Diltiazem for Hypertension, Angina, and Cardiac Rate Control

Diltiazem is a calcium channel blocker available in oral extended-release capsules and film-coated tablets, as well as an intravenous solution. It is primarily used to manage high blood pressure and chest pain due to angina, and to control certain heart rhythm disorders. Its extended-release forms provide once-daily dosing for hypertension and chronic stable angina, while the injectable form is used for rapid control of heart rate during arrhythmias.

Oral extended-release capsules: Used alone or with other antihypertensives to treat hypertension and for managing chronic stable angina.

Oral film-coated tablets: Indicated for management of chronic stable angina and angina due to coronary artery spasm.

Intravenous injection: Used in adults for temporary control of rapid ventricular rate in atrial fibrillation or atrial flutter and for rapid conversion of paroxysmal supraventricular tachycardias (PSVT) to sinus rhythm.

Diltiazem hydrochloride

Diltiazem blocks calcium ions from entering heart and blood vessel muscle cells during electrical stimulation, which relaxes vascular smooth muscle and reduces peripheral resistance, helping lower blood pressure. It dilates coronary arteries, improving blood flow and reducing spasms responsible for angina. In arrhythmias, it slows conduction through the atrioventricular (AV) node, helping to control rapid heart rates.

Extended-release capsules (Hypertension and Angina): Initial doses typically start at 180 mg or 240 mg once daily, taken in the morning on an empty stomach as food can increase absorption. Dose may be adjusted between 120 mg and 540 mg daily depending on therapeutic response and tolerability. Capsules must be swallowed whole, not chewed or crushed.

Film-coated tablets (Angina): Start at 30 mg four times daily (before meals and at bedtime) and increase gradually every 1-2 days as needed. Average effective dose range is 180 to 360 mg per day given in divided doses. Tablets may be crushed or chewed if necessary, except 30 mg tablets are typically swallowed whole.

Intravenous injection (Arrhythmia control in adults only): Initial bolus dose of 0.25 mg/kg (about 20 mg over 2 minutes). If response is insufficient after 15 minutes, an additional dose of 0.35 mg/kg (around 25 mg over 2 minutes) may be given. Following bolus, begin continuous infusion at 5 mg/hour and titrate by 5 mg/hour increments up to 15 mg/hour based on response. Infusions should not exceed 24 hours, and continuous ECG and blood pressure monitoring are required. Do not mix with other drugs in the same IV line.

Diltiazem is contraindicated in patients with sick sinus syndrome without a pacemaker, second- or third-degree AV block without a pacemaker, hypotension (systolic BP under 90 mmHg), acute myocardial infarction with pulmonary congestion, hypersensitivity to diltiazem, ventricular tachycardia (for injection), atrial fibrillation or flutter with accessory bypass tracts (e.g., Wolff-Parkinson-White syndrome, for injection), and concomitant intravenous beta-blocker use (for injection).

Contraindications include: Sick sinus syndrome without a functioning pacemaker, second- or third-degree AV block without pacemaker, severe hypotension (systolic BP

Serious risks and precautions: Diltiazem can slow AV nodal conduction and may precipitate bradycardia or AV block, especially when combined with beta-blockers or digitalis. It may worsen heart failure, particularly in patients with preexisting impaired ventricular function. Monitor for symptomatic hypotension. Acute hepatic injury has rarely occurred; liver enzymes should be monitored during therapy. Use caution in patients with hepatic or renal impairment. Diltiazem injection may cause hemodynamic deterioration and ventricular fibrillation if used incorrectly in tachyarrhythmias of ventricular origin; proper diagnosis is essential before administration. Continuous ECG and blood pressure monitoring required during IV use.

Common side effects with oral extended-release capsules (≥1% incidence): Rhinitis, headache, pharyngitis, constipation, increased cough, flu syndrome, peripheral edema, myalgia, diarrhea, vomiting, sinusitis, asthenia, back pain, nausea, dyspepsia, vasodilatation, abdominal pain, arthrosis, insomnia, dyspnea, rash, tinnitus.

Common side effects with oral tablets: Edema, headache, nausea, dizziness, rash, asthenia.

Injection common effects (≥1%): Hypotension, injection site reactions (itching, burning), flushing (vasodilation), arrhythmias (junctional rhythm or isorhythmic dissociation).

Less frequent but serious postmarketing reports: Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, angioedema, erythema multiforme, and other serious dermatologic reactions.

Diltiazem interacts with multiple drugs affecting cardiac conduction or metabolism:

• Beta-blockers and digitalis: May produce additive effects on AV conduction leading to bradycardia or AV block; dose adjustments and monitoring are necessary.
• Statins metabolized by CYP3A4 (e.g., simvastatin, lovastatin): Increased plasma concentrations increasing risk of myopathy or rhabdomyolysis. Dose limits and careful monitoring advised; use non-CYP3A4 statins if possible.
• Cytochrome P450 3A4 inhibitors (e.g., cimetidine, ketoconazole) and inducers (e.g., rifampin, carbamazepine): Can alter diltiazem levels; dose adjustments and monitoring recommended.
• Benzodiazepines (midazolam, triazolam): Increased sedation due to increased drug levels.
• Carbamazepine: Increased carbamazepine levels; monitor for toxicity.
• Clonidine: Increased risk of bradycardia; monitor heart rate.
• Ivabradine: Avoid concurrent use due to risk of exacerbated bradycardia and conduction disturbances.
• Quinidine: Increased quinidine levels; monitor and adjust dose accordingly.
• Ranolazine: Limit dose to 500 mg twice daily when given with diltiazem.
• Anesthetics: Potentiated cardiac depression and vascular dilation; careful titration required.

Pregnancy: Available data from decades of use in humans have not shown an increased risk of major birth defects or adverse pregnancy outcomes. Animal studies at doses significantly higher than human therapeutic levels showed embryo-fetal lethality and skeletal abnormalities. The background risk of birth defects and miscarriage in the general population is 2-4% and 15-20%, respectively.

Lactation: Diltiazem is present in human milk at concentrations approximating serum levels. Effects on the breastfed infant are unknown. Consider benefits of breastfeeding alongside the mother's need for diltiazem and potential infant risks.

In case of overdose, provide appropriate supportive care and monitoring. Diltiazem is not effectively removed by dialysis. Limited evidence suggests plasmapheresis may hasten elimination. Toxic dose in humans is unknown. Signs of overdose may include severe hypotension, bradycardia, AV block, and heart failure symptoms.

Storage conditions are not explicitly stated in the supplied evidence.