Isradipine is a medication primarily used to treat high blood pressure (hypertension). It belongs to a class of drugs known as calcium channel blockers. Isradipine works by relaxing and widening blood vessels, making it easier for blood to flow. This helps to lower blood pressure and reduce the workload on the heart. It's typically taken orally in the form of tablets.
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:
- Start with 2.5 milligrams (mg) twice a day.
- Your doctor may increase the dose every 2 to 4 weeks, depending on how you respond, by adding 5 mg at a time.
- The typical range is 5 to 10 mg per day, split into two doses.
Note: It's important to note that for most people, doses higher than 10 mg per day don't provide extra benefits but can increase the chances of side effects. So, the highest recommended dose for older adults is 10 mg per day.
Isradipine Dose in Children:
Isradipine Dose in the treatment of Hypertension: Limited data available:
For children and adolescents with limited data available:
- Start with 0.05 to 0.1 milligrams (mg) per kilogram (kg) of body weight, given 2 to 3 times a day.
- Your doctor may increase this dose every 2 to 4 weeks.
- The maximum daily dose shouldn't exceed 0.6 mg/kg/day or 10 mg/day (whichever is lower).
In certain cases, like secondary hypertension or acute severe hypertension, initial doses of 0.05 to 0.15 mg/kg/dose given 3 to 4 times daily have been suggested. The usual daily dose in these cases is 0.3 to 0.4 mg/kg/day split into doses every 8 hours.
Remember, just like in adults, doses higher than 10 mg per day in children and adolescents may not provide additional benefits and could increase the risk of side effects.
Pregnancy Risk Factor C
- Isradipine carries a pregnancy risk factor of C, meaning its safety during pregnancy hasn't been well studied.
- Animal studies didn't show harm to the fetus at non-toxic doses, but Isradipine does pass through the placenta in humans.
- Chronic high blood pressure in pregnant women can lead to problems for both the mother and the baby.
- If hypertension treatment is necessary during pregnancy, other medications are usually preferred for safety reasons, according to the American College of Obstetricians and Gynecologists.
Uuse while breastfeeding:
- It's unclear if Isradipine passes into breast milk.
- Because there's a risk of serious side effects in breastfed babies, the manufacturer suggests considering whether to stop breastfeeding or stop taking the medication, weighing the importance of treatment for the mother.
Isradipine Dose in Kidney Disease:
- The manufacturer doesn't specify dosage adjustments in their labeling, but it's noted that Isradipine's effectiveness can change with kidney function.
- Mild kidney impairment can increase its availability in the body, while severe impairment can decrease it.
- However, according to Aronoff in 2007, no initial dosage adjustment is typically needed.
- Additionally, Isradipine isn't removed by hemodialysis, so extra doses after the procedure aren't required, as stated by Schönholzer in 1992.
Isradipine Dose in Liver disease:
- The manufacturer's label doesn't include dosage adjustments based on this information.
- However, it's noted that peak serum concentrations increase by 32% and bioavailability 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:
- If someone has a hypersensitivity, or severe allergic reaction, to Isradipine or any ingredient in the medication, they shouldn't take it.
Warnings and precautions
Angina and Myocardial Infarction
- Starting or increasing the dose of dihydropyridine calcium channel blockers, like Isradipine, can sometimes lead to increased angina (chest pain) or myocardial infarction (heart attack).
- This risk is higher in patients with obstructive coronary disease.
- Additionally, reflex tachycardia (rapid heart rate) might occur, potentially worsening angina or heart attack, especially if beta-blockers are not being used alongside.
- It's essential for patients with these conditions to be closely monitored when starting or adjusting their medication regimen.
Hypotension/syncope
- Occasionally, symptomatic hypotension (low blood pressure) may develop, potentially leading to fainting (syncope).
- It's crucial to lower blood pressure gradually, tailored to the individual's clinical status, to avoid this.
- Monitoring blood pressure regularly and adjusting medication doses as needed can help prevent these adverse effects.
Peripheral edema
- Peripheral edema, swelling in the legs or ankles, is a common side effect of Isradipine and tends to be related to the dose.
