Adult: For temporary control of rapid ventricular rate: Initially, 0.25 mg/kg (average dose: 20 mg) via bolus inj over 2 minutes, may give a further dose of 0.35 mg/kg (average dose: 25 mg) after 15 minutes if response is inadequate. Subsequent doses must be individualised for each patient. For continued heart rate reduction: Following 1-2 bolus inj, initiate infusion at a rate of 5-10 mg/hour, may be increased in increments of 5 mg/hour up to a Max of 15 mg/hour, as needed. May continue infusion for up to 24 hours.
Adult: For rapid conversion to sinus rhythm: Initially, 0.25 mg/kg (average dose: 20 mg) via bolus inj over 2 minutes, may give a further dose of 0.35 mg/kg (average dose: 25 mg) after 15 minutes if needed. Subsequent doses must be individualised for each patient.
Oral Angina pectoris
Adult: Dosage is adjusted carefully according to individual tolerance, response, and requirements. As conventional tab: Initially, 30 mg 4 times daily, may be increased gradually at 1- to 2-day intervals until optimum response is achieved. Usual dose range: 180-360 mg daily. As modified-release tab: Initially, 60 mg tid, may be increased to 360 mg daily if necessary. Max: 480 mg daily. Dosage recommendations may vary depending on the formulation or between countries (refer to specific product guidelines). Elderly: Initially, 120 mg daily as a single or in 2 divided doses, may be increased cautiously but only if the heart rate remains >50 beats/min. Dosage recommendations may vary depending on the formulation or between countries (refer to specific product guidelines).
Oral Hypertension
Adult: Dosage is adjusted carefully according to individual tolerance, response, and requirements. As modified-release tab or cap: Initially, 90-120 mg bid, may be increased as required to a Max of 360 mg daily. Dosage recommendations may vary depending on the formulation or between countries (refer to specific product guidelines). Elderly: Initially, 120 mg daily as a single or in 2 divided doses, may be increased cautiously but only if the heart rate remains >50 beats/min. Dosage recommendations may vary depending on the formulation or between countries (refer to specific product guidelines).
Renal Impairment
Oral:
Initially, 120 mg daily as a single or in 2 divided doses, may be increased cautiously but only if the heart rate remains >50 beats/min. Dosage recommendations may vary depending on the formulation or between countries (refer to specific product guidelines).
Hepatic Impairment
Oral:
Initially, 120 mg daily as a single or in 2 divided doses, may be increased cautiously but only if the heart rate remains >50 beats/min. Dosage recommendations may vary depending on the formulation or between countries (refer to specific product guidelines).
Reconstitution
IV infusion: Further dilute the solution for inj with 0.9% NaCl, 5% dextrose in water, or 5% dextrose in 0.45% NaCl to yield a Max final concentration of 1 mg/mL.
Incompatibility
IV: Physically incompatible (precipitation or cloudiness) with acetazolamide, aciclovir, aminophylline, ampicillin, ampicillin Na + sulbactam Na, cefamandole, cefoperazone, diazepam, furosemide, hydrocortisone Na succinate, insulin (regular: 100 units/mL), methylprednisolone Na succinate, mezlocillin, nafcillin, phenytoin, rifampicin, and Na bicarbonate.
Contraindications
Sick sinus syndrome, 2nd- or 3rd-degree AV block (without a functioning pacemaker), severe bradycardia (<50 beats/min), hypotension (systolic <90 mmHg), decompensated cardiac failure, acute MI and pulmonary congestion. Lactation. Concomitant use with ivabradine. IV: Cardiogenic shock, atrial flutter or fibrillation associated with accessory bypass tract (e.g. Wolff-Parkinson-White syndrome or short PR syndrome), ventricular tachycardia (with wide-complex tachycardia [QRS ≥0.12 seconds]); concomitant use with or within a few hours of IV β-blockers.
Special Precautions
Patient with reduced left ventricular function, bradycardia, 1st-degree AV block, prolonged PR interval (detected on ECG), risk factors for developing intestinal obstruction. Various formulations of diltiazem are available to meet individual requirements of the patient; refer to specific product guidelines when switching formulations. Renal and hepatic impairment. Elderly. Pregnancy.
Adverse Reactions
Significant: AV block, sinus bradycardia, mood changes (e.g. depression), bronchospasm. Rarely, symptomatic hypotension with or without syncope, increased hepatic enzymes (e.g. AST, ALT, lactate dehydrogenase, alkaline phosphatase), hepatic injury, severe cutaneous adverse reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, drug rash with eosinophilia and systemic symptoms, acute generalised exanthematous pustulosis). Cardiac disorders: Palpitations. Gastrointestinal disorders: Nausea, dyspepsia, constipation, gastric pain, vomiting, diarrhoea. General disorders and administration site conditions: Peripheral oedema, malaise; inj site reactions (e.g. itching, burning). Nervous system disorders: Dizziness, headache. Psychiatric disorders: Nervousness, insomnia. Vascular disorders: Flushing.
Monitor blood pressure, ECG, heart rate, LFTs, and kidney function. For IV use, frequently measure blood pressure and continuously monitor ECG.
