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Pronunciation
(iz RA di peen)
Generic Available (U.S.)
Yes: Capsule
Brand Names: U.S.
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of hypertension
Use: Unlabeled
Pediatric hypertension
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic effects were not observed in animal studies. Israpidine crosses the human placenta. There are no adequate and well-controlled studies in pregnant women.
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Hypersensitivity to isradipine or any component of the formulation; hypotension (<90 mm Hg systolic)
Warnings/Precautions
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: The most common side effect is peripheral edema; occurs within 2-3 weeks of starting therapy.
Disease-related concerns:
• Heart failure (HF): Use with caution in patients with HF.
• Hepatic impairment: Use with caution in patients with hepatic impairment; may require lower starting dose.
• Idiopathic hypertrophic subaortic stenosis (IHSS): Use with caution in patients with IHSS.
Dosage form specific issues:
• Controlled release tablets: Use controlled release tablets with caution in patients with severe GI narrowing.
Other warnings/precautions:
• Titration: Adjust doses at 2- to 4-week intervals.
Adverse Reactions
Percentages reported with capsule formulation.
>10%: Central nervous system: Headache (dose related 2% to 22%)
1% to 10%:
Cardiovascular: Edema (dose related 1% to 9%), palpitation (dose related 1% to 5%), flushing (dose related 1% to 5%), tachycardia (1% to 3%), chest pain (2% to 3%)
Central nervous system: Dizziness (2% to 8%), fatigue (dose related 1% to 9%)
Dermatologic: Rash (2%)
Gastrointestinal: Nausea (1% to 5%), abdominal discomfort (≤3%), vomiting (≤1%), diarrhea (≤3%)
Neuromuscular & skeletal: Weakness (≤1%)
Renal: Urinary frequency (1% to 3%)
Respiratory: Dyspnea (1% to 3%)
<1%: Angioedema, atrial fibrillation, back pain, constipation, cough, cramps of legs and feet, depression, drowsiness, drug fever, dry mouth, dysuria, epistaxis, gingival hyperplasia (incidence unknown), heart failure, hyperhidrosis, hypotension, impotence, insomnia, joint pain, leg pain, lethargy, leukopenia, libido decreased, liver function tests increased, MI, nasal congestion, nervousness, nocturia, numbness, paresthesia, pruritus, stroke, syncope, throat discomfort, transient ischemic attack, urticaria, ventricular fibrillation, visual disturbance, weight gain
Metabolism/Transport Effects
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP3A4 (weak)
Drug Interactions
Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Alpha1-Blockers: May enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
Amifostine: Antihypertensives may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, antihypertensive medications should be withheld for 24 hours prior to amifostine administration. If antihypertensive therapy can not be withheld, amifostine should not be administered. Risk D: Consider therapy modification
Antifungal Agents (Azole Derivatives, Systemic): May decrease the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification
Antihypertensives: May enhance the hypotensive effect of other Antihypertensives. Risk C: Monitor therapy
ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole systemic exposure/affects with concomitant use of a weak CYP3A4 inhibitor. Decrease aripiprazole dose to 25% of the usual dose in patients receiving both a CYP3A4 and a CYP2D6 inhibitor (regardless of potencies). Risk C: Monitor therapy
Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Barbiturates: May increase the metabolism of Calcium Channel Blockers. Management: Monitor for decreased therapeutic effects of calcium channel blockers with concomitant barbiturate therapy. Calcium channel blocker dose adjustments may be necessary. Nimodipine Canadian labeling contraindicates concomitant use with phenobarbital. Risk C: Monitor therapy
Beta-Blockers: Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Beta-Blockers. Bradycardia and signs of heart failure have also been reported. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy
Calcium Channel Blockers (Nondihydropyridine): Calcium Channel Blockers (Dihydropyridine) may enhance the hypotensive effect of Calcium Channel Blockers (Nondihydropyridine). Calcium Channel Blockers (Nondihydropyridine) may increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
Calcium Salts: May diminish the therapeutic effect of Calcium Channel Blockers. Risk C: Monitor therapy
CarBAMazepine: May increase the metabolism of Calcium Channel Blockers (Dihydropyridine). Management: Consider calcium channel blocker (CCB) dose adjustments or alternative therapy in patients receiving concomitant carbamazepine. Nimodipine Canadian labeling contraindicates concurrent use with carbamazepine. Risk D: Consider therapy modification
Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of Calcium Channel Blockers. Management: Consider alternatives to cimetidine. If no suitable alternative exists, monitor for increased effects of calcium channel blockers following cimetidine initiation/dose increase, and decreased effects following cimetidine discontinuation/dose decrease. Risk D: Consider therapy modification
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ciprofloxacin (Systemic): May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Clopidogrel: Calcium Channel Blockers may diminish the therapeutic effect of Clopidogrel. Risk C: Monitor therapy
