Isradipine

Dosage Forms & Strengths

capsule

• 2.5mg
• 5mg

tablet, extended release

• 5mg
• 10mg

Hypertension

Capsule: 2.5 PO q12hr; may increase dose q2-4week at 2.5-5 mg increments to maximum 20 mg/day (most patients show no improvement with doses >10 mg/day); maximum in older adults is 10 mg/day

Controlled release tablet: 5 mg PO qDay; may increase dose by 5 mg q2-4week; not to exceed 20 mg/day (freqency of adverse effects increases with doses >10 mg/day)

Dosage Forms & Strengths

capsule

• 2.5mg
• 5mg

tablet, extended release

• 5mg
• 10mg

Hypertension (Off-label)

Capsule: 0.15-0.2 mg/kg PO qDay or divided q8-12hr, not to exceed 0.8 mg/kg/day (20 mg/day) 

Controlled release tablet: 0.15-0.2 mg/kg PO qDay or divided q12hr

Capsules: 2.5 mg PO q12hr initially

Controlled release tablet: 5 mg PO qDay initially

The bioavailabilty of isradipine is increased in the elderly population

Pregnancy Category: C

Lactation: not known if excreted into breast milk

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Mechanism of Action

Ca channel blocker: inhibits the transmembrane influx of extracellular Ca ions across the membranes of myocardial cells and vascular smooth muscle cells, without changing serum calcium concentrations, resulting in inhibition of cardiac and vascular smooth muscle contraction, thereby dilating the main coronary and systemic arteries

Pharmacokinetics

Onset: 1 hr (initial response; regular release); 2 hr (SR)

Peak response: 2-3 hr (regular release); 8-10 hr (SR)

Excretion: Urine (60-65%); feces (30%)

Peak plasma time: 1.5-3 hr (regular release); 7-18 hr (SR)

Bioavailability: 15-24%

Protein Bound: 95-97%

Vd: 3 L/kg

Metabolism: Hepatic P450 enzyme CYP3A4

Metabolites: Mono acids and a cyclic lactone product (inactive)

Clearance: 40 L/hr

Half-Life: 5-10.7 hr

Duration: 12 hr (regular release); 24 hr (SR)

Isradipine is in a group of drugs called calcium channel blockers. It works by relaxing the muscles of your heart and blood vessels.

Isradipine is used to treat high blood pressure (hypertension). It is sometimes given with other blood pressure medications.

Isradipine may also be used for purposes other than those listed in this medication guide.

You should not take this medication if you are allergic to isradipine.

Before taking isradipine, tell your doctor if you have kidney or liver disease, congestive heart failure, or a narrowing or blockage in your digestive tract.

Do not crush, chew, or break an extended-release tablet. Swallow the pill whole. Breaking the pill may cause too much of the drug to be released at one time.

Isradipine can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Some tablet forms of isradipine are made with a shell that is not absorbed or melted in the body. Therefore, you may see what looks like part of a tablet in your stool. This is a normal side effect of isradipine and will not make the medication less effective.

Keep using this medicine as directed, even if you feel well. High blood pressure often has no symptoms, so you may not know when your blood pressure is high. You may need to use blood pressure medication for the rest of your life.

To be sure this medication is helping your condition, your blood pressure will need to be checked on a regular basis. Do not miss any scheduled appointments.

Before taking isradipine, tell your doctor if you are using any of the following drugs:

• cimetidine (Tagamet, Tagamet HB);

• fentanyl (Duragesic, Ionsys, Actiq); or

• rifampin (Rifadin, Rimactane, Rifater).

This list is not complete and there may be other drugs that can interact with isradipine. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Storage

Oral

Tight, light-resistant containers at 20–25°C.82

Isradipine 1 mg/mL in simple syrup (see Reconstitution under Dosage and Administration): Stable for 35 days when refrigerated.81

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For isradipine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to isradipine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of isradipine in the pediatric population. Safety and efficacy have not been established .

Geriatric

Appropriate studies performed to date have not demonstrated geriatrics-specific problems that would limit the usefulness of isradipine in the elderly. However, elderly patients are more likely to have liver or kidney problems which may require an adjustment of dose in patients receiving isradipine .

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking isradipine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using isradipine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Mefloquine

