Amlodipine Besylate

Calcium Channel Blocker Dihydropyridine Calcium Channel Antagonist

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 0.05-0.2 mg/kg (up to 0.5 mg/kg in some cases) q24h Duration: Long-term, adjust based on blood pressure monitoring
Notes: Start at low end and titrate upward every 2-4 weeks based on blood pressure response. Maximum dose reported up to 1.5 mg/kg/day in some refractory cases.
Cat PO 0.625-1.25 mg/cat (approximately 0.1-0.2 mg/kg) q24h Duration: Long-term, adjust based on blood pressure monitoring
Notes: Common starting dose is 0.625 mg/cat once daily. May increase to 1.25 mg/cat after 2-4 weeks if needed. Maximum dose reported up to 2.5 mg/cat/day.
Rabbit PO 0.2-0.5 mg/kg q24h Duration: As needed
Notes: Limited data; use with caution and monitor blood pressure.

Clinical Indications & Species Uses

General Indications
  • Treatment of systemic hypertension in small animals
Dog (Canine)
  • Systemic hypertension (primary or secondary to renal disease, hyperadrenocorticism, diabetes mellitus, etc.)
  • Management of congestive heart failure (off-label, as adjunctive therapy)
Cat (Feline)
  • Systemic hypertension (especially associated with chronic kidney disease, hyperthyroidism, or primary hypertension)
  • Management of hypertensive retinopathy and neurologic signs
Rabbit & Small Mammals
  • Occasionally used for hypertension, but not well-established

Pharmacology & Mechanism of Action

Drug Class: Calcium Channel Blocker | Pharmacological Group: Dihydropyridine Calcium Channel Antagonist

Mechanism of Action: Amlodipine is a dihydropyridine calcium channel blocker that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. It selectively binds to L-type calcium channels in the vascular smooth muscle, causing vasodilation of peripheral arterioles and reducing peripheral vascular resistance. This leads to a decrease in blood pressure. Unlike verapamil and diltiazem, amlodipine has minimal negative inotropic and chronotropic effects on the heart, making it particularly useful for treating hypertension without significantly affecting cardiac contractility or conduction. It also has a gradual onset of action and a long duration of effect due to its high affinity for calcium channels and slow dissociation from the receptor.

Pharmacodynamics: Amlodipine produces a dose-dependent reduction in systemic blood pressure by relaxing vascular smooth muscle. It also causes mild natriuresis and increases renal blood flow and glomerular filtration rate in some species. In cats with chronic kidney disease, amlodipine reduces systemic hypertension, which may slow the progression of renal damage. It does not affect cardiac output significantly at therapeutic doses. The drug also has anti-atherosclerotic and anti-platelet effects in some species, though these are not primary clinical uses in veterinary medicine.

⚡ Pharmacokinetics Summary

Absorption: Amlodipine is well absorbed after oral administration in most species. In dogs, oral bioavailability is approximately 88-100%. In cats, absorption is also good, with peak plasma concentrations occurring within 3-6 hours after oral dosing. Food does not significantly affect absorption.
Distribution: Amlodipine is extensively distributed throughout the body, with a large volume of distribution. It is highly lipophilic and binds to tissues, particularly vascular smooth muscle. It crosses the blood-brain barrier to a limited extent. In dogs, the volume of distribution is approximately 21 L/kg. It is also distributed into milk in lactating animals.
Metabolism: Amlodipine is extensively metabolized in the liver via cytochrome P450 enzymes, primarily CYP3A4, to inactive metabolites. In dogs, the major metabolite is the pyridine derivative. Hepatic metabolism results in a long elimination half-life.
Excretion: Amlodipine and its metabolites are excreted primarily in the urine (about 60%) and feces (about 20-25%). In dogs, approximately 10% of the drug is excreted unchanged in the urine. The elimination half-life is long, allowing once-daily dosing.
Half-Life: Dogs: 30-50 hours; Cats: 40-60 hours; Humans: 30-50 hours
Bioavailability: Oral bioavailability is high: Dogs ~88-100%, Cats ~100% (based on studies).
Protein Binding: Approximately 93-98% protein-bound in dogs and cats, primarily to albumin.

