Calcium channel blockers
Calcium channel blockers
|Alcohol||Additive effect on BP||Verapamil and diltiazem inhibit the metabolism and increase ethanol plasma levels. Alcohol may increase the rate of diltiazem release from the prolonged release preparation.||The effects of alcohol may be exaggerated. Avoid alcohol in patients receiving these CCBs|
|Exert an additive hypotensive effect with verapamil||Verapamil may increase the plasma concentrations of prazosin and terazosin with an additive hypotensive effect.||Close monitoring of blood pressure|
|Anesthetics||Diltiazem and verapamil potentiate the depression of cardiac contractility, AV block, bradycardia and hypotension produced by general anesthetics.||The combination should be avoided.|
|Antiarrhythmics||Increase the risk of bradycardia, AV block, hypotension and heart failure. Coadministration of verapamil with either disopyramide or flecainide increases the risk of myocardial depression and asystole.||Nifedipine decreases the plasma levels of quinidine
Diltiazem and verapamil increase quinidine plasma levels Verapamil may decrease the clearance of flecainide
|The combination should be made with caution. Monitor clinical, hemodynamic and ECG changes.
Diltiazem and verapamil are antiarrhythmics and its co-prescription with other antiarrhythmics is not recommended
|They may potentiate the antihypertensive effect of nifedipine||Cimetidine decreases hepatic blood flow and metabolism and increases the plasma levels of diltiazem, nifedipine, nisoldipine, nitrendipine and verapamil||Reduce the dose of the CCB and monitor BP. Replace cimetidine and ranitidine by famotidine or nizatidine. Amlodipine do not interact with cimetidine|
|Anti-hypertensives||Additive vasodilator response||Monitor BP. Reduce the dosage of other antihypertensives to avoid the risk of hypotension|
|Antineoplastic drugs||Verapamil reduces the resistance to doxorrubicin||Cyclophosphamide, vincristine, procarbazine, doxorubicin and cisplatin reduce the absorption of verapamil||Increase the dose of verapamil. Use another CCB.|
|Aspirin||Coadministration of diltiazem and verapamil with aspirin may increase the risk of bleeding.||Caution with this combination. Monitor the bleeding risk|
- Fluconazole, Itraconazole, Ketoconazole, Posaconazole, Voriconazole
|They inhibit CYP3A4 and increase the plasma levels of CCBs||Appropriate dosage adjustment of the CCB is needed.
The starting dose of atorvastatin should be 10 mg od and the maximum dose 20 mg od.
|Benzodiazepines||The effects of midazolam and triazolam are markedly increased by diltiazem or verapamil||Diltiazem and verapamil inhibit CYP3A4 and increase the plasma levels of midazolam and triazolam||Special care in patients treated with these short-acting benzodiazepines. This interaction does not occur with diazepam. Diltiazem does not interact with temazepam.|
|Beta-blockers||Additive effects on BP (hypotension), heart rate (bradycardia), AV conduction and/or cardiodepressant effects when combined with verapamil or diltiazem.||Diltiazem increases the bioavailability of oral propranolol.
Verapamil may increase the plasma concentrations of metoprolol and propranolol.
|Coadministration of β-blockers with DHP-CCBs is usually well tolerated.
This combination should be administered under close medical (ECG) supervision, particularly at the beginning of treatment.
Verapamil is best combined with atenolol or nadolol that are excreted by renal route than with β-blockers that are metabolized in the liver (carvedilol, metoprolol, propranolol).
IV β-blockers should not be given in patients treated with diltiazem or verapamil.
