Papaverine is a smooth muscle relaxant that has been available for over 60 years. It has been marketed for the relief of cerebral and peripheral ischemia conditions secondary to arterial spasm. These conditions include vascular spasm associated with acute myocardial infarction, angina pectoris, peripheral and pulmonary embolism, peripheral vascular disease with a vasospastic element, or certain cerebral angiospastic states; and visceral spasm causing ureteral, biliary, or gastrointestinal colic. In 1979, a Food and Drug Administration Advisory Committee evaluated studies on papaverine and concluded that there was a lack of objective data to support the therapeutic use of papaverine for these conditions. Papaverine remains available despite the committee's recommendation that it be withdrawn from the market.
Papaverine is currently used for many off-label indications. Injectable papaverine has been studied via intra-arterial, intrathecal, intraluminal, perivascular, and intercavernous routes. In patients with severe vasospasm following aneurysmal subarachnoid hemorrhage, papaverine can be injected directly into cerebral arteries to prevent the development of delayed ischemic neurologic deficits. Papaverine can also be used in these patients to facilitate dilation of cerebral vessels prior to balloon angioplasty. Intra-arterial injection of papaverine has also been successful for the treatment of non-occlusive mesenteric ischemia. In patients undergoing diagnostic cardiac catheterization, intracoronary papaverine can be used to evaluate coronary flow reserve. Because of the potential for adverse cardiac effects, alternate agents such as adenosine may be more appropriate in these settings. Intrathecal injection of papaverine into the cerebrospinal fluid prior to aortic cross-clamping can prevent spinal cord neurologic injury in patients undergoing thoracoabdominal aortic surgery. Papaverine has also been administered by topical application, intraluminal injection, or perivascular injection in patients undergoing venous and arterial graft harvesting. Papaverine has been shown to improve blood flow through grafted arteries and veins by preventing vasospasm. Intercavernous injections of papaverine, either alone or combined with phentolamine and/or alprostadil, have been widely used for the treatment of erectile dysfunction. According to ED treatment guidelines, oral phosphodiesterase type 5 inhibitors (PDE5 inhibitor) are considered first-line therapy. Second-line treatment options include intracavernous injection and intra-urethral therapy. Intracavernous injection therapy is the most effective nonsurgical treatment for ED, with predictable and sustained response. However, it is invasive and caries notable side-effects including priapism and penile fibrosis.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Papaverine may be administered without regard to meals.
Oral Solid Formulations
-Papaverine capsules should be swallowed whole; do not chew, open, break, or crush.
Injectable Administration
-Papaverine may be administered via the intramuscular, intravenous, intra-arterial*, intracoronary*, intracavernous*, or intrathecal* routes.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever the solution and container permit.
Intravenous Administration
-No dilution necessary.
-Inject papaverine IV into a peripheral vein over 1 to 2 minutes. Blood pressure should be monitored frequently.
Intramuscular Administration
-No dilution necessary.
-Inject papaverine deeply into a large muscle. Aspirate prior to injection to avoid injection into a blood vessel.
Intrathecal Administration
NOTE: intrathecal injections require preservative-free product.
NOTE: Intrathecal administration of papaverine requires specialized techniques. Only clinicians familiar with this method of administration and with management of potential complications should administer papaverine intrathecally.
-Dilute papaverine powder with the appropriate amount of 10% dextrose in water to make a 1% solution. This solution must be filtered using a 0.22 micron filter to produce a preservative-free solution for intrathecal injection.
Other Injectable Administration
Intracoronary administration*
NOTE: Intracoronary administration of papaverine requires specialized techniques. Only clinicians familiar with this method of administration and with management of potential complications should administer papaverine via this route.
-Dilute to a concentration of 1mg/ml in NS.
-Inject 8-12 mg over 10 seconds.
Intracavernous administration*
NOTE: Papaverine is not approved by the FDA for intercavernous administration.
-This administration method should only be prescribed by specially trained physicians. Patients should be trained and observed for appropriate self-administration technique prior to prescribing.
-No dilution necessary.
