Drug Class Description
Calcium-channel blockers (class II calcium antagonists).

Generic Name
Isradipine

Drug Description
One tablet contains 2.5mg isradipine INN

Presentation
Yellow circular flat bevelled edge, angle scored tablets, 6mm in diameter, marked NM on one side and CIBA on the other

Indications
PRESCAL is recommended for the treatment of essential hypertension

Adult Dosage
Route of administration: oralPRESCAL can be administered with or without food.The recommended dosage is 2.5 mg twice a day (i.e. about every 12 hours). Treatment for 3-4 weeks is required for the maximum effect to develop. If blood pressure is not adequately controlled after this period patients may require a dosage of 5 mg twice a day, or if more appropriate, the addition of a low dose of another anti-hypertensive agent i.e. thiazide diuretic, ACE inhibitor or beta-blocker. Exceptionally some patients may require up to 10mg twice a day. PRESCAL can also be added to an ongoing regimen of other anti-hypertensive agents.When PRESCAL is given concurrently with cimetidine, the dosage of PRESCAL should be reduced by 50%.

Child Dosage
The efficacy and safety of PRESCAL has not been established in children and is therefore not recommended in these patients.

Elderly Dosage
Use in the elderly and in patients with impaired hepatic or renal function:In elderly patients or in patients where hepatic or renal function is impaired, a more suitable starting dose is 1.25 mg (1/2 tablet) twice a day for hypertension. However, the dosage may be increased according to the requirements of the individual patient. Once daily maintenance treatment with 2.5 mg or 5 mg may be sufficient in some hypertensive patients.

Contra Indications
Patients with a previous allergic reaction to isradipine and to other calcium channel blockers of the dihydropyridine type because of the theoretical risk of cross-reactivity or to any of the excipients.Dihydropyridines, including PRESCAL Tablets, should be discontinued in patients who develop cardiogenic shock. They should also not be used in patients with symptomatic or tight aortic stenosis, and during or within one month of myocardial infarction.Dihydropyridines including PRESCAL Tablets should not be used for the prevention of secondary myocardial infarctions (or during or within one month after myocardial infarction) and they have not been approved for the treatment of hypertensive crisis.Dihydropyridines, including PRESCAL Tablets, should not be used in patients with unstable angina

Special Precautions
Individualised dosing of PRESCAL is recommended for elderly patients and patients with renal or hepatic dysfunction or chronic heart failure.As for other calcium antagonists PRESCAL does not give protection against the danger of abrupt beta-blocker withdrawal. Beta-blockers should therefore be withdrawn gradually, preferably over 8-10 days.Caution should be taken when treating patients with documented or strongly suspected sick sinus syndrome who are not fitted with a pacemaker.PRESCAL should be used with caution in patients with poor cardiac reserve.In patients with pre-existing angina pectoris, frequency, duration and severity of anginal attacks may be increased by rapid dosage increments or at the start of treatment.Care is recommended when treating patients with a low systolic blood pressure.There is no evidence that PRESCAL interferes with glucose metabolism, however, diabetic patients should be initially monitored in accordance with good clinical practice.PRESCAL should be discontinued in the event of hypersensitivity to the drug.Concomitant administration with rifampicin or other enzyme inducing drugs should be avoided.Combination of isradipine with cimetidine increases bioavailability of isradipine. Therefore when given concurrently with cimetidine, the dosage of Prescal should be adapted accordingly.