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Risk X: Avoid combination
CycloSPORINE: May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Nicardipine may likewise inhibit the metabolism of cyclosporine. Cyclosporine dosage adjustments might be needed. Risk C: Monitor therapy
CycloSPORINE (Systemic): May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates. Risk D: Consider therapy modification
Deferasirox: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Diazoxide: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
Fluconazole: May decrease the metabolism of Calcium Channel Blockers. Risk C: Monitor therapy
Fosphenytoin: Calcium Channel Blockers may increase the serum concentration of Fosphenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Risk D: Consider therapy modification
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Herbs (CYP3A4 Inducers): May increase the metabolism of CYP3A4 Substrates. Risk C: Monitor therapy
Herbs (Hypertensive Properties): May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Herbs (Hypotensive Properties): May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Hypotensive Agents: May enhance the adverse/toxic effect of other Hypotensive Agents. Risk C: Monitor therapy
Indacaterol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
Ivacaftor: May increase the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Macrolide Antibiotics: May decrease the metabolism of Calcium Channel Blockers. Management: Consider using a noninteracting macrolide. Monitor for increased therapeutic effects of calcium channel blockers if an interacting macrolide antibiotic is initiated, or decreased effects if a macrolide is discontinued. Exceptions: Azithromycin; Azithromycin (Systemic); Fidaxomicin; Spiramycin. Risk D: Consider therapy modification
Magnesium Salts: Calcium Channel Blockers may enhance the adverse/toxic effect of Magnesium Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel Blockers. Risk C: Monitor therapy
MAO Inhibitors: May enhance the hypotensive effect of Antihypertensives. MAO Inhibitors may enhance the orthostatic hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Methylphenidate: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Nafcillin: May increase the metabolism of Calcium Channel Blockers. Risk D: Consider therapy modification
Neuromuscular-Blocking Agents (Nondepolarizing): Calcium Channel Blockers may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Nitroprusside: Calcium Channel Blockers may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy
Pentoxifylline: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Phenytoin: Calcium Channel Blockers may increase the serum concentration of Phenytoin. Management: Monitor for phenytoin toxicity with concomitant use of a calcium channel blocker (CCB) or decreased phenytoin effects with CCB discontinuation. Monitor for decreased CCB therapeutic effects. Nimodipine Canadian labeling contraindicates use with phenytoin. Risk D: Consider therapy modification
Phosphodiesterase 5 Inhibitors: May enhance the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. Risk X: Avoid combination
Prostacyclin Analogues: May enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Protease Inhibitors: May decrease the metabolism of Calcium Channel Blockers (Dihydropyridine). Risk D: Consider therapy modification
QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification
QUEtiapine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
QuiNIDine: May increase the serum concentration of Calcium Channel Blockers (Dihydropyridine). Calcium Channel Blockers (Dihydropyridine) may decrease the serum concentration of QuiNIDine. Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of QuiNIDine. Risk C: Monitor therapy
QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Rifamycin Derivatives: May increase the metabolism of Calcium Channel Blockers. This primarily affects oral forms of calcium channel blockers. Management: The labeling for some U.S. and Canadian calcium channel blockers contraindicate use with rifampin however recommendations vary. Consult appropriate labeling. Risk D: Consider therapy modification
RiTUXimab: Antihypertensives may enhance the hypotensive effect of RiTUXimab. Risk D: Consider therapy modification
Tacrolimus: Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus. Risk C: Monitor therapy
Tacrolimus (Systemic): Calcium Channel Blockers (Dihydropyridine) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Toremifene: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Toremifene. The risk for potentially dangerous arrhythmias may be increased. Risk X: Avoid combination
Vandetanib: QTc-Prolonging Agents may enhance the arrhythmogenic effect of Vandetanib. Risk X: Avoid combination
Vemurafenib: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Vemurafenib. Risk X: Avoid combination
Yohimbine: May diminish the antihypertensive effect of Antihypertensives. Risk C: Monitor therapy
Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Food: Administration with food delays absorption, but does not affect availability
Herb/Nutraceutical: St John's wort may decrease isradipine levels; dong quai has estrogenic effects. Some herbal medications may worsen hypertension (eg, licorice); garlic may have additional antihypertensive effects. Management: Avoid dong quai and St John's wort. Avoid bayberry, blue cohosh, cayenne, ephedra, ginger, ginseng (American), gotu kola, licorice, yohimbe, and garlic.