-After the appropriate papaverine dose has been drawn into the syringe, the head of the penis is held between the thumb and forefinger. The penis is stretched lengthwise along the thigh while sitting upright or slightly reclined. Position the needle of the syringe so that the drug will be injected as described by your prescriber. Follow the directions given to you by your prescriber. After injection, the syringe should be withdrawn. Apply pressure to the injection site with an alcohol swab for 5 minutes (or until bleeding stops). The injection site and side of the penis should be rotated to minimize local adverse effects related to repeated local injections.
Intra-arterial (superior mesenteric artery) infusion*
NOTE: Intra-arterial administration of papaverine requires specialized techniques. Only clinicians familiar with this method of administration and with management of potential complications should administer papaverine intra-arterially.
-Dilute to a concentration of 1mg/ml in NS.
-Infuse into the superior mesenteric artery using a controlled infusion device.
Intra-arterial (cerebral vasculature) infusion*
NOTE: Intra-arterial administration of papaverine requires specialized techniques. Only clinicians familiar with this method of administration and with management of potential complications should administer papaverine intra-arterially.
-Dilute to a concentration of 3mg/ml in NS.
-Infuse into the selected cerebral artery via a superselective catheter over 15-60 minutes using a controlled infusion device. Arterial and intracranial pressures should be continuously monitored.
Papaverine is reported to infrequently cause hepatitis that can rarely progress to cirrhosis. Hepatitis with elevated hepatic enzymes and abdominal pain has been documented with oral papaverine and elevated hepatic enzymes have also been noted following intracavernosal injection. Hepatotoxicity secondary to papaverine is believed to be immune mediated. There have also been case reports of chronic papaverine hepatotoxicity manifested by chronic active hepatitis and cirrhosis following long term treatment with oral papaverine. Histologic lesions suggest an immune mechanism is also responsible for chronic toxicity.
Other adverse effects associated with the use of papaverine include abdominal discomfort, anorexia, constipation, diarrhea, diaphoresis, intense flushing of the face, headache, hypertension, malaise, nausea, sinus tachycardia, increase in depth of respiration, excessive drowsiness (sedation), rash (unspecified), and vertigo. The exact incidence of these effects is unknown.
Orthostatic hypotension has been reported following intracavernosal injection of papaverine. Prolonged erection, or priapism is a serious complication of intracavernosal injection of papaverine. Beginning with a low initial trial dose can minimize the potential for this adverse effect and titrating to the lowest dose that produces a satisfactory response. Patients should be instructed to seek medical attention for erection lasting longer than 4 hours. Intracavernosal injection of papaverine may result in an injection site reaction. Local site reactions may include transient penile pain, ecchymosis, and penile fibrosis at the injection site. Fibrosis may be avoided by ensuring proper injection technique and limiting the frequency of injections.
One case of papaverine-induced seizures has been reported in the literature. Generalized convulsions developed following 300 mg of intra-arterial papaverine (internal carotid) in a patient being treated for symptomatic vasospasm after subarachnoid hemorrhage. This occurred despite therapeutic phenytoin levels. Repeat intra-arterial papaverine again produced seizures.
Severe, reversible thrombocytopenia related to intra-arterial papaverine has been described in one case report. On two separate occasions, the same patient developed severe thrombocytopenia following injection of papaverine into the right internal carotid artery. Laboratory data supported the diagnosis of immune-mediated papaverine-induced thrombocytopenia.
Increased intracranial pressure, hypertension, and sinus tachycardia have been noted during intra-arterial infusions of papaverine for vasospasm secondary to aneurysmal subarachnoid hemorrhage. These effects can be minimized by careful titration of papaverine in conjunction with hemodynamic monitoring.
QT prolongation, ventricular arrhythmias, and torsade de pointes are rare complications of intracoronary administration of papaverine. In one series, five of 391 patients (1.3%) experienced polymorphous ventricular tachycardia. Only one patient required electrical cardioversion for resolution of the arrhythmia.
Although the manufacturer indicates that papaverine should be administered with caution to patients with glaucoma, review of the literature suggests that cautious use is not warranted.
Papaverine is contraindicated in the presence of complete atrioventricular block (AV block). When conduction is depressed, the drug may produce transient ectopic rhythms of ventricular origin, either premature beats or paroxysmal tachycardia.