Using isradipine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acecainide
• Acetophenazine
• Ajmaline
• Amiodarone
• Amitriptyline
• Amoxapine
• Aprindine
• Arsenic Trioxide
• Astemizole
• Azimilide
• Bretylium
• Ceritinib
• Chloral Hydrate
• Chloroquine
• Chlorpromazine
• Clarithromycin
• Clopidogrel
• Dantrolene
• Desipramine
• Dibenzepin
• Digoxin
• Disopyramide
• Dofetilide
• Dolasetron
• Doxepin
• Droperidol
• Encainide
• Enflurane
• Erythromycin
• Ethopropazine
• Flecainide
• Fluconazole
• Fluoxetine
• Fluphenazine
• Foscarnet
• Gemifloxacin
• Halofantrine
• Halothane
• Hydroquinidine
• Ibutilide
• Idelalisib
• Imipramine
• Isoflurane
• Lacosamide
• Lidoflazine
• Lorcainide
• Methotrimeprazine
• Nortriptyline
• Octreotide
• Ondansetron
• Pentamidine
• Perphenazine
• Pipotiazine
• Pirmenol
• Prajmaline
• Probucol
• Procainamide
• Prochlorperazine
• Promazine
• Promethazine
• Propafenone
• Propiomazine
• Protriptyline
• Quinidine
• Sematilide
• Sotalol
• Spiramycin
• St John's Wort
• Sulfamethoxazole
• Tedisamil
• Telithromycin
• Thiethylperazine
• Trifluoperazine
• Triflupromazine
• Trimeprazine
• Trimethoprim
• Trimipramine
• Vasopressin
• Zolmitriptan

Using isradipine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Amprenavir
• Dalfopristin
• Indinavir
• Ketoconazole
• Magnesium
• Quinupristin
• Rifampin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of isradipine. Make sure you tell your doctor if you have any other medical problems, especially:

• Bowel blockage or
• Congestive heart failure—Use with caution. May make these conditions worse .

• Kidney disease or
• Liver disease—Use with caution. The effects of isradipine may be increased because of the slower removal of the medicine from the body .

• Tell all of your health care providers that you take isradipine. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• Have your blood pressure checked often. Talk with your doctor.
• Talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
• Talk with your doctor before you drink alcohol.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using isradipine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Isradipine Capsules USP, 5 mg

Rx Only

500 Capsules

2-3 hours; Note: Full hypotensive effect may not occur for 2-4 weeks

Time to Peak

Serum: 1-1.5 hours

Hypertension (children)

Based on the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents, isradipine (among other calcium channel blockers) is an effective and recommended treatment option in pediatric patients with hypertension.

Hypersensitivity to isradipine or any component of the formulation

Refer to adult dosing.

May be taken without regard to meals.

May lead to false-negative aldosterone/renin ratio (ARR) (Funder 2016)

Blood pressure, heart rate

Adverse events were not observed in animal reproduction studies when using doses that were not maternally toxic. Isradipine crosses the human placenta (Lunell, 1993). Untreated chronic maternal hypertension is associated with adverse events in the fetus, infant, and mother. If treatment for hypertension during pregnancy is needed, other agents are preferred (ACOG, 2013).

Applies to isradipine: oral capsule, oral tablet extended release

General

Isradipine is generally well-tolerated. Most side effects occurred as commonly as with placebo in placebo-controlled trials, except for flushing, headache, and palpitations.[Ref]

Cardiovascular

Cardiovascular side effects are among the most common, and are related to the vasodilatory properties of isradipine. Peripheral edema and flushing are reported in 3% to 14% of patients, being more common at higher doses. Dizziness occurs in 3% to 8% of patients.[Ref]

Palpitations or a greater awareness of heart beats is reported in 1% to 5% of patients. Flushing and palpitations are more likely with dosages greater than 5 mg daily; women have reported flushing more than men. Edema was reported in up to 22% of patients in one study (mean dose was 5.9 mg TID). In large studies, the incidence of edema is less than 3%, and appeared to be more likely in patients greater than 60 years of age.

Isradipine does not appear to adversely affect plasma lipids.[Ref]

Nervous system

Headache was reported in up to 16% of patients in one study, although the mean dose was 5.9 mg three times daily to treat angina pectoris. Headache is more likely with dosages greater than 5 mg daily. Visual disturbances are reported in less than 2% of patients. Sleep disturbances are reported in 0.1% of patients.[Ref]

Nervous system side effects are probably related to the vasodilatory effects of isradipine. Headache is reported in 9% to 30% of patients and fatigue is reported in 7% of patients.[Ref]

Gastrointestinal

Anorexia, nausea, vomiting, and diarrhea are reported in less than 4% of patients.[Ref]

Gastrointestinal side effects are unusual, and include constipation in less than 2% of patients.[Ref]

Respiratory

Respiratory system complaints include dyspnea and cough in 2% of patients.[Ref]

Musculoskeletal

Musculoskeletal pain is reported in 1% of patients.[Ref]

Dermatologic

Dermatologic complaints of "disturbed skin sensation" are reported in less than 4% of patients.[Ref]

Hypersensitivity

Hypersensitivity reactions to isradipine are rare. Pruritus, urticaria, and angioedema have been reported.[Ref]

Some side effects of isradipine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Initial dose:
Immediate-release capsules: 2.5 mg orally twice a day
Controlled-release tablets: 5 mg orally once a day

Maintenance dose: The dose may be adjusted as needed and tolerated in increments of 5 mg at 2 to 4 week intervals.

The maximum recommended daily dose for the immediate-release capsules is 20 mg, although most patients show no additional response to doses above 10 mg/day. The maximum recommended dose for the controlled-release tablets is 20 mg/day.