Editing Diltiazem Hydrochloride (section)

==Drug Management==
'''Drug Interaction: 

Diltiazem is metabolized in the liver by cytochrome P450 3A4 (CYP3A4). Drugs that are known to either inhibit or to induce this enzyme system may therefore alter the first pass (after oral administration) or the clearance of diltiazem.

The extent as well as the duration of interactions should be taken into account when administering diltiazem together with the following drugs:

'''Rifampicin''': Rifampicin strongly induces the cytochrome P450 3A4 system. Risk of decrease of diltiazem plasma levels after initiating therapy with rifampicin. The patient should be carefully monitored when initiating or discontinuing rifampicin treatment.

''Interactions leading to increased plasma concentration of diltiazem

CYP3A4 enzyme inhibitors have been shown to cause an increase in diltiazem plasma concentrations.
In case of clinically significant adverse events due to elevated diltiazem exposure when combined with strong CYP3A4 inhibitors, adjustment of diltiazem dose and/or discontinuation of the CYP3A4 inhibitor should be considered.

Examples:

- Cimetidine

- Erythromycin

- Itraconazole

- Ketoconazole

- Certain flavonoids present in grapefruit juice

Diltiazem tablets should not be taken together with grapefruit juice.

''Interactions leading to decreased plasma concentration of diltiazem

Enzyme inducers of the cytochrome P450 3A4 system have been shown to cause a decrease in plasma concentrations of diltiazem.

In case of lack of efficacy due to decreased diltiazem when combined with potent inducers of CYP3A4, adjustment of diltiazem dose and/or discontinuation of the CYP3A4 inducer should be considered.

Examples:

- Phenytoin

- Carbamazepine

- Rifampicin

- Barbiturates

- Hypericum perforatum (Saint John's wort)

<u>Additional interactions</u>

The simultaneous administration of diltiazem and digoxin/amiodarone may lead to increased risk of bradycardia; caution is required particularly in elderly and when high doses are used.

Diltiazem is an inhibitor of CYP3A4 and has been shown to significantly increase some statins (e.g. atorvastatin and simvastatin). The risk of myopathy and rhabdomyolysis is increased by concomitant administration of diltiazem with statins as mentioned. 

'''Contraindication:'''
 
*Acute porphyrias
*Left ventricular failure with pulmonary congestion
*Second- or third-degree atrioventricular block
*Severe bradycardia
*Sick sinus syndrome

'''Pregnancy:''' avoid

Breast Feeding: significant amount present in milk – no evidence of harm but avoid unless no safer alternative.

Hepatic Impairment: reduce dose

Renal Impairment: start with smaller dose