Tadalafil

Phosphodiesterase-5 (PDE5) inhibitor Vasodilator, Urogenital smooth muscle relaxant

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 1 mg/kg (for pulmonary hypertension) or 0.5-1 mg/kg (for urinary incontinence) q24h (once daily) Duration: Long-term, as needed
Notes: For pulmonary hypertension, start at 1 mg/kg once daily; may increase to 2 mg/kg if needed. For USMI, use 0.5-1 mg/kg once daily. Administer with or without food.
Cat PO 1 mg/kg q24h Duration: As needed for urethral spasm or pulmonary hypertension
Notes: Use cautiously in cats with renal impairment. Monitor for hypotension.
Horse PO 1-2 mg/kg q24h Duration: Variable, based on response
Notes: Limited data; use with caution. May be used for EIPH prevention in racehorses (off-label).

Clinical Indications & Species Uses

General Indications
  • Pulmonary hypertension
  • Urethral relaxation for urinary obstruction
  • Smooth muscle relaxation in urogenital tract
Dog (Canine)
  • Pulmonary hypertension (primary or secondary)
  • Congestive heart failure (adjunctive therapy)
  • Urethral sphincter mechanism incompetence (USMI) causing urinary incontinence
  • Benign prostatic hyperplasia (BPH) to reduce prostatic smooth muscle tone
  • Urethral obstruction (as an adjunct to relieve urethral spasm)
Cat (Feline)
  • Pulmonary hypertension (less common)
  • Urethral obstruction (adjunctive therapy to relieve urethral spasm)
  • Feline lower urinary tract disease (FLUTD) with urethral spasm
Horse (Equine)
  • Pulmonary hypertension (rarely used)
  • Erectile dysfunction (in breeding stallions, off-label)
  • Exercise-induced pulmonary hemorrhage (EIPH) – investigational

Pharmacology & Mechanism of Action

Drug Class: Phosphodiesterase-5 (PDE5) inhibitor | Pharmacological Group: Vasodilator, Urogenital smooth muscle relaxant

Mechanism of Action: Tadalafil selectively inhibits phosphodiesterase type 5 (PDE5), the enzyme responsible for the degradation of cyclic guanosine monophosphate (cGMP) in smooth muscle cells. By preventing cGMP breakdown, tadalafil enhances nitric oxide (NO)-mediated vasodilation and relaxation of smooth muscle in the corpus cavernosum, pulmonary vasculature, and other tissues. In veterinary medicine, this results in improved blood flow and reduced smooth muscle tone in the urinary and reproductive tracts, as well as decreased pulmonary arterial pressure.

Pharmacodynamics: Tadalafil produces dose-dependent relaxation of vascular and non-vascular smooth muscle. In dogs, it reduces pulmonary arterial pressure and improves exercise tolerance in cases of pulmonary hypertension. It also relaxes urethral smooth muscle, decreasing urethral resistance and facilitating urine passage in cases of urethral obstruction or urinary incontinence. The drug has a longer duration of action compared to sildenafil, with effects lasting up to 24-36 hours in some species.

⚡ Pharmacokinetics Summary

Absorption: Tadalafil is well absorbed after oral administration. In dogs, peak plasma concentrations are reached within 1-2 hours. Food can delay absorption but does not significantly affect overall bioavailability.
Distribution: Tadalafil is widely distributed into tissues, with a large volume of distribution. It is highly bound to plasma proteins (approximately 94% in humans; similar in animals). It crosses the blood-brain barrier to a limited extent.
Metabolism: Tadalafil is primarily metabolized by the hepatic cytochrome P450 enzyme CYP3A4. Metabolites are largely inactive.
Excretion: Excretion is mainly via feces (approximately 61% of the dose) and urine (approximately 36% of the dose) as metabolites. The elimination half-life is prolonged compared to other PDE5 inhibitors.
Half-Life: Dogs: approximately 4-6 hours (oral); Horses: approximately 4-8 hours; Humans: 17.5 hours (for reference).
Bioavailability: Oral bioavailability is approximately 30-50% in dogs, with interindividual variability.
Protein Binding: Approximately 94% bound to plasma proteins.