Mechanism of Action
Inhibits calcium ion from entering the “slow channels” or select voltage-sensitive areas of vascular smooth muscle and myocardium during depolarization, producing a relaxation of coronary vascular smooth muscle and coronary vasodilation; increases myocardial oxygen delivery in patients with vasospastic angina
Pharmacodynamics/Kinetics
Onset of action: Immediate release: 2-3 hours
Duration: Immediate release: >12 hours
Absorption: 90% to 95%
Distribution: Vd: 3 L/kg
Protein binding: 95%
Metabolism: Hepatic; CYP3A4 substrate (major); extensive first-pass effect; forms metabolites (inactive)
Bioavailability: 15% to 24%
Half-life elimination: Terminal: 8 hours
Time to peak, serum: 1-1.5 hours
Excretion: Urine (60% to 65% as metabolites); feces (25% to 30%)
Dosage
Oral:
Children (unlabeled use): Capsule: Initial: 0.15-0.2 mg/kg/day in 2-3 divided doses; maximum 0.8 mg/kg/day, up to 20 mg/day. Note: Controlled release formulation is administered once daily or in 2 divided doses.
Adults:
Capsule: 2.5 mg twice daily; antihypertensive response occurs in 2-3 hours; maximal response in 2-4 weeks; increase dose at 2- to 4-week intervals at 2.5-5 mg increments; usual dose range (JNC 7): 2.5-10 mg/day in 2 divided doses. Note: Most patients show no improvement with doses >10 mg/day except adverse reaction rate increases; therefore, maximal dose in older adults should be 10 mg/day.
Controlled release tablet: 5 mg once daily; antihypertensive response occurs in 2 hours. Adjust dose in increments of 5 mg at 2-4 week intervals. Maximum dose: 20 mg/day; adverse events are increased at doses >10 mg/day.
Elderly:
Capsule: Refer to adult dosing.
Controlled release tablet: Initial dose: 5 mg once daily
Dosage adjustment in renal impairment: Clcr 30-80 mL/minute: Bioavailability increased by 45%. Clcr <10 mL/minute on hemodialysis: Bioavailability decreased by 20% to 50%
Capsule: Refer to adult dosing.
Controlled release tablet: Initial dose: 5 mg once daily
Dosage adjustment in hepatic impairment: Peak serum concentrations are increased by 32% and bioavailability is increased by 52%
Capsule: Refer to adult dosing.
Controlled release tablet: Initial dose: 5 mg once daily
Administration: Oral
May be administered without regard to meals. Controlled release tablets should be swallowed whole; do not divide or chew
Monitoring Parameters
Blood pressure; renal, hepatic dysfunction
Dietary Considerations
May be taken without regard to meals.
Patient Education
Take with or without food. Do not crush extended release tablets. Follow prescriber's instructions for diet and lifestyle changes. You may experience headache, constipation, dizziness, or ankle swelling. Report unrelieved headache, severe constipation, chest pain, palpitations, swelling of feet or weight gain, or chest pain or pressure.
Geriatric Considerations
Elderly may experience a greater hypotensive response. Constipation may be more of a problem in the elderly. Calcium channel blockers are no more effective in the elderly than other therapies; however, they do not cause significant CNS effects which is an advantage over some antihypertensive agents.
