Symptoms
The clinical effects of acute overdose can involve pronounced hypotension possibly leading to collapse, sinus bradycardia with or without isorhythmic dissociation, and atrioventricular conduction disturbances. It is recommended that patients with suspected overdose should be placed under observation in a coronary care unit.
Most patients suffering from overdosage of diltiazem become hypotensive within 8 hours of ingestion. With bradycardia and first to third degree atrioventricular block also developing, cardiac arrest may ensue. Hyperglycaemia is also a recognised complication. The elimination half-life of diltiazem after overdosage is estimated to be about 5.5-10.2 hours.
The following may be linked to renal impairment in patients; polyuri, pollakiuria, nocturia, acute kidney injury, acute interstitiel nephritis.
Management
Treatment, in a hospital setting, will include gastric lavage with administration of activated charcoal to reduce diltiazem absorption and/or osmotic diuresis. Conduction disturbances may be managed by temporary cardiac pacing. Proposed corrective treatments: Hypotension should be corrected with plasma expanders, vasopressors, glucagon, calcium gluconate infusion and inotropic agents (e.g. dopamine, dobutamine or isoprenaline). Symptomatic bradycardia and high grade AV block may respond to atropine, isoprenaline or occasionally cardiac pacing which may be useful if cardiac standstill occurs.
Diltazem SR SR capsules are prolonged release capsules and effects may be slow in onset and prolonged, therefore, monitoring should be carried out for longer periods than following overdose with immediate-release dosage forms.
â–ª
â–ª Pregnancy and in women of child bearing potential
â–ª Severe bradycardia (below 40 bpm)
â–ª Second- or third-degree AV block except in the presence of a functioning ventricular pacemaker
â–ª Sick sinus syndrome except in the presence of a functioning ventricular pacemaker
â–ª Cardiac failure after myocardial infarction
â–ª Left ventricular failure with pulmonary congestion
â–ª Concomitant administration of dantrolene infusion
â–ª Combination with ivabradine
Not applicable.
The following CIOMS frequency rating is used, when applicable: 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).
Within each frequency grouping, adverse events are presented in order of decreasing seriousness.
| Very Common | Common | Uncommon | Rare | Not Known | |
| Blood and lymphatic system disorders | Thrombocytopenia | ||||
| Immune system disorders | Hypersensitivity | ||||
| Psychiatric disorders | Nervousness, insomnia | Mood changes (including depression), anorexia | |||
| Nervous system disorders | Headache, dizziness | Extrapyramidal syndrome, Parkinsonian syndrome, paraesthesia | |||
| 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) Hypotension | ||
| Gastrointestinal disorders | Constipation, dyspepsia, gastric pain, nausea | Vomiting, diarrhoea | Dry mouth | Gingival hyperplasia Gastrointestinal disorder | |
| Hepatobiliary disorders | Hepatic enzymes increase (AST, ALT, LDH, ALP increase) | Hepatitis | |||
| Skin and subcutaneous tissue disorders | Erythema, pruritus | 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 generalised exanthematous pustulosis, desquamative erythema with or without fever, allergic dermatitis hyperpigmentation | ||
| Reproductive system and breast disorders | Gynecomastia | ||||
| General disorders and administration site conditions | Peripheral oedema | Malaise, fatigue |
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 the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
There are no additional data of relevance to the prescriber.
The treatment of angina pectoris.
The treatment of mild to moderate hypertension.
Diltazem SR SR capsules are indicated for use in adults only.
Pharmacotherapeutic group: Selective calcium channel blockers with direct cardiac effects:
ATC code: C08DB01
Diltiazem hydrochloride is a calcium-channel blocking agent. It is a peripheral and coronary vasodilator with some negative inotropic activity. Diltiazem inhibits cardiac conduction particularly at the sino-atrial and atrioventricular nodes. It is used in the management of classical and vasospastic angina pectoris and it is also used in the treatment of essential hypertension.
Absorption
Diltiazem is rapidly and almost completely absorbed from the gastro-intestinal tract following oral administration, but undergoes extensive first-pass hepatic metabolism. The bioavailability has been reported to be about 40%, although there is considerable inter-individual variation in plasma concentrations.
Distribution
Diltiazem is about 80% bound to plasma proteins.
Biotransformation
It is extensively metabolised in the liver; one of the metabolites, desacetyl diltiazem has been reported to have 25 to 50% of the activity of the parent compound. The half-life is reported to be about 3 to 4 hours.
Elimination
Approximately 60% of the dose is excreted in the bile and 35 to 40% in the urine, and 2 to 4% as unchanged diltiazem.
The prolonged-release formulation is designed for twice daily dosage.
Rare instances of hyperglycaemia have been reported in association with diltiazem hydrochloride. The use of diltiazem in diabetic patients may require adjustment of their control.
Precaution should be taken in patients with reduced left ventricular function. Patients should be observed closely if they have bradycardia (risk of exacerbation), first degree AV block detected on the electrocardiogram (risk of exacerbation and rarely, of complete block) or prolonged PR interval.
Diltiazem is considered unsafe in patients with acute porphyria.
Prior to general anaesthesia, the anaesthetist must be informed of ongoing diltiazem treatment. Depression of cardiac contractility, conductivity and automaticity, as well as the vascular dilatation associated with anaesthetics may be potentiated by calcium channel blockers.
Increase of plasma concentrations of diltiazem may be observed in the elderly and in patients with renal or hepatic insufficiency. The contraindications and precautions should be carefully observed and close monitoring, particularly of heart rate, should be carried out at the beginning of treatment.
Calcium channel blocking agents, such as diltiazem, may be associated with mood changes, including depression.
Like other calcium channel antagonists, diltiazem has an inhibitory effect on intestinal motility. Therefore it should be used with caution in patients at risk to develop an intestinal obstruction. Tablet residues from slow release formulations of the product may pass into the patient's stools; however, this finding has no clinical relevance.
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
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.
Posology
Angina
Adults: the usual initial dose is 90 mg twice daily. Dosage may be increased gradually to 120 mg twice daily or 180 mg twice daily if required. Patients' responses may vary and dosage requirements can differ significantly between individual patients.
Hypertension
Adults: the usual dose is 120 mg once or twice daily. Patients may benefit by titrating from a lower total daily dose.
Paediatric population
The safety and efficacy in children has not been established. Therefore diltiazem is not recommended for use in children.
Dosage in the elderly and patients with impaired hepatic or renal function
Angina
Dosage should commence at 60 mg twice daily and the dose carefully titrated as required.
Hypertension
Dosage should commence at the lower level of 60 mg twice daily and be increased slowly in order to achieve the required level of control. The daily dose should not exceed 90 mg twice daily. Do not increase the dose if the heart rate falls below 50 beats per minute.
Method of administration
For oral use.
Capsules should be swallowed whole with water and should not be sucked, chewed or crushed.
No special requirements.
