Formulary
Diltiazem hydrochloride: Indications, Dosing, Side Effects and Interactions
For all calcium-channel blockers Calcium-channel blockers (less correctly called 'calcium-antagonists') interfere with the inward displacement of calcium ions...
MedNext Academy | 6 min read
Diltiazem hydrochloride: Indications, Dosing, Side Effects and Interactions
For all calcium-channel blockers Calcium-channel blockers (less correctly called 'calcium-antagonists') interfere with the inward displacement of calcium ions...
Drug action
For all calcium-channel blockers Calcium-channel blockers (less correctly called 'calcium-antagonists') interfere with the inward displacement of calcium ions through the slow channels of active cell membranes. They influence the myocardial cells, the cells within the specialised conducting system of the heart, and the cells of vascular smooth muscle. Thus, myocardial contractility may be reduced, the formation and propagation of electrical impulses within the heart may be depressed, and coronary or systemic vascular tone may be diminished.
Indications and dose
**Prophylaxis and treatment of angina**
- **Adult** (By Mouth): Initially 60 mg 3 times a day, adjusted according to response; maximum 360 mg per day.
- **Elderly** (By Mouth): Initially 60 mg twice daily, adjusted according to response; maximum 360 mg per day.
**Chronic anal fissure**
- **Adult** (By Rectum Using Cream, Or By Rectum Using Ointment): Apply twice daily until pain stops. Max. duration of use 8 weeks, apply to the anal canal, using 2% topical preparation.
- **Adult** (By Mouth): 60 mg twice daily until pain stops. Max. duration of use 8 weeks.
**Mild to moderate hypertension**
- **Adult** (By Mouth): 180-300 mg once daily, increased if necessary to 360 mg once daily.
- **Elderly** (By Mouth): Initially 120 mg once daily, increased if necessary to 360 mg once daily.
**Angina**
- **Adult** (By Mouth): 180-300 mg once daily, increased if necessary to 480 mg once daily.
- **Elderly** (By Mouth): Initially 120 mg once daily, increased if necessary to 480 mg once daily.
**Angina,Mild to moderate hypertension**
- **Adult** (By Mouth): Initially 180 mg once daily, adjusted according to response to 240 mg once daily; maximum 360 mg per day.
- **Elderly** (By Mouth): Initially 120 mg once daily, adjusted according to response.
**Raynaud's syndrome for diltiazem hydrochloride**
- **Child 12-17 years** (By mouth): 30-60 mg 2-3 times a day.
Cautions
For all calcium-channel blockers Elderly Cautions, further information Elderly Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) criteria to aid medication reviews (see Prescribing in the elderly for information): potentially inappropriate with persistent postural hypotension i.e. recurrent drop in systolic blood pressure 20 mmHg (risk of syncope and falls). Cautions For diltiazem hydrochloride With systemic use Bradycardia (avoid if severe); first degree AV block; prolonged PR interval; significantly impaired left ventricular function Cautions, further information Systemic absorption following rectal use is unknown, therefore consider the possibility of cautions listed for systemic use. Elderly Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) criteria to aid medication reviews (see Prescribing in the elderly for information): potentially inappropriate in patients with NYHA Class III or IV heart failure (contra-indicated in heart failure with reduced ejection fraction; may worsen heart failure).
Contraindications
With systemic use Acute porphyrias ; cardiogenic shock; heart failure (with reduced ejection fraction); left ventricular failure with pulmonary congestion; second- or third-degree AV block (unless pacemaker fitted); severe bradycardia; sick sinus syndrome; significant aortic stenosis Contra-indications, further information Systemic absorption following rectal use is unknown, therefore consider the possibility of contra-indications listed for systemic use.
Side effects
For all calcium-channel blockers Common or very common Abdominal pain; dizziness; drowsiness; fatigue; flushing; headache; hypotension; nausea; palpitations; peripheral oedema; skin reactions; tachycardia; vomiting Uncommon Angioedema; depression; erectile dysfunction; gingival hyperplasia; myalgia; paraesthesia; syncope Overdose Features of calcium-channel blocker poisoning include nausea, vomiting, dizziness, agitation, confusion, and coma in severe poisoning. Metabolic acidosis and hyperglycaemia may occur. In overdose, the dihydropyridine calcium-channel blockers cause severe hypotension secondary to profound peripheral vasodilatation. For details on the management of poisoning, see Calcium-channel blockers, under Emergency treatment of poisoning. Side-effects For diltiazem hydrochloride Common or very common Cardiac conduction disorders; constipation; gastrointestinal discomfort; malaise Uncommon Arrhythmias; diarrhoea; insomnia; nervousness Rare or very rare Dry mouth Frequency not known Asthma exacerbated; bronchospasm; cardiac arrest; congestive heart failure; extrapyramidal symptoms; fever; gynaecomastia; hepatitis; hyperglycaemia; hyperhidrosis; lupus-like syndrome; mood altered; photosensitivity reaction; severe cutaneous adverse reactions (SCARs); thrombocytopenia; vasculitis Side-effects, further information Systemic absorption following rectal use is unknown, therefore consider the possibility of side-effects listed for oral use. Overdose With oral use In overdose, diltiazem has a profound cardiac depressant effect causing hypotension and arrhythmias, including complete heart block and asystole.