- It might start appearing about 2 to 3 weeks after starting the medication.
Aortic stenosis
- Extreme caution is advised when using Isradipine in patients with severe aortic stenosis, a condition where the heart's aortic valve narrows.
- This caution is because Isradipine may reduce coronary perfusion, potentially leading to inadequate blood flow to the heart muscle, known as ischemia.
- Patients with severe aortic stenosis should be closely monitored when using Isradipine, and alternative treatment options might be considered in some cases.
Heart failure (HF):
- According to the American College of Cardiology/American Heart Association (ACC/AHA) guidelines on heart failure, it's recommended to avoid using Isradipine or other calcium channel blockers in patients with heart failure.
- This recommendation is based on findings that calcium channel blockers may not provide benefits and could potentially lead to worse outcomes in patients with heart failure.
Hepatic impairment
- In patients with hepatic (liver) impairment, using Isradipine requires caution.
- It might be necessary to start with a lower dose than usual.
- This approach helps to minimize the risk of adverse effects and ensures the medication is appropriately metabolized by the liver.
Hypertrophic cardiomyopathy with outflow tract obstruction (HCM)
- In patients with hypertrophic cardiomyopathy (HCM) and outflow tract obstruction, caution is advised when using Isradipine.
- This is because reducing the afterload (the force the heart needs to pump against) may worsen symptoms associated with this condition.
Isradipine: Drug Interaction
|
Risk Factor C (Monitor therapy) |
|
|
Alpha1-Blockers |
The hypotensive effects of calcium channel blockers may be strengthened. |
|
Alfuzosin |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Antipsychotic Agents (Second Generation [Atypical]) |
Antipsychotic drugs' hypotensive effects may be enhanced by blood pressure-lowering medications (Second Generation [Atypical]). |
|
Aprepitant |
may increase CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
|
Amphetamines |
may lessen the effectiveness of antihypertensive agents. |
|
Atosiban |
Calcium channel blockers may intensify Atosiban's harmful or hazardous effects. Particularly, pulmonary edoema and/or dyspnea may be at higher risk. |
|
Barbiturates |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Bosentan |
may lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
Brigatinib |
may lessen the effectiveness of antihypertensive agents. Antihypertensive Agents' bradycardic action may be strengthened by Brigatinib. |
|
Brimonidine (Topical) |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Calcium Channel Blockers (Nondihydropyridine) |
Calcium Channel Blockers may have an enhanced hypotensive impact when used with dihydropyridine (Nondihydropyridine). Nondihydropyridine, a calcium channel blocker, may cause a rise in the serum level of calcium channel blockers (Dihydropyridine). |
|
Calcium Salts |
may lessen calcium channel blockers' ability to treat illness. |
|
Clopidogrel |
The therapeutic benefit of clopidogrel may be reduced by calcium channel blockers. |
|
CYP3A4 Inhibitors (Moderate) |
may slow down CYP3A4 substrate metabolism (High risk with Inhibitors). |
|
Dapoxetine |
may intensify calcium channel blockers' orthostatic hypotensive effects. |
|
Deferasirox |
may lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
Dexmethylphenidate |
can lessen an antihypertensive drug's therapeutic impact. |
|
Diazoxide |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Efavirenz |
May lower the level of calcium channel blockers in the serum. |
|
Magnesium Salts |
Calcium channel blockers could make magnesium salts more harmful or poisonous. Calcium Channel Blockers' hypotensive effects may be strengthened by magnesium salts. |
|
Erdafitinib |
may lower the level of CYP3A4 substrates in the serum (High risk with Inducers). |
|
Levodopa-Containing Products |
Levodopa-Containing Products' hypotensive effects may be strengthened by blood pressure-lowering medications. |
|
Erdafitinib |
may raise the serum level of CYP3A4 substrates (High risk with Inhibitors). |
|
Herbs (Hypertensive Properties) |
