Isradipine

In patients with impaired hepatic or renal function, a more suitable starting dose is 2.5 mg once a day.

The concomitant intake of grapefruit juice may increase the bioavailability of isradipine.

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 coadministering isradipine 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).

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.

Concurrent administration of cimetidine increases the bioavailability of isradipine by about 50%.

When isradipine is given concurrently with cimetidine, the dose of isradipine should be reduced by 50%.

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.

Based on a case report and on the known risks related to the co-administration of phenytoin with calcium channel blockers, concomitant administration with phenytoin should be avoided.

Isradipine induces a small (27%) increase in the bioavailability (AUC) of propranolol. The clinical relevance is not known.

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, phenobarbital) should be avoided.

Caution should be exercised when treating patients with confirmed or strongly suspected sick sinus syndrome who are not fitted with a pacemaker.

Care is recommended when treating patients with low systolic blood pressure.

Extreme caution is advised when giving dihydropyridines to patients with severe aortic stenosis.

There is limited information on the use ofisradipine in pregnant women. Data on a limited number of pregnant women exposed to isradipine in the third trimester indicate no adverse effects of isradipine on pregnancy or on the health of the fetus or neonate. Animal studies do not show any directly or indirectly harmful effects on pregnancy, embryofetal development, parturition or postnatal development at therapeutically relevant dose levels. The oral use of isradipine in the third trimester has not been associated with any change in fetal heart rate or uteroplacental blood flow and the tocolytic effect seems to be weak.

The risk to the fetus/mother is unknown. Because animal reproductive toxicity studies are not always predictive of human response, isradipine should be used during pregnancy only if clinically indicated and only if the expected benefit outweighs the potential risk to the fetus.

There is limited information on the use of isradipine in breast-feeding women. In a study in rats it was shown that small amounts of isradipine pass into the milk. Animal experiments have not shown isradipine to have any adverse effects when administered during lactation. It is unknown whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when isradipine is administered to a breastfeeding woman.

Women of child-bearing potential

There are no data supporting any special recommendations in women of child-bearing potential.

Fertility

Animal studies do not show any harmful effects on fertility.

There are no data on the effects of isradipine on the ability to drive or use machines.As with other calcium channel blockers, syncope, dizziness, hypotension, visual disturbances and blurred vision are known adverse drug reactions associated with the use of isradipine. Patients should not drive a vehicle or operate a machine or perform tasks that require alertness if they experience these symptoms.