Diltiazem Hydrochloride

Calcium Channel Blocker (Non-dihydropyridine) Benzothiazepine derivative

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 0.5-1.5 mg/kg (immediate-release) q8h Duration: Variable, depending on response
Notes: For atrial fibrillation, start at 0.5 mg/kg q8h and titrate to effect. Extended-release: 10-20 mg/kg q24h (or 30-60 mg/dog q24h).
Dog IV 0.1-0.2 mg/kg (slow bolus over 2-3 minutes) q8h as needed Duration: For acute rate control
Notes: Monitor ECG and blood pressure. May be followed by a CRI of 2-6 mcg/kg/min.
Cat PO 1-2.5 mg/kg (immediate-release) q8h Duration: Variable
Notes: For HCM, start at 1 mg/kg q8h and titrate. Extended-release: 10 mg/kg q24h (or 30 mg/cat q24h).
Cat IV 0.1-0.2 mg/kg (slow bolus over 2-3 minutes) q8h as needed Duration: For acute rate control
Notes: Use with caution in cats with HCM; monitor for hypotension.
Horse PO 0.5-1.5 mg/kg q8h Duration: Variable
Notes: For atrial fibrillation, may be used as an alternative to quinidine. Monitor heart rate and rhythm.
Horse IV 0.05-0.1 mg/kg (slow bolus) q8h as needed Duration: For acute rate control
Notes: Use with caution; may cause hypotension.
Rabbit PO 0.5-2 mg/kg q8-12h Duration: Variable
Notes: Limited data; use with caution.

Clinical Indications & Species Uses

General Indications
  • Rate control in supraventricular tachyarrhythmias
  • Hypertension
  • Hypertrophic cardiomyopathy (especially in cats)
Dog (Canine)
  • Supraventricular tachyarrhythmias (atrial fibrillation, atrial flutter, supraventricular tachycardia)
  • Hypertension (especially systemic hypertension)
  • Hypertrophic cardiomyopathy (adjunctive therapy for rate control)
Cat (Feline)
  • Hypertrophic cardiomyopathy (HCM) for rate control and diastolic dysfunction
  • Supraventricular tachyarrhythmias
  • Systemic hypertension (especially when beta-blockers are contraindicated)
Horse (Equine)
  • Supraventricular tachyarrhythmias (atrial fibrillation, atrial flutter)
  • Hypertension (rarely used)
Rabbit & Small Mammals
  • Hypertension (occasionally used)
  • Cardiac disease (adjunctive therapy)
Exotic & Other Species
  • Hypertension in some exotic species (e.g., ferrets, reptiles) - limited evidence

Pharmacology & Mechanism of Action

Drug Class: Calcium Channel Blocker (Non-dihydropyridine) | Pharmacological Group: Benzothiazepine derivative

Mechanism of Action: Diltiazem inhibits the influx of calcium ions through L-type calcium channels in cardiac and vascular smooth muscle. This reduces intracellular calcium concentration, leading to vasodilation of peripheral arterioles, decreased myocardial contractility (negative inotropic effect), and decreased heart rate (negative chronotropic effect) by slowing conduction through the sinoatrial (SA) and atrioventricular (AV) nodes. It also reduces myocardial oxygen demand and has antiarrhythmic properties, particularly for supraventricular tachyarrhythmias.

Pharmacodynamics: Diltiazem produces dose-dependent decreases in heart rate, blood pressure, and myocardial contractility. It prolongs the effective refractory period of the AV node and slows AV conduction, making it effective for rate control in atrial fibrillation and flutter. It also causes coronary vasodilation, improving myocardial oxygen supply. In animals, it is used primarily for its antiarrhythmic and antihypertensive effects.

⚡ Pharmacokinetics Summary

Absorption: Rapidly absorbed after oral administration, but undergoes extensive first-pass metabolism, resulting in variable bioavailability. Peak plasma concentrations occur within 1-2 hours for immediate-release formulations. Extended-release formulations provide more sustained absorption.
Distribution: Widely distributed throughout the body. It crosses the blood-brain barrier and placenta. Volume of distribution is approximately 3-5 L/kg in dogs. Protein binding is approximately 70-80% in dogs and cats.
Metabolism: Extensively metabolized in the liver by cytochrome P450 enzymes (primarily CYP3A4) to active and inactive metabolites. The primary active metabolite is desacetyldiltiazem, which has about 25-50% of the parent drug's potency.
Excretion: Eliminated primarily in the urine as metabolites, with a small amount excreted in feces. Less than 4% of the drug is excreted unchanged in the urine.
Half-Life: Dogs: approximately 2-3 hours (immediate-release), 5-7 hours (extended-release). Cats: approximately 2-4 hours. Horses: approximately 1-2 hours.
Bioavailability: Oral bioavailability is approximately 40% in dogs and 30% in cats due to first-pass metabolism. Intravenous administration provides 100% bioavailability.
Protein Binding: 70-80% in dogs and cats