Overdosage
Symptoms: Hypotension leading to collapse and acute kidney injury; sinus bradycardia (with or without isorhythmic dissociation), sinus arrest, disturbances in atrioventricular (AV) conduction, cardiac arrest. Management: Supportive and symptomatic treatment. Perform gastric lavage and/or osmotic diuresis; administer activated charcoal. Temporary cardiac pacing may be used to manage conduction disturbances. Consider administration of atropine to treat bradycardia and AV block; if no response to vagal blockade, give isoproterenol cautiously. Fluids and vasopressors (e.g. dopamine, norepinephrine) may be used to maintain blood pressure. May administer inotropic agents (e.g. isoproterenol, dopamine, dobutamine) and diuretics in case of cardiac failure.
Drug Interactions
May potentiate the depression of cardiac contractility, conductivity, automaticity, and vascular dilatation induced by anaesthetics. Increased antihypertensive effect with α-antagonists. May increase the depression of cardiac conduction, risk of bradycardia and AV block with β-blockers, amiodarone, or digoxin. Increases plasma concentrations of phenytoin, theophylline, cilostazol, methylprednisolone, carbamazepine, ciclosporin, midazolam, triazolam, buspirone, quinidine. Concomitant use with clonidine may result in sinus bradycardia leading to hospitalisation and insertion of pacemaker. May increase the CV effects (e.g. hypotension) of IV bolus ionic X-ray contrast media. Increased plasma concentrations with cimetidine. May decrease plasma concentrations with CYP3A4 inducers (e.g. rifampicin). May increase the risk of lithium-induced neurotoxicity. Increased risk of myopathy and rhabdomyolysis with statins metabolised by CYP3A4 (e.g. atorvastatin, fluvastatin, simvastatin). Potentially Fatal: Increases the exposure of ivabradine which may exacerbate bradycardia and conduction disturbances.
Food Interaction
May increase serum concentration with grapefruit juice.
Action
Description: Mechanism of Action: Diltiazem is a benzothiazepine derivative Ca channel blocker and class IV antiarrhythmic agent. It inhibits the influx of Ca ions during depolarisation of the vascular smooth muscles and myocardium, thereby producing relaxation of coronary vascular muscles and coronary vasodilation and increases myocardial oxygen delivery. Onset: Oral: 30-60 minutes (conventional tab); IV: Within 3 minutes (bolus). Duration: IV: 1-3 hours (bolus); 0.5-10 hours (continuous infusion; after discontinuation). Pharmacokinetics: Absorption: Almost completely absorbed from the gastrointestinal tract. Bioavailability: Approx 40% (oral). Time to peak plasma concentration: 2-4 hours (conventional tab); 11-18 hours (extended-release tab); 10-14 hours (extended-release cap). Distribution: Rapidly and extensively distributed into body tissues. Enters breast milk. Volume of distribution: 3-13 L/kg. Plasma protein binding: 70-80%. Metabolism: Undergoes extensive first-pass metabolism by CYP450 and conjugation to N-monodesmethyldiltiazem, desacetyldiltiazem, desacetyl-N-monodesmethyldiltiazem, desacetyl-O-desmethyldiltiazem and desacetyl-N,O-desmethydiltiazem. Excretion: Via urine (approx 2-4% as unchanged drug); faeces (as metabolites). Elimination half-life: Oral: 3-4.5 hours (conventional tab); 6-9 hours (extended-release tab); 4-9.5 hours (extended-release cap). IV: Approx 3.4 hours (single dose); 4-5 hours (continuous infusion).
Chemical Structure
Diltiazem Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 39186, Diltiazem. https://pubchem.ncbi.nlm.nih.gov/compound/39186. Accessed Aug. 25, 2022.
Storage
Tab/cap: Store between 15-30°C. Protect from light. Avoid excessive heat and humidity. Solution for inj: Store between 2-8°C. Do not freeze. May store between 15-30°C for up to 1 month. Diluted solutions may be stored between 15-30°C or 2-8°C for 24 hours. Storage recommendations may vary among countries and individual products. Refer to specific product guidelines.
C08DB01 - diltiazem ; Belongs to the class of benzothiazepine derivative selective calcium-channel blockers with direct cardiac effects. Used in the treatment of cardiovascular diseases.
References
Adizem-SR Capsules 90 mg (Napp Pharmaceuticals Limited). MHRA. https://products.mhra.gov.uk. Accessed 06/05/2022.Anon. Diltiazem. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 09/06/2022.Anon. Diltiazem. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/05/2022.Buckingham R (ed). Diltiazem Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/05/2022.Cardizem CD Capsule, Coated, Extended Release (Bausch Health US LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/05/2022.Diltiazem Hydrochloride Capsule, Extended Release (Mylan Pharmaceuticals Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/05/2022.Diltiazem Hydrochloride Injection, Solution; Injection, Powder, Lyophilized, for Solution (Hospira, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/05/2022.Diltiazem Hydrochloride Tablet, Coated (Bausch Health US LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/05/2022.Diltiazem Hydrochloride Tablets 60 mg (Accord-UK Ltd). MHRA. https://products.mhra.gov.uk. Accessed 06/05/2022.Herbesser 60 Tablet (Mitsubishi Tanabe Pharma Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 06/05/2022.Herbesser 90 SR Capsule (Mitsubishi Tanabe Pharma Malaysia Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 06/05/2022.Joint Formulary Committee. Diltiazem Hydrochloride. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/05/2022.Matzim LA Tablet, Extended Release (Actavis Pharma, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 06/05/2022.Tildiem Retard 120 mg Prolonged-release Tablets (Aventis Pharma Limited Trading as: Sanofi). MHRA. https://products.mhra.gov.uk. Accessed 06/05/2022.
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