- USES: Tadalafil is used in the treatment of erectile dysfunction and for the signs and symptoms of benign prostatic hyperplasia. PHARMACOLOGY: Inhibition of cGMP specific phosphodiesterase type-5 (PDE5) in smooth muscle in the pulmonary vascular bed in the lungs and the corpus cavernosum of the penis. TOXICOLOGY: Similar to other phosphodiesterase 5 inhibitors, overdose is likely to cause excessive vasodilatation resulting in hypotension, tachycardia, headache, priapism, facial flushing, dizziness, and general weakness. EPIDEMIOLOGY: Poisoning is uncommon and rarely severe. OVERDOSE: Data limited. Following the administration of single doses up to 500 mg to healthy volunteers or multiple daily doses up to 100 mg to patients, adverse effects were similar to therapeutic doses. Intracerebral hemorrhage was associated with tadalafil (40 mg dose) misuse in an older adult; no permanent sequelae was reported. ADVERSE EVENTS: COMMON: Headache, back pain, dyspepsia, and myalgia are frequently reported. Other adverse effects that may occur include nasal congestion, flushing, and limb pain. RARE: The following have rarely been reported and a causal relationship of these events to tadalafil is uncertain: CARDIOVASCULAR: Angina pectoris, chest pain, hypotension, hypertension, myocardial infarction, postural hypotension, palpitations, syncope, and tachycardia can develop. GASTROINTESTINAL: Nausea, vomiting, diarrhea, dry mouth, dysphagia, esophagitis, gastroesophageal reflux, gastritis, epistaxis, pharyngitis, and upper abdominal pain have been observed. DERMATOLOGIC: Rash, pruritus, and increased sweating can occur. OTHER: Dyspnea, abnormal liver enzymes, changes in color vision, dizziness, hypesthesia, insomnia, paresthesia, somnolence, and vertigo can develop. DRUG INTERACTION: Severe hypotension may develop in patients taking tadalafil and nitrates.
Range of Toxicity:
- TOXICITY: Limited data. A toxic dose has not been established. Single doses of 500 mg and daily doses of 100 mg were well tolerated in healthy volunteers. THERAPEUTIC: ADULT: Initial dose: 10 mg orally no more than once daily; may increase to 20 mg or decrease to 5 mg, based on efficacy and tolerability; maximum: 20 mg daily. PEDIATRIC: Tadalafil is not indicated for use in pediatric patients
- Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Limited data. Tadalafil overdoses are likely to require only supportive care; there is no specific treatment. Treat headache, facial flushing, dizziness and general weakness with IV fluids. Hypotension and tachycardia are anticipated to be generally mild and well tolerated and usually respond to IV fluids. Infuse IV NaCL 10 to 20 mL/kg, as needed. MANAGEMENT OF SEVERE TOXICITY: Treatment is symptomatic and supportive. Reflex tachycardia is usually seen due to hypotension. Patients with persistent hypotension despite intravenous fluids require vasopressors, theoretically alpha agonists norepinephrine and phenylephrine may be more effective.
- Decontamination: PREHOSPITAL: Activated charcoal may be considered following a significant exposure, if the patient is able to protect their airway and IV fluids should be given for hypotension or reflex tachycardia. HOSPITAL: Activated charcoal may be considered following a significant exposure and the airway is protected. Significant toxicity is not anticipated following a minor exposure unless coingestants are involved.
- Contraindicated treatment: Hypotensive emergencies may result from the combination of tadalafil and nitrates, which include but are not limited to: nitroglycerin, isosorbide dinitrate, nitroprusside, amyl nitrite (also a recreational drug), and nitric oxide. Nitrates are CONTRAINDICATED in patients who ingested tadalafil within the past 24 hours due to the possibility of a severe hypotensive reaction. Nitrates should be also be avoided for 24 hours if myocardial ischemia is evident (longer if receiving P450 inhibitors or if hepatic or renal dysfunction are present), given the risk of hypotension and exacerbation of ischemia.
- Airway management: It is unlikely that a patient with an isolated tadalafil overdose will require airway management. Perform airway management early in patients that develop significant intoxication.
- Antidote: No specific antidote for tadalafil exists. IV fluids and peripheral vasopressors are the primary treatment of choice.
- Priapism: An immediate urological consult is necessary. Clinical history should include the use of other agents (ie, antihypertensives, antidepressants, illegal agents) that may also be contributing to priapism. In a patient with ischemic priapism the corpora cavernosa are often completely rigid and the patient complains of pain, while nonischemic priapism the corpora are typically tumescent, but not completely rigid and pain is not typical. Aspirate blood from the corpus cavernosum with a fine needle. Blood gas testing of the aspirated blood may be used to distinguish ischemic (typically PO2 less than 30 mmHg, PCO2 greater than 60 mmHg, and pH less than 7.25) and nonischemic priapism. Color duplex ultrasonography may also be useful. If priapism persists after aspiration, inject a sympathomimetic. PHENYLEPHRINE: Dose: Adult: For intracavernous injection, dilute phenylephrine with normal saline for a concentration of 100 to 500 mcg/mL and give 1 mL injections every 3 to 5 minutes for approximately 1 hour (before deciding that treatment is not successful). For children and patients with cardiovascular disease: Use lower concentrations in smaller volumes. NOTE: Treatment is less likely to be effective if done more than 48 hours after the development of priapism. Distal shunting (NOT first-line therapy) should only be considered after a trial of intracavernous injection of sympathomimetics.
- Seizure: Unlikely, but can be due to cerebral ischemia. Correct hypotension and treat with benzodiazepines.
- Monitoring of patient: Monitor vital signs and mental status in symptomatic patients. No specific lab work (CBC, electrolyte, urinalysis) is needed in most patients, unless otherwise clinically indicated. Tadalafil plasma levels are not clinically useful or readily available. Obtain an ECG and institute continuous cardiac monitoring in patients with moderate to severe toxicity (ie, tachycardia, hypotension).
- Enhanced elimination procedure: Tadalafil is highly protein bound and has a large volume of distribution; hemodialysis and hemoperfusion are not expected to be of benefit in overdose.
- Patient disposition: HOME CRITERIA: Asymptomatic children (other than mild drowsiness) with a small ingestion (1 tablet) and asymptomatic adults who have inadvertently ingested an extra dose may be managed at home. OBSERVATION CRITERIA: Symptomatic patients, those with deliberate ingestions or children with significant ingestions should be referred to a healthcare facility for observation for a minimum of 6 to 8 hours. ADMISSION CRITERIA: Patients with significant persistent abnormal vital signs such as hypotension and tachycardia should be admitted. Patients with severe symptoms (ie, coma, dysrhythmias, or evidence of end-organ damage) should be admitted to an intensive care setting. CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity (ie, dysrhythmias, severe hypotension, coma) or in whom the diagnosis is not clear.