Available Formulations & Strengths

Oral Tablet 2.5 mg, 5 mg, 10 mg (PO)
Oral Solution (compounded) Various (e.g., 1 mg/mL) (PO)

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to amlodipine or other dihydropyridines
  • Severe hypotension
  • Cardiogenic shock
  • Severe aortic stenosis (may worsen symptoms)
  • Use with caution in animals with hepatic impairment (reduce dose)
Warnings & Clinical Precautions:
  • Use with caution in animals with congestive heart failure, especially if they are also receiving beta-blockers (risk of excessive hypotension).
  • Monitor blood pressure regularly during dose titration.
  • In cats with chronic kidney disease, amlodipine may cause a transient decrease in glomerular filtration rate; monitor renal parameters.
  • May cause reflex tachycardia in some animals, especially at high doses.
  • Safety in pregnant or lactating animals has not been established; use only when clearly needed.
  • Do not use in animals with known hypersensitivity to calcium channel blockers.
  • Use with caution in animals with hepatic disease; dose reduction may be necessary.
  • In food animals, withdrawal times must be observed; amlodipine is not approved for use in food animals.

Adverse Effects & Reactions

Common:

  • Gingival hyperplasia (especially in dogs)
  • Lethargy
  • Vomiting
  • Diarrhea
  • Anorexia
  • Mild hypotension

Serious / Severe:

  • Severe hypotension
  • Bradycardia or tachycardia
  • Syncope
  • Worsening of renal function
  • Hepatic enzyme elevations

Rare:

  • Peripheral edema
  • Skin reactions
  • Gastrointestinal ulceration
  • Blood dyscrasias

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Beta-blockers (e.g., atenolol, propranolol) Additive negative effects on cardiac conduction and contractility; may cause bradycardia, heart block, or heart failure. High
Other antihypertensives (e.g., ACE inhibitors, ARBs) Additive hypotensive effects; may cause excessive hypotension. Moderate
Cimetidine May increase amlodipine plasma levels by inhibiting CYP3A4 metabolism. Moderate
Cyclosporine Amlodipine may increase cyclosporine levels; monitor for toxicity. Moderate
Simvastatin Increased risk of myopathy and rhabdomyolysis. Moderate
Nitrates Enhanced hypotensive effect. Moderate

Overdose & Toxicity Management

Signs of Toxicity:

  • Severe hypotension
  • Bradycardia or tachycardia
  • Dizziness
  • Syncope
  • Lethargy
  • Nausea and vomiting
  • In severe cases, cardiovascular collapse and shock

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce emesis if recent ingestion and animal is conscious. Administer activated charcoal to reduce absorption. Monitor cardiovascular function closely. Administer intravenous fluids to maintain blood pressure. In severe cases, use calcium gluconate (0.5-1 mL/kg of 10% solution IV slowly) to reverse calcium channel blockade. Vasopressors (e.g., norepinephrine, dopamine) may be required. Atropine may be used for bradycardia. Provide supportive care as needed.

Food Animal Withdrawal Times

Amlodipine is not approved for use in food animals. If used off-label in food animals, a withdrawal time of at least 30 days for meat and 7 days for milk is recommended, but due to lack of data, a conservative approach is advised. Consult regulatory authorities.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (20-25°C, 68-77°F). Protect from light and moisture.

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Keep in a tightly closed container. Compounded oral solutions should be stored according to the compounding pharmacy's instructions, typically refrigerated and protected from light.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; approved for human use (Norvasc).

Extra-Label (Off-Label) Use: In the US, amlodipine is not FDA-approved for veterinary use; it is used extra-label under the Animal Medicinal Drug Use Clarification Act (AMDUCA). For food animals, extra-label use is prohibited unless a valid veterinarian-client-patient relationship exists and a withdrawal time is established. In the EU, similar regulations apply under the cascade.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Amlodipine is a first-line treatment for systemic hypertension in cats, particularly when associated with chronic kidney disease or hyperthyroidism. It is also used in dogs for hypertension. The drug is well-tolerated, with a long duration of action allowing once-daily dosing. Blood pressure should be measured before and during therapy to guide dosing. In cats, a common starting dose is 0.625 mg/cat once daily, with dose adjustments based on response. In dogs, start at 0.05-0.1 mg/kg once daily and titrate. Adverse effects are uncommon but may include gingival hyperplasia, especially in dogs. Use with caution in animals with hepatic impairment. Amlodipine is not approved for veterinary use, so informed consent and extra-label use considerations apply.

References & Literature

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