Available Formulations & Strengths

Oral Tablet 2.5 mg, 5 mg, 10 mg, 20 mg (PO)
Oral Tablet (compounded) Various strengths (e.g., 5 mg, 10 mg, 20 mg) (PO)

Contraindications & Clinical Warnings

Contraindications:
  • Concurrent use with nitrates or nitric oxide donors (risk of severe hypotension)
  • Hypersensitivity to tadalafil or any component
  • Severe hepatic impairment
  • Severe hypotension (systolic blood pressure < 90 mmHg)
  • Concurrent use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole) without dose adjustment
Warnings & Clinical Precautions:
  • Use with caution in patients with cardiovascular disease, especially those with pre-existing hypotension or volume depletion.
  • Monitor blood pressure in patients at risk of hypotension.
  • Use with caution in patients with renal impairment; dose adjustment may be necessary.
  • Not recommended for use in pregnant or lactating animals unless clearly needed.
  • In horses, use with caution in performance animals due to potential for detection in drug testing.
  • Do not use in animals with known hypersensitivity to PDE5 inhibitors.

Adverse Effects & Reactions

Common:

  • Gastrointestinal upset (vomiting, diarrhea)
  • Facial flushing
  • Nasal congestion
  • Headache (in humans; may occur in animals)

Serious / Severe:

  • Hypotension
  • Priapism (prolonged erection in males)
  • Sudden hearing loss (rare)
  • Cardiovascular collapse (overdose)

Rare:

  • Seizures
  • Allergic reactions (angioedema)
  • Hepatotoxicity

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Nitrates (e.g., nitroglycerin, isosorbide) Additive hypotensive effect; severe hypotension can occur. High
CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, erythromycin) Increased tadalafil plasma concentrations; risk of toxicity. Moderate
Alpha-blockers (e.g., prazosin, doxazosin) Additive hypotensive effect. Moderate
Antihypertensives (e.g., ACE inhibitors, beta-blockers) Additive hypotensive effect. Moderate
CYP3A4 inducers (e.g., rifampin, phenobarbital) Decreased tadalafil efficacy. Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Severe hypotension
  • Tachycardia
  • Flushing
  • Gastrointestinal distress
  • Priapism (in males)

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce emesis if recent ingestion and animal is conscious. Administer activated charcoal to reduce absorption. Provide intravenous fluids and vasopressors (e.g., dopamine, norepinephrine) to maintain blood pressure. Monitor cardiac function and blood pressure closely. There is no specific antidote.

Food Animal Withdrawal Times

Not approved for use in food animals. Withdrawal times are not established. Do not use in animals intended for human consumption.

Storage, Handling & Regulatory Information

Storage Temperature: Store at controlled room temperature 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F).

Handling & Special Conditions: Protect from moisture. Keep in original container.

Dispensing Status: Prescription Required (Rx Only)

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

Extra-Label (Off-Label) Use: In the US, tadalafil is not FDA-approved for veterinary use; however, it can be prescribed legally under the Animal Medicinal Drug Use Clarification Act (AMDUCA) for extra-label use in animals, provided a valid veterinarian-client-patient relationship exists and appropriate withdrawal times are considered for food animals.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Tadalafil is a valuable therapeutic option for managing pulmonary hypertension in dogs, particularly when sildenafil is not tolerated or requires more frequent dosing. Its long duration of action allows once-daily dosing, improving owner compliance. In cases of urethral obstruction or urinary incontinence, tadalafil can be used as an adjunct to relax urethral smooth muscle. However, its use in cats is less established and requires careful monitoring for adverse effects. Always assess cardiovascular status before initiating therapy, and monitor blood pressure during treatment. Due to potential drug interactions, review the patient's medication list thoroughly. In performance animals, be aware of potential regulatory restrictions. For food animals, tadalafil is not recommended due to lack of withdrawal data.

References & Literature

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