Hypertension: Oral: Initial: 2.5 mg twice daily; titrate at 2- to 4-week intervals as needed based on patient response in 5 mg increments; usual dose range: 5 to 10 mg/day in 2 divided doses (ACC/AHA [Whelton 2017]). Note: Most patients show no improvement with doses >10 mg daily except adverse reaction rate increases; therefore, maximal dose in older adults should be 10 mg daily.
There are no dosage adjustments provided in manufacturer's labeling; however, bioavailability is increased with mild renal impairment and decreased with severe renal impairment. Other sources recommend that no initial dosage adjustment is required (Aronoff 2007). Isradipine is not removed by hemodialysis; therefore, supplemental doses after hemodialysis are not necessary (Schönholzer 1992).
There are no dosage adjustments provided in manufacturer's labeling; however, peak serum concentrations are increased by 32% and bioavailability is increased by 52%.
(For additional information see "Isradipine: Pediatric drug information")
Hypertension: Limited data available: Children and Adolescents: Oral: Immediate release: Initial: 0.05 to 0.1 mg/kg/dose 2 to 3 times daily; titrate upwards at 2- to 4-week intervals; maximum daily dose: 0.6 mg/kg/day or 10 mg/day (whichever is lower) (AAP [Flynn 2017]). Based on retrospective observations, initial doses of 0.05 to 0.15 mg/kg/dose administered 3 to 4 times daily have been suggested in patients with secondary hypertension and acute severe hypertension; usual daily dose: 0.3 to 0.4 mg/kg/day in divided doses (eg, every 8 hours); reported range: 0.04 to 1.2 mg/kg/day (Flynn 2002; Flynn 2009; Johnson 1997; Miyashita 2010; Strauser 2000). Note: Most adult patients show no improvement with doses >10 mg daily and adverse reaction rate increases.
There are no dosage adjustments provided in manufacturer's labeling; however, bioavailability is increased with mild renal impairment; trend is reversed with further renal function deterioration. Other sources recommend that no initial dosage adjustment is required in pediatric and adult patients (Aronoff 2007). Isradipine is not removed by hemodialysis; therefore, supplemental doses after hemodialysis are not necessary (Schönholzer 1992).
There are no dosage adjustments provided in manufacturer's labeling; however, adult pharmacokinetic data has shown peak serum concentrations are increased by 32% and bioavailability is increased by 52%; use with caution.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Generic: 2.5 mg, 5 mg
Yes
Oral: May be administered without regard to meals.
Oral: May be administered without regard to meals.
Hypertension: 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), that thiazide-like diuretics or dihydropyridine calcium channel blockers may be preferred options due to improved cardiovascular end points (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 [ASCVD] risk ≥10%) (ACC/AHA [Whelton 2017]).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Central nervous system: Headache (dose related 2% to 22%)
1% to 10%:
Cardiovascular: Edema (dose related 1% to 9%), flushing (dose related 1% to 5%), palpitations (dose related 1% to 5%), chest pain (3%), tachycardia (1% to 3%)
Central nervous system: Fatigue (dose related ≤9%), dizziness (2% to 8%)
Dermatologic: Skin rash (2%)
Gastrointestinal: Nausea (3% to 5%), abdominal distress (≤3%), diarrhea (≤3%), vomiting (≤1%)
Neuromuscular & skeletal: Weakness (≤1%)
Renal: Urinary frequency (1% to 3%)
Respiratory: Dyspnea (3%)
<1%, postmarketing, and/or case reports: Atrial fibrillation, cardiac failure, cerebrovascular accident, constipation, cough, decreased libido, depression, drowsiness, foot cramps, hyperhidrosis, hypotension, impotence, increased liver enzymes, insomnia, leg cramps, lethargy, leukopenia, myocardial infarction, nervousness, nocturia, numbness, paresthesia, pruritus, psoriasis (Song 2021), sore throat, syncope, transient ischemic attacks, urticaria, ventricular fibrillation, visual disturbance, xerostomia
Hypersensitivity to isradipine or any component of the formulation
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 patient's clinical condition.
• Peripheral edema: A common side effect is peripheral edema (dose-dependent); may begin within 2 to 3 weeks of starting therapy.
Disease-related concerns:
• Aortic stenosis: Use with extreme caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia.
• 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 (ACC/AHA [Yancy 2013]).
• Hepatic impairment: Use with caution in patients with hepatic impairment; may require lower starting dose.
• 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.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: 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. Risk C: Monitor therapy
Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination
Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of Calcium Channel Blockers. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy
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). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Isradipine. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Isradipine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Isradipine. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Isradipine. Risk C: Monitor therapy
Dantrolene: May enhance the hyperkalemic effect of Calcium Channel Blockers. Dantrolene may enhance the negative inotropic effect of Calcium Channel Blockers. Risk X: Avoid combination
Dapoxetine: May enhance the orthostatic hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fosphenytoin-Phenytoin: Isradipine may increase the serum concentration of Fosphenytoin-Phenytoin. Fosphenytoin-Phenytoin may decrease the serum concentration of Isradipine. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Risk C: Monitor therapy
Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the adverse/toxic effect of Calcium Channel Blockers (Dihydropyridine). Specifically, the risk of hypotension or muscle weakness may be increased. Risk C: Monitor therapy
Melatonin: May diminish the antihypertensive effect of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy
Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: 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. Risk D: Consider therapy modification
Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy
Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Administration with food delays absorption, but does not affect availability. Management: Administer without regard to meals.
Isradipine crosses the human placenta. In a study of 16 women, umbilical cord concentrations were less than maternal serum (Lunell 1993).
Chronic maternal hypertension may increase the risk of birth defects, low birth weight, preterm delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to duration and severity of maternal hypertension. Untreated hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, myocardial infarction, preeclampsia, stroke, and delivery complications (ACOG 203 2019).
Calcium channel blockers may be used to treat hypertension in pregnant women; however, agents other than isradipine are more commonly used (ACOG 203 2019; ESC [Regitz-Zagrosek 2018]). Females with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]).
It is not known if isradipine is present in breast milk.
Due to the potential for serious adverse reactions in the breastfeeding infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother.
BP, heart rate.
BP goals: May vary depending on clinical condition, different clinical practice guidelines, and expert opinion. Refer to clinical practice guidelines for specific treatment goals.
Inhibits calcium ion from entering the “slow channels” or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization, producing relaxation of vascular smooth muscle, resulting in coronary vasodilation and reduced blood pressure; increases myocardial oxygen delivery in patients with vasospastic angina
Onset of action: 2 to 3 hours; Note: Full hypotensive effect may not occur for 2 to 4 weeks
Duration: >12 hours
Absorption: 90% to 95%, but large first-pass effect
Distribution: Vd: 3 L/kg
Protein binding: 95%
Metabolism: 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%
Mild renal impairment (CrCl 30 to 80 mL/minute): Increased by 45%; as renal function continues to decline, this increase in AUC is reversed to a reduction in AUC as seen with severe renal impairment.
Severe renal impairment (CrCl <10 mL/minute); concurrent hemodialysis: Decreased by 20% to 50%
Hepatic impairment: Increased by 52%
Half-life elimination: Alpha half-life: 1.5 to 2 hours; Terminal half-life: 8 hours
Time to peak, serum: 1 to 1.5 hours
Excretion: Urine (60% to 65% as metabolites); feces (25% to 30%)
Hepatic function impairment: The Cmax increases by 32%
Geriatric: The AUC and Cmax increases.
Capsules (Isradipine Oral)
2.5 mg (per each): $1.90 - $12.20
5 mg (per each): $2.78 - $12.34
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