Isradipine is a dihydropyridine calcium channel blocker (like amlodipine and nifedipine) that causes vascular smooth muscle relaxation resulting in a reduction in the blood pressure.

Isradipine Uses:

• Hypertension:

  • Isradipine is used for the management of hypertension.
  • Guideline recommendations:
    • If monotherapy is warranted, in the absence of comorbidities like cerebrovascular disease, chronic kidney disease, diabetes, heart failure, ischemic heart disease for that the guideline of 2017 for the prevention, Detection, Evaluation, and Management of High Blood pressure in adults recommend that thiazide-like diuretics or dihydropyridine calcium channel blockers may be preferred options due to improved cardiovascular endpoints (prevention of heart failure and stroke).
    • ACE inhibitors and ARBs are also recommended for monotherapy.
    • Combination therapy may be initially preferred in patients at high risk to achieve blood pressure goals (stage 2 hypertension or atherosclerotic cardiovascular disease [ASCVD] risk.

Isradipine Dose in Adults:

Isradipine Dose in the treatment of Hypertension:

• Oral: Initially 2.5 mg two times a day.
• As based on the patients' response to treatment, titrate the dose at 2-to-4 week intervals in 5 mg increments.
• The usual dose range: 5 - 10 mg per day in 2 divided doses.
• Note: Most patients show no improvement with doses exceeding 10 mg per day except for an increase in the incidence of adverse reactions; therefore, the maximum dose in older adults should not exceed 10 mg per day.

Isradipine Dose in Childrens:

Isradipine Dose in the treatment of Hypertension: Limited data available:

• Children and Adolescents: Oral:

  • Immediate-release:

    • Initial dose: 0.05 to 0.1 mg/kg/dose two to three times a day.
    • Titrate upwards at two to four-week intervals.
    • Maximum daily dose: 0.6 mg/kg/day or 10 mg/day (whichever is lower).
    • Initial doses of 0.05 to 0.15 mg/kg/dose administered three to four times a day have been suggested in patients with secondary hypertension and acute severe hypertension based on retrospective observations.
    • Usual daily dose: 0.3 to 0.4 mg/kg/day in divided doses three times a day (eg, every 8 hours).
    • Reported range: 0.04 to 1.2 mg/kg/day.
• Note: Most adult patients show no improvement with doses exceeding 10 mg per day and the incidence of adverse reactions increased.

Pregnancy Risk Factor C

• Animal reproduction studies that used doses that weren't maternally toxic did not show any adverse events.
• Isradipine passes the human placental boundary.
• Chronic maternal hypertension in the fetus, infant and mother is associated with adverse maternal and fetal events.
• Other agents may be preferred if hypertension is a concern during pregnancy.

Uuse while breastfeeding:

• • It is unknown if the drug is found in breastmilk.
  • Manufacturers recommend that you decide whether to stop breastfeeding or discontinue using the drug.
  • This is due to the possibility of serious adverse reactions in the infant.

Dose in Kidney Disease:

• The bioavailability is increased with mild renal impairment and decreased with severe renal impairment.
• However, there are no dosage adjustments provided in the manufacturer labeling.
• Other sources recommend that no initial dosage adjustment is required.
• Isradipine is not removed by hemodialysis therefore supplemental doses after hemodialysis are not necessary.

Dose in Liver disease:

There are no dosage adjustments provided in the manufacturer's labeling however peak serum concentrations are increased by 32% and bioavailability is increased by 52%.

Common Side Effects of Isradipine Include:

• Central nervous system:

  • Headache

Less Common Side Effects of Isradipine Include:

• Cardiovascular:

  • Edema
  • Flushing
  • Palpitations
  • Chest Pain
  • Tachycardia

• Central Nervous System:

  • Fatigue
  • Dizziness

• Dermatologic:

  • Skin Rash

• Gastrointestinal:

  • Nausea
  • Abdominal Distress
  • Diarrhea
  • Vomiting

• Neuromuscular & Skeletal:

  • Weakness

• Renal:

  • Urinary Frequency

• Respiratory:

  • Dyspnea

Contraindication to Isradipine Include:

• Hypersensitivity to isradipine and any component of the formulation

Warnings and precautions

• Angina and Myocardial Infarction

  • Treatment initiation or dosage adjustment of dihydropyridine calcium channels blockers has been associated with an increase in myocardial and/or angina.
  • Patients with obstructive heart disease may experience reflex tachycardia, which can lead to angina or myocardial injury. This is especially true if there is no concurrent beta-blockade.