Available Formulations & Strengths

Oral Tablet (immediate-release) 30 mg, 60 mg, 90 mg, 120 mg (PO)
Oral Capsule (extended-release) 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, 420 mg (PO)
Injectable Solution 5 mg/mL (5 mL vial) (IV)

Contraindications & Clinical Warnings

Contraindications:
  • Known hypersensitivity to diltiazem
  • Severe hypotension (systolic BP < 90 mmHg)
  • Cardiogenic shock
  • Second- or third-degree AV block without a functioning pacemaker
  • Sick sinus syndrome
  • Severe congestive heart failure (unless caused by tachyarrhythmia)
  • Concurrent use with IV beta-blockers (risk of severe bradycardia and asystole)
Warnings & Clinical Precautions:
  • Use with caution in animals with impaired hepatic or renal function
  • May exacerbate heart failure in animals with poor myocardial function
  • Use with caution in animals with pre-existing hypotension
  • In cats, use with caution in those with dynamic outflow tract obstruction (may worsen obstruction)
  • Monitor ECG and blood pressure during IV administration
  • Do not crush or split extended-release formulations
  • Abrupt withdrawal may cause rebound hypertension or arrhythmias
  • Use with caution in animals with myasthenia gravis (may worsen muscle weakness)

Adverse Effects & Reactions

Common:

  • Hypotension
  • Bradycardia
  • Gastrointestinal upset (vomiting, diarrhea)
  • Anorexia
  • Lethargy

Serious / Severe:

  • Severe bradycardia or AV block
  • Worsening of heart failure
  • Hepatic toxicity (rare)
  • Severe hypotension leading to collapse

Rare:

  • Gingival hyperplasia (with chronic use)
  • Skin reactions
  • Peripheral edema
  • Elevated liver enzymes

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Beta-blockers (e.g., propranolol, atenolol) Additive negative chronotropic and inotropic effects; risk of severe bradycardia, AV block, and heart failure High
Digoxin Diltiazem may increase digoxin levels by 20-50%, increasing risk of digoxin toxicity Moderate
CYP3A4 inhibitors (e.g., ketoconazole, erythromycin) May increase diltiazem plasma concentrations, leading to toxicity Moderate
CYP3A4 inducers (e.g., phenobarbital, rifampin) May decrease diltiazem plasma concentrations, reducing efficacy Moderate
Inhalational anesthetics (e.g., isoflurane) Additive hypotensive and negative inotropic effects Moderate
Furosemide May increase risk of hypotension and electrolyte imbalances Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Severe hypotension
  • Bradycardia
  • AV block
  • Cardiac arrest
  • Lethargy
  • Confusion
  • Nausea and vomiting

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Administer IV fluids for hypotension. Atropine or dopamine may be used for bradycardia. Calcium gluconate (10% solution, 0.5-1 mL/kg IV slowly) may be given to counteract calcium channel blockade. In severe cases, temporary cardiac pacing may be required. Activated charcoal may be considered if ingestion was recent. Monitor ECG and blood pressure closely.

Food Animal Withdrawal Times

Not approved for food animals; no withdrawal times established. Use in food animals is off-label and requires veterinary oversight. A withdrawal period of at least 7 days for meat and 72 hours for milk is often recommended, but consult regulatory guidelines.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (20-25°C, 68-77°F)

Handling & Special Conditions: Protect from moisture. Keep in tightly closed container. Do not freeze injectable solution.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Approved for human use; not specifically approved for veterinary use, but commonly used off-label in veterinary medicine.

Extra-Label (Off-Label) Use: In the US, extra-label use in food animals is permitted under AMDUCA with a valid veterinary-client-patient relationship, but requires extended withdrawal times. Not approved for use in food animals.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Diltiazem is a valuable drug for managing supraventricular tachyarrhythmias and hypertension in small animals, particularly cats with hypertrophic cardiomyopathy. It is often preferred over beta-blockers in cats with HCM because it also improves diastolic function. However, its use requires careful monitoring of heart rate and blood pressure, especially during IV administration. Extended-release formulations improve owner compliance but must not be crushed. In dogs, it is commonly used for atrial fibrillation, but may be less effective than digoxin for rate control in some cases. Always titrate doses to effect and monitor for adverse effects. In emergency situations, IV diltiazem is effective for rapid rate control, but should be used with caution in animals with compromised cardiac function. Drug interactions, especially with beta-blockers, should be considered. For food animals, diltiazem is not commonly used and withdrawal times are not established.

References & Literature

  • 📚 Plumb's Veterinary Drug Handbook
  • 📚 Papich Veterinary Pharmacology and Therapeutics
  • 📚 Compendium of Veterinary Products (CVP)