Interactions
Effects of other drugs and/or enzymatic system on PRESCAL:Concurrent administration of rifampicin greatly reduces the plasma concentrations of isradipine. Therefore, concomitant administration with rifampicin or other enzyme-inducing drugs (e.g. anticonvulsants such as carbamazepine and phenobarbital) should be avoided.Increased plasma levels, and potentiation of drug activity and adverse effects (e.g. peripheral oedema), have been reported when dihydropyridines are administered concomitantly with cytochrome P450 3A inhibitors. There is little evidence for such interactions with isradipine, but caution should be exercised when co-administering PRESCAL with strong CYP3A inhibitors such as macrolide antibiotics (e.g. erythromycin, clarithromycin, troleandomycin), HIV protease inhibitors (e.g. ritonavir, indinavir, nelfinavir) or reverse transcriptase inhibitors (e.g. delavirdine), and azole antifungals (e.g. ketoconazole, itraconazole, voriconazole).Concurrent administration of cimetidine increases the bioavailability of isradipine by about 50%.As with all antihypertensives, concomitant treatment with oral baclofen is likely to further increase a possible fall in blood pressure. It may therefore be necessary to monitor blood pressure and adjust the dosage of the antihypertensive medication accordingly.The peak plasma concentration of isradipine increases by about 20% during co-administration with diclofenac but this is not expected to be clinically significant, as steady state exposure remained unchanged.The pharmacokinetics of isradipine are not modified by the concomitant administration of digoxin or hydrochlorothiazide.As with other dihypropyridines, PRESCAL should not be taken with grapefruit juice because bioavailability may be increased.Effects of PRESCAL on other drugs and/or enzymatic systems:PRESCAL does not seem to inhibit the cytochrome P450 enzymes, in particular CYP3A4, to a clinically significant extent. Nor are the kinetics of digoxin, hydrochlorothiazide, diclofenac, theophylline, or triazolam altered by the concomitant administration of PRESCAL.Based on a case report and on the known risks related to the potentiation of phenytoin effects when used in association with calcium channel blockers, concomitant administration with phenytoin should be avoided.

Adverse Reactions
Most side effects are mild and generally dose dependent. Discontinuation of therapy is generally not required.Those side effects mentioned most often are related to the vasodilating properties of PRESCAL: headache, flushing, dizziness, tachycardia, and palpitations and localised peripheral oedema of non-cardiac origin; (local arterial dilatation seems to be involved rather than fluid retention).Adverse reactions observed in clinical trials (occurring more frequently with isradipine than with placebo) and compiled from spontaneous reports are presented below according to system organ class.Adverse reactions are ranked under headings of frequency, the most frequent first, using the following convention: Very common ( 1/10); common ( 1/100, < 1/10); uncommon ( 1/1000, < 1/100); rare ( 1/10,000, < 1/1000); very rare (< 1/10,000), including isolated reports. Within each frequency grouping, adverse reactions are ranked in order of decreasing seriousness.Blood and the lymphatic system disordersVery rare:Thrombopenia, leukopenia, anaemia.Metabolism and nutrition disordersVery rare:Loss of appetite and anorexia.Nervous system disordersVery commonHeadacheCommonDizzinessVery rare:Depression, hypoaesthesia, paraesthesia, anxiety, somnolence, nervousness.Eye disordersVery rare:Visual disturbance, blurred vision.Cardiac disordersCommon:Tachycardia, palpitationsVery rare:Ventricular arrhythmia, myocardial infarction, heart failure.Angina pectoris may occur, predominantly in patients with pre-existing coronary artery disease. Atrial fibrillation, bradycardia.Vascular disordersVery common:Flushing, peripheral oedema.Uncommon:Hypotension.Respiratory, thoracic and mediastinal disordersCommon:DyspnoeaVery rare:CoughGastrointestinal disordersCommon:Abdominal discomfortVery rare:Vomiting, nausea, gingival hyperplasia.Hepato-biliary disordersVery rare:Elevation in liver function tests, isolated cases of hepatitis.Skin and subcutaneous tissue disordersCommon:rashVery rare:Allergic skin reaction, pruritus, sweating, anaphylactic reactions and angioedema, isolated cases of photosensitivity.Musculoskeletal, connective tissue and bone disordersVery rare:Arthralgia, back pain, muscle cramps, pain in limbs.Renal and urinary disordersCommon:PolyuriaReproductive system and breast disordersVery rare:Erectile dysfunction, isolated cases of gynecomastia.General disorders and administration site conditionsCommon:Fatique, malaiseUncommon:Weight gainVery rare:Asthenia,

Manufacturer
Novartis Pharmaceuticals UK Ltd

Drug Availability
(POM)

Updated
29 June 2009