This information is intended for use by health professionals
Adults240mg once dailyDosage titration in 60mg to 120mg steps at 2-weekly intervals may be required to obtain satisfactory clinical response (usually 240mg to 360mg daily will suffice). Dosage should be reduced in the presence of adverse reactions or if the pulse rate falls below 50 per minute.
Older people and patients with hepatic or renal impairmentStarting dose 120mg once daily.
Paediatric populationNot recommended
Concomitant use contraindicated:Dantrolene (infusion): Lethal ventricular fibrillation is regularly observed in animals when intravenous verapamil and dantrolene are administered concomitantly. The combination of a calcium antagonist and dantrolene is therefore potentially dangerous (see section 4.3).Ivabradine: Concomitant use with ivabradine is contraindicated due to the additional heart rate lowering effect of diltiazem to ivabradine (see section 4.3).
Concomitant use requiring caution:Lithium: Risk of increase in lithium-induced neurotoxicityNitrate derivatives: Increased hypotensive effects and faintness (additive vasodilatating effects): In all the patients treated with calcium antagonists, the prescription of nitrate derivatives should only be carried out at gradually increasing doses.Theophylline: Increase in circulating theophylline levels. Care should be exercised in patients taking these drugs.Alpha-antagonists: Increased antihypertensive effects:Concomitant treatment with alpha-antagonists such as prazosin may produce or aggravate hypotension. The combination of diltiazem with an alpha-antagonist should be considered only with the strict monitoring of the blood pressure.Amiodarone, digoxin: Increased risk of bradycardia, small increases in plasma levels of digoxin. Caution is required when these are combined with diltiazem, particularly in elderly subjects and when high doses are used.Beta-blockers: 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.Other antiarrhythmic agents: Since diltiazem has antiarrhythmic properties, its concomitant prescription with other antiarrhythmic agents is not recommended (additive risk of increased cardiac adverse effects). This combination should only be used under close clinical and ECG monitoring.Carbamazepine: Increase in circulating carbamazepine levels: It is recommended that the plasma carbamazepine concentrations be assayed and that the dose should be adjusted if necessary.Rifampicin: Risk of decrease of diltiazem plasma levels after initiating therapy with rifampicin: The patient should be carefully monitored when initiating or discontinuing rifampicin treatment.Anti-H2 agents (cimetidine, ranitidine): 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. Ciclosporin: Increase in circulating cyclosporin levels: It is recommended that the cyclosporin dose be reduced, renal function be monitored, circulating cyclosporin levels be assayed and that the dose should be adjusted during combined therapy and after its discontinuation. Tricyclic antidepressants: diltiazem increases plasma concentration of imipramine. Diltiazem possibly increases plasma concentration of tricyclic antidepressants.
General information to be taken into account:Due to the potential for additive effects, caution and careful titration are necessary in patients receiving diltiazem concomitantly with other agents known to affect cardiac contractility and/or conduction.Diltiazem is metabolized 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. 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. Co-administration of diltiazem with a CYP3A4 inducer may result in a decrease of diltiazem plasma concentrations.Benzodiazepines (midazolam, triazolam): Diltiazem significantly increases plasma concentrations of midazolam and triazolam and prolongs their half-life. Special care should be taken when prescribing short-acting benzodiazepines metabolized by the CYP3A4 pathway in patients using diltiazem.Corticosteroids (methylprednisolone): Inhibition of methylprednisolone metabolism (CYP3A4) and inhibition of P-glycoprotein: The patient should be monitored when initiating methylprednisolone treatment. An adjustment in the dose of methylprednisolone may be necessary.Statins: Diltiazem is an inhibitor of CYP3A4 and has been shown to significantly increase the AUC of some statins. The risk of myopathy and rhabdomyolysis due to statins metabolised by CYP3A4 may be increased with concomitant use of diltiazem. When possible, a non CYP3A4-metabolised statin should be used together with diltiazem, otherwise close monitoring for signs and symptoms of a potential statin toxicity is required.Oral administration of diltiazem can raise blood levels of drugs exclusively metabolised by the iso-enzyme CYP3A4 this can lead to increased plasma levels for carbamazepine, tacrolimus, sirolimus, and erythromycin.
PregnancyThere is very limited data from the use of diltiazem in pregnant patients.Diltiazem has been shown to have reproductive toxicity (teratogenic) in some animal species (rat, mice, rabbit). In the absence of adequate evidence of safety in human pregnancy, dilitiazem is therefore not recommended during pregnancy as well as in women of child- bearing potential not using effective contraception.
Breast-feedingDiltiazem hydrochloride is excreted in breast milk at low concentrations. One report suggests that concentrations in breast milk reach similar levels to those in serum. Breast-feeding while taking this drug should be avoided. If use of diltiazem is considered medically essential, an alternative method of infant feeding should be instituted.
|Very common||Common||Uncommon||Rare||Not known|
|Blood and lymphatic system disorders||Thrombocytopenia|
|Psychiatric disorders||Nervousness, insomnia||Mood changes (including depression)|
|Nervous system disorders||Headache, dizziness||Extrapyramidal syndrome. Drug-induced Parkinsonism|
|Cardiac disorders||Atrioventricular block (may be of first, second or third degree; bundle branch block may occur), palpitations||Bradycardia||Sinoatrial block, congestive heart failure|
|Vascular disorders||Flushing||Orthostatic hypotension||Vasculitis (including leukocytoclastic vasculitis)|
|Gastrointestinal disorders||Constipation, dyspepsia, gastric pain, nausea||Vomiting, diarrhea||Dry mouth||Gingival hyperplasia|
|Hepatobiliary disorders||Hepatic enzymes increase (AST, ALT, LDH, ALP increase)||Hepatitis|
|Skin and subcutaneous tissue disorders||Erythema||Urticaria||Photosensitivity (including lichenoid keratosis at sun exposed skin areas), angioneurotic oedema, rash, erythema multiforme (including Steven-Johnson's syndrome and toxic epidermal necrolysis), sweating, exfoliative dermatitis, acute generalized exanthematous pustulosis and hyperpigmentation in sun-exposed areas have also been reported. Occasionally desquamative erythema with or without fever.|
|Reproductive system and breast disorders||Gynecomastia|
|General disorders and administration site conditions||Peripheral oedema||Malaise|
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important.It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
Signs and symptoms:The clinical effects of acute overdose can involve pronounced hypotension possibly leading to collapse, sinus bradycardia with or without isorhythmic dissociation, atrioventricular conduction disturbances and on occasions, to cardiac arrest.Hyperglycaemia may require treatment. Onset of symptoms may be delayed for several hours after ingestion and have been described after as little as 900mg diltiazem.
Treatment:Treatment in a hospital setting will include gastric lavage and/or osmotic diuresisObservation in a coronary or intensive care unit is advisable if a substantial overdose has been ingested. Soon after ingestion, gastric lavage followed by activated charcoal may reduce absorption.Profound hypotension requires plasma expanders, I V calcium gluconate and inotropic agents (e.g. dopamine, dobutamine or isoprenaline). Symptomatic bradycardia and heart block may respond to atropine, vasopressors, inotropic agents, isoprenaline, glucagon, calcium gluconate infusion or, if necessary, cardiac pacing. Slozem capsules are extended release capsules and effects may be slow in onset and prolonged.
|Slozem 120mg Capsules||PL 11648/0045|
|Slozem 180mg Capsules||PL 11648/0046|
|Slozem 240mg Capsules||PL 11648/0047|
|Slozem 300mg Capsules||PL 11648/0042|