Patients with Parkinson's disease who are taking levodopa should avoid the use of papaverine. Loss of control of Parkinson's disease may result when papaverine is used in these patients. The mechanism of the interaction is unclear, but may be related to the blockage of dopamine receptors in the striatum by papaverine.
Papaverine may cause excessive drowsiness in some individuals. Instruct patients to use caution while driving or operating machinery.
Although papaverine may be used off-label for the treatment of erectile dysfunction, administration of papaverine via intracorporeal injection is contraindicated due to the risk of persistent priapism, which may require medical and surgical intervention. If not treated promptly, priapism can result in irreversible damage to the erectile tissue. Patients who have an erection lasting greater than 4 hours, whether painful or not, should seek emergency medical attention.
Intracoronary papaverine may cause torsade de pointes in a small number of patients. Caution should be exercised when administering intracoronary papaverine to patients with preexisting QT prolongation.
Papaverine is classified in FDA pregnancy risk category C. Following single subcutaneous doses of papaverine in rats, no teratogenic effects were reported. Safe use during pregnancy in humans has not been established. It is not known whether papaverine can affect reproduction capacity. According to the manufacturer, papaverine should only be given to a pregnant woman when clearly needed and when the potential benefits outweigh the potential hazards to the fetus. In addition, because papverine relaxes smooth muscle tone; use caution when considering administration to a woman in labor.
It is not known whether papaverine is excreted in human milk. According to the manufacturer, papaverine should be used with caution in women who are breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Clinical trials of extended-release papaverine capsules did not include enough geriatric patients to identify a difference in drug response as compared to younger patients. Subsequent clinical experience has not identified any differences. Nevertheless, due to an increased frequency of comorbidities and decreased hepatic and renal function, dosing in the elderly should start at the low end of the dosing range.
For the treatment of erectile dysfunction (ED)*:
Intracavernous dosage:
Adult males: Papaverine is used alone, or in combination with phentolamine, or with phentolamine plus alprostadil (prostaglandin E1 or PGE1). Individual dosages are determined by a series of trial injections under physician supervision. The injections should be given no more than 3 times per week, with a minimum of 24 hours between doses. The maximum amount of papaverine is 60 mg per dose when given in combination therapy. Triple drug therapy with papaverine, phentolamine, and alprostadil is most effective, with response rates of up to 92%. Studied dose ranges are as follows: monotherapy, 20 to 80 mg papaverine per injection; 2-drug regimen, 0.25 to 1.5 mg phentolamine plus 7.5 to 45 mg papaverine per injection; 3-drug regimen, 0.2 to 0.4 mg phentolamine plus 8 to 16 mg papaverine plus 10 to 20 mcg alprostadil per injection. Second-line treatment options for ED include intracavernous injections; such therapy is the most effective nonsurgical treatment for ED, with predictable and sustained response. However, it is invasive and carries notable side effects, including priapism and penile fibrosis. Careful dose selection, proper patient education, and continued monitoring by a prescribing physician is warranted for successful non-oral treatment of ED. Follow-up visits for ED patients, regardless of therapy, are necessary to determine whether therapy continues to be effective and whether cardiovascular health has significantly changed.
For the treatment of ischemic conditions associated with arterial vasospasm (arterial thromboembolism):
-for the treatment of cerebral and peripheral ischemia associated with arterial spasm:
Oral dosage (extended release capsules):
Adults: Initially, 150 mg PO every 12 hours. Dosage may be increased to 150 mg PO every 8 hours, or 300 mg PO every 12 hours.
-for the treatment of non-occlusive mesenteric ischemia:
Intra-arterial dosage:
Adults: 30 to 60 mg/hour as an intra-arterial infusion for 24 hours followed by angiographic evaluation. Infusion may be restarted for additional 24-hour periods followed by repeat angiograms until resolution of vasoconstriction and clinical signs and symptoms. Infusions have been maintained for as long as 5 days.
-for the evaluation of coronary flow reserve:
Intracoronary dosage:
Adults: 8 to 12 mg of 1 mg/mL dilution intracoronary, administered over 10 seconds.