|Bile-acid binding resins||Reduce the bioavailability of diltizem and verapamil||Monitor the response to CCBs. Separate the doses of CCB and resins by about 2 hours.|
|Boceprevir||The maximum dose of atorvatatin should be limited to 40 mg.|
|Buspirone||Diltiazem increases the AUC and the elimination time of buspirone||Dose adjustments are needed.|
|Calcium salts||Antagonize the antiarrhythmic effects of CCBs||Monitor for a reduced response when large doses of calcium are given|
|Calcium channel blockers||Diltiazem can be combined with DHPs in patients with resistant coronary artery vasospasm||Diltiazem increases nifedipine plasma levels||Monitor for increased nifedipine effects|
|Carbamazepine||Increase carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia)||Some CCBs (diltiazem) can inhibit CYP3A4 and increases carbamazepine plasma levels||Monitor the plasma levels and reduce the dosage of carbamazepine|
|Clonidine||Cases of bradycardia and complete AV block when diltiazem or verapamil and clonidine are combined||No interaction exist between nifedipine and clonidine|
|Colchicine||Cases of myopathy, including rhabdomyolysis, when atorvastatin and colchicine are co-administered||Verapamil inhibits CYP3A4 and P-gp and increases the exposure to colchicine||This combination is not recommended.|
|Corticosteroids (methylprednisolone)||Diltiazem can increase methylprednisolone levels through inhibition of CYP3A4 and P-gp||Monitor the patient when initiating methylprednisolone treatment. Adjustment of the methylprednisolone dose may be necessary.|
|Cytochrome P450 3A inducers:
- St John's wort)
|Decrease the effects of CCBs||They increase the metabolism and decrease the plasma levels of CCBs||Increase the doses of CCBs as appropriate. Patients should be carefully monitored where initiating or discontinuing the inducer.|
|Dabigitran etexilate||Verapamil increases the Cmax and AUC of dabigatran when both drugs are coadministred. However, no chages are observed when verapamil was administered 2 hours after dabigatran etexilate||Close clinical surveillance is recommended when both drugs are combined, particularly in patients at risk of bleeding (mild to moderate renal impairment)|
|Dantrolene (I.V.)||The combination with verapamil increases the risk of hypotension, myocardial depression and hyperkalemia. Ventricular fibrillation when combined with verapamil||This combination should be avoided.|
|Digoxin||Increased risk of bradycardia and AV block||Bepridil, nifedipine, nitrendipine, nisoldipine and verapamil inhibit digoxin clearance, reduce its volume of distribution and increase digoxin plasma levels. Diltiazem does not interact with digoxin.||Monitor digoxin plasma levels and the ECG. reduce the maintenance dose of digoxin.|
|Dofetilide||Increases the risk of arrhythmias||CCBs increase dofetilide plasma levels||The combination is contraindicated.|
|Diuretics||Additive antihypertensive effects||Reduce the dosage as appropriate to avoid the risk of hypotension.|
|Ezetimibe||The risk of muscular events increases with concomitant use of ezetimibe and atorvastatin||Clinical monitoring is recommended.|
|Fentanyl||Diltiazem and verapamil increase or prolong their effects and may cause potentially fatal respiratory depression||Diltiazem and verapamil inhibit CYP3A4 increasing fentanyl exposure||The doses of fentanyl should be carefully monitored, and adjusted as needed|
|Fibrates||Increased risk of muscular adverse effects||Use the lowest dose of atorvastatin. Patients should be appropriately monitored|
|Fluoxetine||It increases the adverse effects of CCBs||Fluoxetine reduces the clearance and increases CCB plasma levels||Reduce the dose of CCBs if necessary|
|Grapefruit juice||Inhibits CYP3A4 and increases the plasma levels of felodipine, nicardipine, nifedipine, nimodipine, nitrendipine, nisoldipine and verapamil||Avoid grapefruit juice. Amlodipine and diltiazem plasma levels are only minimally affected.|
|Halofantrine||Increased risk of QT interval prolongation and ventricular arrhythmias||Verapamil and diltiazem inhibit CYP450 3A4 and increase halofantrine plasma levels||Monitor the ECG for 8-12 hours after completion of therapy|
|Hepatitis C protease inhibitor
|The maximum dose of atorvatatin should be limited to 40 mg.|
|Imipramine||Increased risk of hypotension, AV block and cardiodepression||Diltiazem and verapamil decrease the clearance of imipramine and increase its plasma levels||Monitor the patients for increased imipramine toxicity (tachycardia, dry mouth, sedation) and ECG (AV block). Reduce the dosage of diltiazem/verapamil|
|Increase the adverse effects of the immunosupressants||Diltiazem, nicardipine, nifedipine and verapamil inhibit the metabolism of the immunosuppressants and increase their plasma levels.
Diltiazem and verapamil increase the oral absorption and exposure to everolimus
Cyclosporin inhibits CYP3A4 and increases the plasma levels of CCBs.
|Frequent monitoring of BP and adjust the dose as appropriate.
