Chemical formula: C₂₂H₂₆N₂O₄S Molecular mass: 414.518 g/mol PubChem compound: 39186
Diltiazem interacts in the following cases:
Concomitant treatment of diltiazem with alpha-antagonists may produce or aggravate hypotension. The combination of diltiazem with an alpha antagonist should be considered only with strict monitoring of blood pressure.
Co-administration of diltiazem with a CYP3A4 inducer may result in a decrease of diltiazem plasma concentrations.
Diltiazem is also a CYP3A4 isoform inhibitor. Co-administration with other CYP3A4 substrates may result in an increase in plasma concentration of either co-administered drug.
Grapefruit juice may increase diltiazem exposure (1.2 fold). Patients who consume grapefruit juice should be monitored for increased adverse effects of diltiazem. Grapefruit juice should be avoided if an interaction is suspected.
Diltiazem is metabolised by CYP3A4. A moderate (less than 2-fold) increase of diltiazem plasma concentration in cases of co-administration with a stronger CYP3A4 inhibitor has been documented.
Increase in plasma diltiazem concentrations. Patients currently receiving diltiazem therapy should be carefully monitored when initiating or discontinuing therapy with anti-H2 agents. An adjustment in diltiazem daily dose may be necessary.
In a pharmacodynamic study, diltiazem was shown to inhibit platelet aggregation. Although the clinical significance of this finding is unknown, potential additive effects when used with antiplatelet drugs should be considered.
Since diltiazem has antiarrhythmic properties, its concomitant prescription with other antiarrhythmic agents is not recommended due to the risk of increased cardiac adverse effects due to an additive effect. This combination should only be used under close clinical and ECG monitoring.
Increased hypotensive effects and faintness (additive vasodilating effects).
In all patients treated with calcium antagonists, the prescription of nitrate derivatives should only be carried out at gradually increasing doses.
Possibility of rhythm disturbances (pronounced bradycardia, sinus arrest), sino-atrial and atrio-ventricular conduction disturbances and heart failure (synergistic effect). Such a combination must only be used under close clinical and ECG monitoring, particularly at the beginning of treatment. An increased risk of depression has been reported when dilitiazem is co-administered with beta-blockers.
Protease inhibitors (e.g. atazanavir, ritonavir) increase in plasma diltiazem concentrations.
Diltiazem significantly increases plasma concentrations of midazolam and triazolam and prolongs their half-life. Special care should be taken when prescribing short-acting benzodiazepines matabolised by the CYP3A4 pathway in patients using diltiazem.
Cardiovascular effects of an intravenous bolus of an ionic X-ray contrast media, such as hypotension, may be increased in patients treated with diltiazem. Special caution is required in patients who concomitantly receive diltiazem and X-ray contrast media.
Increased risk of bradycardia; caution is required when these are combined with diltiazem, particularly in elderly subjects and when high doses are used.
Co-administration of diltiazem with carbamazepine causes an increase in plasma carbamazepine levels. It is recommended that the plasma carbamazepine concentrations be assayed and that the dose should be adjusted if necessary.
Increase in circulating ciclosporin levels. It is recommended that the ciclosporin dose be reduced, renal function be monitored, circulating ciclosporin levels be assayed and that the dose should be adjusted during combined therapy and after its discontinuation.
Inhibition of cilostazol metabolism (CYP3A4). Diltiazem has been shown to increase cilostazol exposure and to enhance its pharmacological activity.
Risk of increase in lithium-induced neurotoxicity during co-administration of lithium with diltiazem.
Diltiazem can increase methylprednisolone levels (through inhibition of CYP3A4 and possible inhibition of P-glycoprotein). The patient should be monitored when initiating methylprednisolone treatment. An adjustment to the dose of methylprednisolone may be necessary.
When co-administered with phenytoin, diltiazem may increase phenytoin plasma concentration. It is recommended that the phenytoin plasma concentrations be monitored.
Risk of decrease of diltiazem plasma levels after initiating therapy with rifampicin. The patient should be carefully monitored when initiating or discontinuing rifampicin treatment.
Increase in circulating theophylline levels during co-administration of theophylline with diltiazem.
The use of diltiazem may induce bronchospasm, including asthma aggravation, especially in patients with preexisting bronchial hyper-reactivity. Cases have also been reported after dose increase. Patients should be monitored for signs and symptoms of respiratory impairment during diltiazem therapy.
Diltiazem has an inhibitory effect on intestinal motility. Therefore it should be used with caution in patients at risk of developing an intestinal obstruction.
There are very limited data from the use of diltiazem in pregnant patients. Diltiazem has been shown to have reproductive toxicity in certain animal species (rat, mice, rabbit). Diltiazem is therefore not recommended during pregnancy, as well as in women of child-bearing potential not using effective contraception.
As this drug is excreted in breast milk, breast feeding whilst taking diltiazem is contraindicated.
On the basis of reported adverse drug reactions, i.e. dizziness (common), malaise (common), the ability to drive and use machines could be altered. However, no studies have been performed.
The following frequencies are the basis for assessing undesirable effects: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000); Not known (cannot be estimated from the available data).
Not known: Thrombocytopenia
Uncommon: Hypersensitivity
Uncommon: Nervousness, insomnia
Not known: Mood changes (including depression)
Common: Headache, dizziness
Not known: Extrapyramidal syndrome
Common: Atrioventricular block (may be of first, second or third degree; bundle branch block may occur), palpitations
Uncommon: Bradycardia
Not known: Sinoatrial block, congestive heart failure
Common: Flushing
Uncommon: Orthostatic hypotension
Not known: Vasculitis (including leukocytoclastic vasculitis), hypotension
Common: Constipation, dyspepsia, gastric pain, nausea
Uncommon: Vomiting, diarrhoea
Rare: Dry mouth
Not known: Gingival hyperplasia
Uncommon: Hepatic enzymes increase (AST, ALT, LDH, ALP increase)
Not known: Hepatitis
Common: Erythema, Pruritus
Rare: Urticaria
Not known: Photosensitivity (including lichenoid keratosis at sun exposed skin areas), angioneurotic oedema, rash, erythema multiforme (including Steven-Johnson’s syndrome and toxic epidermal necrolysis), hyperhidrosis, exfoliative dermatitis, acute generalized exanthematous pustulosis, occasionally desquamative erythema with or without fever, allergic dermatitis
Not known: Gynecomastia
Very common: Peripheral oedema
Common: Malaise, fatigue
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