• Hypotension/syncope

  • Rarely, symptoms of hypotension can occur with or without syncope. 
  • The patient's clinical condition dictates that blood pressure should be reduced at an appropriate rate.

• Peripheral edema

  • One common side effect of therapy is peripheral edema, which can occur within 2 to 3 days after starting treatment.

• Aortic stenosis

  • Patients with severe aortic blockage should be cautious.
  • It can lead to decreased coronary perfusion, which could result in ischemia.

• Heart failure (HF):

  • The ACC/AHA heart Failure guidelines recommend that patients suffering from heart failure should not use it.
  • This is because of the lack of benefits and/or worse outcomes than calcium channel blockers.

• Hepatic impairment

  • Patients with hepatic impairment might require a lower starting dose. Patients with hepatic impairment should be cautious.

• Hypertrophic cardiomyopathy with outflow tract obstruction (HCM)

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

Isradipine: Drug Interaction

Monitoring parameters:

• Blood pressure and heart rate

Hypertension:

The 2017 Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults Recommend:

• Confirmed hypertension and known CVD or 10-year ASCVD risk ≥10%:
  • Target blood pressure less than 130/80 mm Hg is recommended.
• Confirmed hypertension without markers of increased ASCVD risk:
  • Target blood pressure less than 130/80 mm Hg may be reasonable.

Diabetes and hypertension: The American Diabetes Association (ADA) guidelines.

• Patients 18 to 65 years of age, without ASCVD, and 10-year ASCVD risk <15%:
  • Target blood pressure less than 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 lesa than 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 less than 140/90 mm Hg is recommended.
• Patients >65 years of age (very complex/poor health):
  • Target blood pressure <less than 150/90 mm Hg is recommended.

How to administer Isradipine?

• It May be administered orally without regard to meals.

Mechanism of action of Isradipine:

• It prevents calcium ions from entering "slow channels" and select voltage-sensitive areas in vascular smooth muscles and myocardium.
• This results in relaxation of vascular soft muscle, which causes blood pressure to drop and coronary vasodilation.
• Patients with vasospastic gina experience an increase in myocardial oxygen supply

The onset of action:

• 2 to 3 hours;
• Note: Full hypotensive effect may not occur for 2 to 4 weeks.

Duration:

• more than 12 hours.

Absorption:

• 90% to 95% is absorbed when administered orally but it undergoes extensive first-pass effect.

Protein binding:

• 95%

Metabolism: It undergoes extensive first-pass effect.

• Hepatically metabolized via cytochrome P450 isoenzyme CYP3A4.
• Major metabolic pathways include oxidation and ester cleavage.
• Six inactive metabolites have been identified.

Bioavailability:

• 15% to 24%
• In patients with mild renal impairment (CrCl 30 to 80 mL/minute):
  • the bioavailability is increased by 45%; as the renal function continues to decline, this increase in AUC is reversed to a reduction in AUC as seen with severe renal impairment.
• In severe renal impairment (CrCl <10 mL/minute) and concurrent hemodialysis:
  • Decreased by 20% to 50%
• Hepatic impairment:
  • The bioavailability is increased by 52%

Half-life elimination:

• Alpha half-life: 1.5 to 2 hours;
• Terminal half-life: 8 hours

Time to peak serum concentrations:

• 1 to 1.5 hours

Excretion:

• 60% to 65% is excreted in urine as metabolites
• 25% to 30% is excreted in feces.

International Brand Names of Isradipine:

• Clivoten
• DynaCirc
• Dynacirc
• Dynacirc SR
• Dynacirc SRO
• Essadin
• Icaz LP
• Icaz SRO
• Lomir
• Lomir Retard
• Lomir SRO
• Tenzipin
• Vascal

Isradipine Brand Names in Pakistan:

No Brands Available in Pakistan.