The plasma levels of these drugs should be closely monitored.
Reduce the dose of immunosuppressants.
Cyclosporin plasma levels and renal function should be closely monitored. Amlodipine does not present this interaction.
|Ivabradine||Additional slowing of heart rate when coadministered with diltiazem or verapamil||Avoid this combination|
|Lithium||Diltiazem and verapamil increases the risk of lithium-induced neurotoxicity||Monitor the plasma levels and neurotoxic effects of lithium. Dose adjustments are needed.|
|Increase the effects of CCBs. Telithromycin produces hypotension and bradycardia when combined with verapamil||Macrolides inhibit CYP3A4 and increases the bioavailability of some CCBs (verapamil)||Reduce the dose of CCBs if these macrolides are prescribed.
The starting dose of atorvastatin should be 10 mg od and the maximum dose 20 mg od.
|Nefazodone||Nefazodone inhibits the CYP 3A4 and increases plasma levels of nifedipine||Monitor blood pressure when both drugs are coadministrated. Consider to reduce the dose of nifedipine|
|Neuromuscular blockers||Some CCBs can reduce the release of acetylcholine and potentiate the neuromuscular blockade of pancuronium||Risk for an increased neuromucular blockade during surgery|
|Nitrates||Additive vasodilator effects||Increase the dosage of nitrates gradually. Monitor BP|
|Phenothiazines||Additive vasodilator effects||Increased risk of hypotension. Monitor BP|
|Phenytoin||Increase phenytoin toxicity (e.g., drowsiness, visual disturbances, change in mental status, seizures, nausea, or ataxia)||Diltiazem and verapamil inhibit CYP3A4 and increase phenytoin plasma levels. Phenytoin induces CYP 3A4 and may decrease the plasma levels of nifedipine and verapamil||Monitor the effects and plasma levels of phenytoin.
Increase the dose of nifedipine. Reduce the dose of nifedipine when phenytoin is discontinued.
|Pimozide||Increases the risk of proarrhythmia||Diltiazem and verapamil increase plasma levels of pimozide||Avoid the combination|
|Ranolazine||Diltiazem and verapamil increase the plasma levels of ranolazine||Careful dose titration of ranolazine is recommended|
|Sildenafil||CCBs increase its plasma levels||Reduce the doses of these drugs|
|Increased incidence of muscular disorders||Diltiazem, isradipine and verapamil inhibit CYP3A4 and increases the plasma levels of these statins.
Atorvastatin increases verapamil levels.
|Treatment with simvastatin, atorvastatin or lovastatin in a patient taking verapamil should be started at the lowest possible dose and titrated upwards. Max dose of simvastatin: 10-20 mg/day.
Use fluvastatin, pravastatin, and rosuvastatin that are not metabolized by CYP3A4.
Caution when atorvastatin and verapamil are concomitantly administered.
|Sulfinpyrazone||Antagonizes the antihypertensive effect of verapamil||Reduce the plasma concentrations of verapamil||Avoid the combination|
|Theophylline||CCBs increase the adverse effects of theophylline||Diltiazem and verapamil reduce its clearance and increase its plasma levels||Monitor theophylline plasma levels. The dose of diltiazem and verapamil should be adjusted if necessary.|
|Tobacco||Reduces the antianginal effect of CCBs||Patient must stop smoking|
|VIH protease inhibitors:
- Atazanavir, Indinavir, Nelfinavir, Ritonavir, Saquinavir
-Saquinavir+ritonavir, darunavir+ritonavir, lopinavir+ritonavir, fosamprenavir+ritonavir
|Prolong the PR interval of the ECG. Orthostatic hypotension with the combination of nelfinavir or ritonavir/indinavir and nifedipine||They increase the bioavailability of diltiazem and verapamil.||Ritonavir and saquinavir should not be used with other agents that prolong the PR interval
The starting dose of atorvastatin should be 10 mg od and the maximum dose 20 mg od
|Warfarin||Atorvastatin (80 mg/day) causes a small decrease in prothrombin time which returned to normal within 15 days of treatment.||Uncertain clinical meaning|
|Vitamin D (at high doses)||May reduce the response to CCBs||Monitor the effects of CCBs|
BP: blood pressure
CCB: calcium channel blocker
Cmax: peak plasma levels
AUC: area under the curve