reduce the effectiveness of antihypertensive agents in treating hypertension. |
|
Fosaprepitant |
may raise the serum level of CYP3A4 substrates (High risk with Inhibitors). |
|
Ivosidenib |
may lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
Fosnetupitant |
may raise the serum level of CYP3A4 substrates (High risk with Inhibitors). |
|
DULoxetine |
The hypotensive impact of DULoxetine may be enhanced by blood pressure lowering medications. |
|
Fluconazole |
The serum level of calcium channel blockers may rise. |
|
Duvelisib |
may increase CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
|
CycloSPORINE (Systemic) |
Calcium Channel Blockers (Dihydropyridine) may raise CycloSPORINE serum concentration (Systemic). The blood concentration of Calcium Channel Blockers may rise when CycloSPORINE (Systemic) is used (Dihydropyridine). |
|
Herbs (Hypotensive Properties) |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Larotrectinib |
may increase CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
|
Barbiturates |
Calcium Channel Blockers' metabolic rate could be increased. Management: Keep an eye out for any diminished therapeutic benefits of barbiturate medication when concurrently using calcium channel blockers. There may need to be dosage modifications with calcium channel blockers. The concurrent use of phenobarbital and nimodipine is not recommended. |
|
Hypotension-Associated Agents |
The hypotensive action of hypotension-associated agents may be strengthened by blood pressure lowering medications. |
|
Lormetazepam |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Methylphenidate |
may lessen the effectiveness of antihypertensive agents. |
|
Molsidomine |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
CYP3A4 Inducers (Moderate) |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). |
|
Netupitant |
may increase CYP3A4 substrates' serum concentration (High risk with Inhibitors). |
|
Melatonin |
may reduce the effectiveness of calcium channel blockers as an antihypertensive (Dihydropyridine). |
|
Neuromuscular-Blocking Agents (Nondepolarizing) |
The neuromuscular-blocking impact of neuromuscular-blocking agents may be enhanced by calcium channel blockers (Nondepolarizing). |
|
Naftopidil |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Nicergoline |
BP lowering medications may have an enhanced hypotensive impact. |
|
Nitroprusside |
Nitroprusside's hypotensive impact may be strengthened by blood pressure-lowering medications. |
|
Nicorandil |
BP lowering medications may have an enhanced hypotensive impact. |
|
Palbociclib |
May elevate serum levels of CYP3A4 substrates (High risk with Inhibitors). |
|
Benperidol |
The hypotensive effects of blood pressure-lowering medications may be strengthened. |
|
Pholcodine |
Pholcodine's hypotensive impact may be strengthened by blood pressure lowering medications. |
|
Pentoxifylline |
BP lowering medications may have an enhanced hypotensive impact. |
|
Prostacyclin Analogues |
BP lowering medications may have an enhanced hypotensive impact. |
|
Quinagolide |
BP lowering medications may have an enhanced hypotensive impact. |
|
Phosphodiesterase 5 Inhibitors |
BP lowering medications may have an enhanced hypotensive impact. |
|
Sarilumab |
may lower the level of CYP3A4 substrates in the serum (High risk with Inducers). |
|
Siltuximab |
may lower the level of CYP3A4 substrates in the serum (High risk with Inducers). |
|
QuiNIDine |
QuiNIDine's serum levels may be decreased by calcium channel blockers (Dihydropyridine). QuiNIDine's serum levels may rise when calcium channel blockers (Dihydropyridine) are used. The blood level of Calcium Channel Blockers may rise when quinine is taken (Dihydropyridine). |
|
Tacrolimus (Systemic) |
Tacrolimus serum levels could be elevated by calcium channel blockers (Dihydropyridine) (Systemic). |
|
Tocilizumab |
may lower the level of CYP3A4 substrates in the serum (High risk with Inducers). |
|
Clofazimine |
may raise the serum level of CYP3A4 substrates (High risk with Inhibitors). |
|
Simeprevir |
may raise the serum level of CYP3A4 substrates (High risk with Inhibitors). |
|
Yohimbine |
reduce the effectiveness of antihypertensive agents in treating hypertension. |
|