Cardiovascular Considerations
Isradipine alone or in combination with other agents is effective in the management of hypertension.
In the treatment of unstable angina/non-ST-segment elevation MI, a nondihydropyridine calcium antagonist (diltiazem or verapamil) may be considered in patients with continuing or frequently recurring ischemia when beta-blockers are contraindicated (Class I). Oral long-acting calcium antagonists may also be considered in addition to beta-blockers and nitrates (Class IIa).
Dental Health: Effects on Dental Treatment
Unlike other calcium channel blockers, information is sparse as to whether isradipine causes gingival hyperplasia. Consultation with physician is suggested if hyperplasia is observed in patients taking isradipine.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Isradipine is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, mepivacaine and levonordefrin [Carbocaine® 2% with Neo-Cobefrin®]) be used with caution.
Dental Comment
Isradipine is known to prolong the QT interval. The QT interval is measured as the time and distance between the Q point of the QRS complex and the end of the T wave in the ECG tracing. After adjustment for heart rate, the QT interval is defined as prolonged if it is more than 450 msec in men and 460 msec in women. A long QT syndrome was first described in the 1950s and 60s as a congenital syndrome involving QT interval prolongation and syncope and sudden death. Some of the congenital long QT syndromes were characterized by a peculiar electrocardiographic appearance of the QRS complex involving a premature atria beat followed by a pause, then a subsequent sinus beat showing marked QT prolongation and deformity. This type of cardiac arrhythmia was originally termed “torsade de pointes” (translated from the French as “twisting of the points”). Isradipine is considered as having a risk of causing torsade de pointes. Since it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval, a medical consult is suggested.
Mental Health: Effects on Mental Status
May cause dizziness or drowsiness
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Monitor for tachycardia, hypotension, edema, and dyspnea at regular intervals during therapy. When discontinuing, taper dose slowly.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, oral: 2.5 mg, 5 mg
Tablet, controlled release, oral:
DynaCirc CR®: 5 mg, 10 mg
Pricing: U.S. (www.drugstore.com)
Capsules (Isradipine)
2.5 mg (60): $75.99
Tablet, 24-hour (DynaCirc CR)
5 mg (30): $83.99
10 mg (30): $129.99
Extemporaneously Prepared
A 1 mg/mL oral suspension may be made from isradipine capsules; glycerin, USP; and Simple Syrup, N.F. Empty the contents of ten 5 mg isradipine capsules into a glass mortar. Add a small portion of glycerin, USP and mix to a fine paste; mix while adding 15 mL of simple syrup and transfer contents to a 60 mL amber glass prescription bottle. Rinse mortar with 10 mL simple syrup, NF and transfer to the prescription bottle; repeat, and add quantity of vehicle sufficient to make 50 mL. Label "protect from light", "refrigerate", and "shake well". Stable for 35 days when stored in amber glass prescription bottles in the dark and refrigerated.
MacDonald JL, Johnson CE, and Jacobson P, “Stability of Isradipine in Extemporaneously Compounded Oral Liquids,” Am J Hosp Pharm, 1994, 51(19):2409-11.
References
Braunwald E, Antman EM, Beasley JW, et al, “ACC/AHA Guidelines for the Management of Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina),” J Am Coll Cardiol, 2000, 36(3):970-1062.
Chobanian AV, Bakris GL, Black HR, et al, “The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,” JAMA, 2003, 289(19):2560-71.
Lunell NO, Bondesson U, Grunewald C, et al, “Transplacental Passage of Isradipine in the Treatment of Pregnancy-Induced Hypertension,” Am J Hypertens, 1993, 6(3 Pt 2):110-11.
National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents, “The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents,” Pediatrics, 2004, 114(2 Suppl):555-76.
Steele RM, Schuna AA, and Schreiber RT, “Calcium Antagonist-Induced Gingival Hyperplasia,” Ann Intern Med, 1994, 120(8):663-4.
International Brand Names
Lexi-Comp.com
Last full review/revision March 2012
Content last modified March 2012
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