine Controlled release (New formulation / Geomatrix delivery system)

Oral: Initial dose should not exceed 8.5 mg once daily.

Nisoldipine extended release (old / original formulation)

Oral: Initial dose should not exceed 10 mg once daily.

● Avoid taking Nisoldipine with high-fat foods or high-fat meals.

● Avoid drinking grapefruit juice or eating grapefruit while taking Nisoldipine.

Nisoldipine is contraindicated in patients with

● Nisoldipine is contraindicated in patients with known hypersensitivity to dihydropyridine calcium channel blockers

● 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.

● 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.

● 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

● Tartrazine:

Some dosage forms contain tartrazine, which may cause allergic reactions in certain individuals (eg, aspirin hypersensitivity).

Information is not available.

It is not known whether Nisoldipine is excreted in human milk. Because many drugs are excreted in human milk, a decision should be made to discontinue nursing, or to discontinue Nisoldipine, taking into account the importance of the drug to the mother.

Pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

● Avoid taking Nisoldipine with high-fat foods or high-fat meals.

● Avoid drinking grapefruit juice or eating grapefruit while taking Nisoldipine.

Common Adverse effects

● Headache, Peripheral edema, Dizziness, Palpitation, Vasodilation, Increased severity of angina, Nausea, Pharyngitis, Sinusitis.

Rare Adverse effects

● Gingival hyperplasia, Colitis, Anemia, Alopecia, Anorexia, Anxiety, Ischemia, Diabetes mellitus, Dyspepsia, Dysphagia, Dysuria, hematuria, impotence, nocturia, urinary frequency, increased BUN and serum creatinine, vaginal hemorrhage, vaginitis.

● Alpha1-Blockers: Coadministration may enhance the hypotensive effect of Calcium Channel Blockers.

● 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.

● Antipsychotic Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation).

● 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.

● Barbiturates: Coadministration may enhance the hypotensive effect of Blood Pressure Lowering Agents.

● Benperidol: Coadministration may enhance the hypotensive effect of Blood Pressure Lowering Agents.

● Brigatinib: Coadministration may diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents.

● Calcium Salts: Coadministration may diminish the therapeutic effect of Calcium Channel Blockers.

● Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel.

● 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).

● CYP3A4 Inducers (Moderate): Coadministration may decrease the serum concentration of Nisoldipine.

● CYP3A4 Inducers (Strong): Coadministration may decrease the serum concentration of Nisoldipine.

● Dantrolene: May enhance the hyperkalemic effect of Calcium Channel Blockers. Dantrolene may enhance the negative inotropic effect of Calcium Channel Blockers.

● Fusidic Acid (Systemic): Coadministration may increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).

● Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents.

● Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products.

● Magnesium Sulphate: Coadministration may enhance the adverse/toxic effect of Calcium Channel Blockers (Dihydropyridine). Specifically, the risk of hypotension or muscle weakness may be increased.

● Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine).

● Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing).

● 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.

● Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents.

● Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents.

● 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.

● Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic).

The common side effects of Nisoldipine include the following

Common

● Swelling, headache, dizziness; or flushing, headache, upset stomach, dizziness or light-headedness, flushing, fast heartbeat, excessive tiredness, nasal congestion, sore throat.

Rare

● light-headed feeling, chest pain or pressure, pain spreading to your jaw or shoulder, swelling in your hands or feet, flushing (sudden warmth, redness, or tingly feeling), fast heartbeats; or sudden numbness or weakness, problems with vision or speech.

● Pregnancy

Pregnancy Category C

Nisoldipine was neither teratogenic nor fetotoxic at doses that were not maternally toxic. Nisoldipine was fetotoxic but not teratogenic in rats and rabbits at doses resulting in maternal toxicity (reduced maternal body weight gain). In pregnant rats, increased fetal resorption (post implantation loss) was observed at 100 mg/kg/day and decreased fetal weight was observed at both 30 and 100 mg/kg/day. These doses are, respectively, about 5 and 16 times the MRHD when compared on a mg/m2 basis. In pregnant rabbits, decreased fetal and placental weights were observed at a dose of 30 mg/kg/day, about 10 times the MRHD when compared on a mg/m2 basis. In a study in which pregnant monkeys (both treated and control) had high rates of abortion and mortality, the only surviving fetus from a group exposed to a maternal dose of 100 mg Nisoldipine /kg/day (about 30 times the MRHD when compared on a mg/m2 basis) presented with forelimb and vertebral abnormalities not previously seen in control monkeys of the same strain. There are no adequate and well controlled studies in pregnant women. Nisoldipine should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

● Nursing Mothers

It is not known whether Nisoldipine is excreted in human milk. Because many drugs are excreted in human milk, a decision should be made to discontinue nursing, or to discontinue Nisoldipine, taking into account the importance of the drug to the mother.

● Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

● Geriatric Use

Clinical studies of Nisoldipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Patients over 65 are expected to develop higher plasma concentrations of Nisoldipine. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy.

There is no experience with Nisoldipine overdosage. Generally, overdosage with other dihydropyridines leading to pronounced hypotension calls for active cardiovascular support including monitoring of cardiovascular and respiratory function, elevation of extremities, judicious use of calcium infusion, pressor agents and fluids. Clearance of Nisoldipine would be expected to be slowed in patients with impaired liver function. Since Nisoldipine is highly protein bound, dialysis is not likely to be of any benefit; however, plasmapheresis may be beneficial.

● Pharmacodynamic

Nisoldipine, a dihydropyridine calcium-channel blocker, is used alone or with an angiotensin-converting enzyme inhibitor, to treat hypertension, chronic stable angina pectoris, and Prinzmetals variant angina. Nisoldipine is similar to other peripheral vasodilators. Nisoldipine inhibits the influx of extra cellular calcium across the myocardial and vascular smooth muscle cell membranes possibly by deforming the channel, inhibiting ion-control gating mechanisms, and/or interfering with the release of calcium from the sarcoplasmic reticulum. The decrease in intracellular calcium inhibits the contractile processes of the myocardial smooth muscle cells, causing dilation of the coronary and systemic arteries, increased oxygen delivery to the myocardial tissue, decreased total peripheral resistance, decreased systemic blood pressure, and decreased afterload.

● Pharmacokinetics

Absorption

Bioavailability of Nisoldipine is about 4-8%. Peak Plasma Time and Duration of action of Nisoldipine is approximately 6-12 hours and 24 hours respectively.

Distribution

Nisoldipine is about 99% of protein binding. The volume of distribution of Nisoldipine is approximately 4-5 L/kg.

Metabolism and Excretion

Undergoes rapid and extensive first-pass metabolism in the gut wall and liver by CYP3A4. The metabolites, Hydroxylated isobutyl ester derivative (active, 10% potency of parent drug). The elimination half-life of Nisoldipine is Approximately 7-12 hours. The drug is mainly excreted via urine (approx 60-80%) and feces (remaining dose as metabolites).

https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020356s027lbl.pdf

https://www.rxlist.com/sular-drug.htm

https://reference.medscape.com/drug/sular-nisoldipine-342379

https://go.drugbank.com/drugs/DB00401

https://www.drugs.com/mtm/nisoldipine.html#:~:text=What is nisoldipine?,listed in this medication guide.

https://www.mims.com/philippines/drug/info/nisoldipine?mtype=generic