Risk Factor D (Consider therapy modification) |
|
|
Antifungal Agents (Azole Derivatives, Systemic) |
Calcium Channel Blockers' harmful or toxic effects might be exacerbated. In particular, itraconazole may make verapamil or diltiazem's unfavourable inotropic effects worse. Calcium Channel Blockers' metabolism may be slowed down by antifungal agents (systemic azole derivatives). Fluconazole and isavuconazonium, which are covered in different monographs, probably have less powerful effects than those of other azoles. Treatment: Itraconazole should not be used concurrently with felodipine or nisoldipine. With any such combination, regular monitoring is advised; calcium channel blocker dose decreases could be necessary. Fluconazole and isavuconazonium sulphate are exceptions. |
|
Amifostine |
Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When amifostine is used at chemotherapy doses, blood pressure lowering medications should be withheld for 24 hours prior to amifostine administration. If blood pressure lowering therapy cannot be withheld, amifostine should not be administered. |
|
Cimetidine |
Calcium Channel Blockers' serum levels can rise. Management: Take cimetidine substitutes into consideration. If there is no acceptable substitute, watch for increased calcium channel blocker effects after starting or increasing the dosage of cimetidine and decreased effects after stopping or decreasing the dosage. |
|
CYP3A4 Inhibitors (Strong) |
May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). |
|
CarBAMazepine |
Calcium Channel Blockers' metabolism might be accelerated (Dihydropyridine). In individuals taking concurrent carbamazepine, consider adjusting the dosage of calcium channel blockers (CCBs) or switching to an alternative form of treatment. The Canadian labelling for nimodipine expressly forbids using it alongside carbamazepine. |
|
Enzalutamide |
May lower the serum level of CYP3A4 substrates (High risk with Inducers). Treatment: Enzalutamide should not be used concurrently with CYP3A4 substrates that have a limited therapeutic index. Enzalutamide use, like with the use of any other CYP3A4 substrate, should be done cautiously and under close observation. |
|
CYP3A4 Inducers (Strong) |
may speed up CYP3A4 substrate metabolism (High risk with Inducers). Management: Take into account a substitute for one of the interfering medications. Specific contraindications may apply to some combinations. the relevant manufacturer's label. |
|
Lorlatinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. |
|
Dabrafenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). |
|
Macrolide Antibiotics |
Calcium Channel Blockers' metabolic rate could be decreased. Use a noninteracting macrolide as a possible management strategy. The Canadian labelling for felodipine expressly advises against using it in conjunction with clarithromycin. Exceptions: Fidaxomicin, Roxithromycin, Spiramycin, and systemic azithromycin. |
|
Fosphenytoin |
Calcium channel blockers may raise the level of fosphenytoin in the blood. Monitoring for phenytoin toxicity while using a calcium channel blocker (CCB) at the same time or reduced phenytoin effects while stopping the CCB are the two management options. Check for diminished therapeutic effects of CCB. The Canadian labelling for nimodipine specifically forbids the use of phenytoin. |
|
MiFEPRIStone |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. |
|
Obinutuzumab |
The hypotensive effects of blood pressure-lowering medications may be strengthened. Management: Take into account temporarily stopping blood pressure-lowering drugs 12 hours before the start of the obinutuzumab infusion and keeping them off until 1 hour after the infusion is finished. |
|
Mitotane |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. |
|
Phenytoin |
The blood levels of phenytoin may rise when calcium channel blockers are used. Calcium Channel Blockers' serum levels may be reduced by phenytoin. Avoid combining nimodipine or nifedipine with phenytoin for management. With any concurrent usage, keep an eye out for phenytoin toxicity and/or diminished calcium channel blocker effects. |
|
Rifamycin Derivatives |
