Papaverine: Medical Use and Dosing
Primary Clinical Applications
Papaverine is primarily used in two distinct clinical contexts: (1) intra-arterial administration for cerebral vasospasm following subarachnoid hemorrhage, and (2) intracavernous injection for erectile dysfunction. 1
Cerebral Vasospasm After Subarachnoid Hemorrhage
Indication and Role
- Selective intra-arterial vasodilator therapy may be reasonable for symptomatic cerebral vasospasm after aneurysmal SAH, either after, together with, or in place of triple-H therapy (Class IIb, Level of Evidence B). 1
- Papaverine is specifically used for distal cerebral vessels (third- and fourth-order) that cannot be treated with balloon angioplasty. 1
- Balloon angioplasty is superior to papaverine in terms of durability and efficacy for accessible vessels, but papaverine remains useful for small vessel pathology. 1
Dosing Protocol for Cerebral Vasospasm
- Concentration: 3 mg/mL 1
- Infusion rate: 6 to 9 mL/min 1
- Maximum dose: Up to 300 mg per vascular territory 1
- Delivery method: Superselective slow infusion via microcatheter directly into or just proximal to the spastic vessels 1, 2
Critical Monitoring Requirements
- Intracranial pressure must be monitored during infusion, as elevated ICP is the major complication associated with papaverine. 1
- Other physiological and neurophysiological parameters should be continuously monitored. 1
- ICP elevation can be controlled with brief hyperventilation, mannitol, barbiturate therapy, and/or ventricular drainage. 1
Safety Profile and Complications
- Serious complication rates range from 2% to 5%. 1
- Superselective slow infusion has reduced risks compared to earlier delivery methods, which included brainstem depression, hypotension, aggravation of vasospasm, seizures, respiratory arrest, transient hemiparesis, and elevated intracranial pressure. 1
- Papaverine is now used less frequently than other vasodilators (particularly verapamil and other calcium channel blockers) because it can produce neurotoxicity. 1
- The primary limitation is short duration of benefit. 1
Evidence Quality
- Papaverine demonstrates angiographic reversal of cerebral vasospasm, but there is no correlation to severity of spasm, timing of intervention, or papaverine dose in terms of clinical outcomes. 1
- Early therapy (performed within 2 hours) may be advantageous for sustained clinical improvement. 1
Erectile Dysfunction
Indication and Role
- Intracavernous injection therapy is the most effective non-surgical treatment for ED, with papaverine being one of the most widely used vasoactive drugs. 1
- Papaverine is used as monotherapy or in combination therapy (bimix: papaverine + phentolamine; trimix: papaverine + phentolamine + alprostadil). 1
- Only alprostadil is FDA-approved for intracavernous injection in the U.S.; papaverine is used off-label, typically in combination formulations. 1
Administration Protocol
- The initial trial dose must be administered under healthcare provider supervision. 1
- Healthcare providers must instruct patients on proper injection technique, determine effective dose, and monitor for side effects, especially prolonged erection. 1
- Intracavernous injection therapy should not be used more than once in a 24-hour period. 1
- An in-office injection test should be performed before prescribing ICI therapy. 1
Dosing for Erectile Dysfunction
- Doses range from 15 to 80 mg for intracavernous self-injection. 3
- If 80 mg papaverine alone is insufficient, phentolamine may be added. 3
- Dose adjustment is necessary based on individual response and risk factors. 4
Risk Factors for Priapism
- Younger men with better baseline erectile function have significantly higher risk of priapism (p < 0.0001 and p < 0.023, respectively). 4
- Patients with overt neurological disease have increased priapism rates despite lower doses. 4
- Patients with psychogenic or neurogenic impotence have much greater risk than those with vasculogenic impotence (p < 0.001). 4
- Patients with coronary artery disease have significantly lower risk (p < 0.05). 4
- However, all impotent patients are potentially at risk for pharmacologically induced priapism, regardless of etiology. 4
Critical Safety Counseling
- Physicians must inform patients of the potential for prolonged erections, have a plan for urgent treatment of prolonged erections, and inform the patient of this plan. 1
- Priapism is the most serious potential complication of papaverine use for ED. 4
- Other complications include fibrous plaques (occurred in 2 of 33 patients in one series), ecchymoses, and urethral bleeding. 3, 5
Efficacy Considerations
- Sexual stimulation is very important and results in varying erections on consecutive occasions with the same papaverine dose. 3
- Patients with severe vasculogenic disease and penile-brachial pressure index less than 0.65 are not good candidates for papaverine therapy. 5
- In one study, 55% of patients were satisfied with the method, but 36% stopped injections for various reasons. 3
General Parenteral Administration (Non-Specific Indications)
FDA-Approved Dosing
- Papaverine hydrochloride may be administered intravenously or intramuscularly. 6
- Intravenous route is recommended when immediate effect is desired, but must be injected slowly over 1 to 2 minutes to avoid uncomfortable or alarming side effects. 6
- Dosage: 1 to 4 mL repeated every 3 hours as indicated. 6
- For cardiac extrasystoles: 2 doses may be given 10 minutes apart. 6
Important Clinical Pitfalls
Common Errors to Avoid
- Do not use rapid intravenous injection—always administer slowly over 1-2 minutes to prevent adverse effects. 6
- Do not proceed with intracavernous injection therapy without proper in-office testing and patient education. 1
- Do not assume all ED patients respond similarly—adjust initial dosing based on age, baseline erectile function, and etiology of impotence. 4
- Do not use papaverine as first-line for cerebral vasospasm in accessible vessels—balloon angioplasty is superior for durability and efficacy. 1