Interactions
**Severe interactions:**
- Benzodiazepines (midazolam): Diltiazem significantly increases plasma concentrations of midazolam and prolongs its half-life.
- Statins (simvastatin, atorvastatin): Diltiazem is an inhibitor of CYP3A4 and has been shown to significantly increase the AUC of some statins.
**Other interactions (26):**
- Lomitapide Diltiazem (a moderate CYP3A4 inhibitor) may increase lomitapide plasma concentrations through CYP3A4 inhibition leading to increased risk of elevations in liver enzymes (see section 4.3).
- Concomitant use requiring caution: Lithium: Risk of increase in lithium-induced neurotoxicity.
- Theophylline: Increase in circulating theophylline levels.
- Amiodarone, digoxin: Increased risk of bradycardia: Caution is required when these are combined with diltiazem, particularly in elderly subjects and when high doses are used.
- Diltiazem hydrochloride may cause small increases in plasma levels of digoxin, requiring careful monitoring of AV conduction.
- Beta-blockers: Possibility of rhythm disturbances (pronounced bradycardia, sinus arrest), sino-atrial and atrio-ventricular conduction disturbances and heart failure (synergistic effect).
Pregnancy
With systemic use: Avoid.
Breast feeding
With systemic use: Significant amount present in milk-no evidence of harm but avoid unless no safer alternative.
Hepatic impairment
For all calcium-channel blockers In general, manufacturers advise caution (risk of increased exposure). Hepatic impairment For diltiazem hydrochloride Dose adjustments With systemic use: In general, manufacturers advise initial dose reduction to 60 mg twice daily (or 120 mg daily if using a once daily formulation), increased gradually as required. Hepatic impairment For Adizem-SR Capsules Dose adjustments Dose form not appropriate for initial dose titration. Hepatic impairment For Angitil SR Dose adjustments Dose form not appropriate for initial dose titration. Hepatic impairment For Angitil XL Dose adjustments Dose form not appropriate for initial dose titration. Hepatic impairment For Dilcardia SR Dose adjustments Dose form not appropriate for initial titration; manufacturer advises maximum 90 mg twice daily in hypertension. Hepatic impairment For Tildiem Retard Dose adjustments For treatment of angina , dose form not appropriate for initial titration; manufacturer advises maximum 120 mg twice daily. For mild to moderate hypertension , manufacturer advises initial dose reduction to 120 mg once daily; maximum 120 mg twice daily. Hepatic impairment For Tildiem LA Dose adjustments Manufacturer advises initial dose 200 mg daily; maximum 300 mg daily.
Renal impairment
Dose adjustments With systemic use: In general, manufacturers advise initial dose 60 mg twice daily (or 120 mg daily if using a once daily formulation), increased gradually as required (risk of increased exposure). Renal impairment For Adizem-SR Capsules Dose adjustments Dose form not appropriate for initial dose titration. Renal impairment For Angitil SR Dose adjustments Dose form not appropriate for initial dose titration. Renal impairment For Angitil XL Dose adjustments Dose form not appropriate for initial dose titration. Renal impairment For Dilcardia SR Dose adjustments Dose form not appropriate for initial titration; manufacturer advises max. dose 90 mg twice daily in hypertension. Renal impairment For Tildiem Retard Dose adjustments For mild to moderate hypertension , manufacturer advises initial dose 120 mg once daily; max. dose 120 mg twice daily. For treatment of angina , dose form not appropriate for initial titration; manufacturer advises max. dose 120 mg twice daily. Renal impairment For Tildiem LA Dose adjustments Manufacturer advises initial dose 200 mg daily; max. dose 300 mg daily.
Medicinal forms
Solution,Tablet,Capsule
Clinical governance
**Author:** MedNext Clinical Team. **Clinical reviewer:** Dr Shameer Deen, MBBS, MS, MRCS. **Sources:** BNF, Indian Pharmacopoeia, CIMS India. **Correction:** Report errors at support@mednext.academy.
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