Calcium Channel Blockers' serum concentration can drop. This predominantly affects calcium channel blockers used orally. Management: Using rifampin with certain calcium channel blockers is not advised according to the labelling in the US and Canada. Look up the relevant labels. |
|
Stiripentol |
may increase CYP3A4 substrates' serum concentration (High risk with Inhibitors). Management: Due to the increased potential for side effects and toxicity, stiripentol should not be used with CYP3A4 substrates that are thought to have a narrow therapeutic index. The use of stiripentol with any CYP3A4 substrate necessitates cautious observation. |
|
Sincalide |
The therapeutic benefit of Sincalide may be reduced by medications that affect gallbladder function. Prior to using sincalide to induce gallbladder contraction, you should think about stopping any medications that can impair gallbladder motility. |
|
Risk Factor X (Avoid combination) |
|
|
Conivaptan |
CYP3A4 Substrates' serum levels may rise (High risk with Inhibitors). |
|
Bromperidol |
Agents that lower blood pressure may make bromperidol's hypotensive impact stronger. Blood Pressure Lowering Agents may have less of a hypotensive impact when used with bromperidol. |
|
Idelalisib |
CYP3A4 Substrates' serum levels may rise (High risk with Inhibitors). |
|
Fusidic Acid (Systemic) |
CYP3A4 Substrates' serum levels may rise (High risk with Inhibitors). |
Monitoring parameters:
Blood Pressure
Hypertension:
- For Patients with Confirmed Hypertension and Known Cardiovascular Disease (CVD) or 10-Year ASCVD Risk ≥10%:
- Target blood pressure: <130/80 mm Hg is recommended (ACC/AHA [Whelton 2017]).
- For Patients with Confirmed Hypertension Without Markers of Increased ASCVD Risk:
- Target blood pressure: <130/80 mm Hg may be reasonable (ACC/AHA [Whelton 2017]).
Diabetes and Hypertension:
- For Patients 18 to 65 Years Without ASCVD, and 10-Year ASCVD Risk <15%:
- Target blood pressure: <140/90 mm Hg is recommended (ADA 2019).
- For Patients 18 to 65 Years with Known ASCVD or 10-Year ASCVD Risk >15%:
- Target blood pressure: <130/80 mm Hg may be appropriate if it can be safely attained (ADA 2019).
- For Patients >65 Years of Age (Healthy or Complex/Intermediate Health):
- Target blood pressure: <140/90 mm Hg is recommended (ADA 2019).
- For Patients >65 Years of Age (Very Complex/Poor Health):
- Target blood pressure: <150/90 mm Hg is recommended (ADA 2019).
How to administer Isradipine?
- Oral Administration:
- Isradipine can be taken without regard to meals.
Mechanism of action of Isradipine:
- Isradipine works by blocking calcium ions from entering specific areas in the walls of blood vessels and heart muscle when they're stimulated, which happens during heartbeats.
- This blocking action relaxes the muscles in blood vessels, leading to widened coronary arteries and lower blood pressure.
- This widening also boosts the delivery of oxygen to the heart muscle, which is helpful for patients with vasospastic angina, a condition where blood flow to the heart is temporarily restricted due to spasms in the coronary arteries.
Onset of Action:
- Begins within 2 to 3 hours. Note: Full hypotensive effect may take 2 to 4 weeks to occur.
Duration:
- Lasts more than 12 hours.
Absorption
- Absorption Rate:
- 90% to 95%, but subject to a significant first-pass effect.
Distribution
- Volume of Distribution (V):
- 3 liters per kilogram (L/kg).
- Protein Binding:
- High, at 95%.
Metabolism
- Metabolism Pathway:
- Primarily hepatic metabolism via cytochrome P450 isoenzyme CYP3A4.
- Major Metabolic Pathways:
- Include oxidation and ester cleavage, leading to six inactive metabolites.
Bioavailability
- Percentage Absorbed:
- Ranges from 15% to 24%.
- Impact of Renal Impairment:
- Mild renal impairment (CrCl 30 to 80 mL/minute) increases bioavailability by 45%, but this effect reverses with severe impairment.
- Impact of Hepatic Impairment:
- Increases bioavailability by 52%.
Elimination
- Half-life:
- Alpha half-life: 1.5 to 2 hours; Terminal half-life: 8 hours.
- Time to Peak Serum Concentration:
- 1 to 1.5 hours after administration.
- Excretion:
- Primarily through urine (60% to 65% as metabolites) and feces (25% to 30%).
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.
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