-for the prevention of ischemic spinal cord injury following surgery involving aortic cross-clamping:
Intrathecal dosage (preservative-free injection only):
Adults: Inject 30 mg of 1% preservative-free papaverine solution intrathecally over 5 minutes.
For the treatment of arrhythmias due to myocardial ischemia (acute myocardial infarction* or angina*):
Intravenous or Intramuscular dosage:
Adults: 30 to 120 mg IV or IM every 3 hours as indicated. Papaverine IV must be injected slowly over 1 to 2 minutes.
-for the treatment of cardiac extrasystoles associated with myocardial ischemia:
Intravenous or Intramuscular dosage:
Adults: 30 mg IV or IM every 10 minutes, injected slowly over 1 to 2 minutes, for a total of 2 doses.
For intravascular catheter occlusion prophylaxis* (prolongation of peripheral arterial catheter patency*):
Intra-Arterial dosage:
Neonates, Infants, Children, and Adolescents: 30 mg of papaverine added to 250 mL of arterial catheter infusion solution (0.9% or 0.45% Sodium Chloride Injection with heparin 1 unit/mL) infused continuously at a rate of 1 mL/hour into a peripheral arterial catheter. Generally, avoid use in extremely premature neonates during the immediate period after birth when the risk of developing intracranial hemorrhage is highest.
Maximum Dosage Limits:
-Adults
600 mg/day PO for extended-release capsules.
-Geriatric
600 mg/day PO for extended-release capsules.
-Adolescents
Safety and efficacy have not been established. Maximum dosage information is not available.
-Children
Safety and efficacy have not been established. Maximum dosage information is not available.
-Infants
Safety and efficacy have not been established. Maximum dosage information is not available.
-Neonates
Safety and efficacy have not been established. Maximum dosage information is not available.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are necessary.
Intermittent hemodialysis
No dosage adjustment is needed.
*non-FDA-approved indication
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as diphenhydramine could lead to enhanced sedation.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as doxylamine could lead to enhanced sedation.
Acetaminophen; Diphenhydramine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as diphenhydramine could lead to enhanced sedation.
Alprazolam: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation.
Amobarbital: (Moderate) Concurrent use of papaverine with potent CNS depressants such as barbiturates could lead to enhanced sedation.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Papaverine is a benzylisoquinoline alkaloid of opium and may have synergistic effects with potent CNS depressants such as anxiolytics, sedatives, and hypnotics, which could lead to enhanced sedation.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as barbiturates could lead to enhanced sedation.
Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with papaverine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Barbiturates: (Moderate) Concurrent use of papaverine with potent CNS depressants such as barbiturates could lead to enhanced sedation.
Benzodiazepines: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation.
Buspirone: (Moderate) Concurrent use of papaverine with potent CNS depressants such as buspirone could lead to enhanced sedation.
Butalbital; Acetaminophen: (Moderate) Concurrent use of papaverine with potent CNS depressants such as barbiturates could lead to enhanced sedation.
Butalbital; Acetaminophen; Caffeine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as barbiturates could lead to enhanced sedation.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as barbiturates could lead to enhanced sedation.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as barbiturates could lead to enhanced sedation.
Carbidopa; Levodopa: (Major) The beneficial effects of levodopa in Parkinson's disease have been reported to be reversed by coadministration of papaverine; avoid concurrent use in these patients. Papaverine may block dopamine receptors in the striatum and result in loss of control of Parkinson's disease in patients who are taking levodopa.
Carbidopa; Levodopa; Entacapone: (Major) The beneficial effects of levodopa in Parkinson's disease have been reported to be reversed by coadministration of papaverine; avoid concurrent use in these patients. Papaverine may block dopamine receptors in the striatum and result in loss of control of Parkinson's disease in patients who are taking levodopa.
Chlordiazepoxide: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation.
Chlordiazepoxide; Amitriptyline: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation.
Chlordiazepoxide; Clidinium: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation.
Clonazepam: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation.
Clorazepate: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as diphenhydramine could lead to enhanced sedation.
Diazepam: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation.
Diphenhydramine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as diphenhydramine could lead to enhanced sedation.
Diphenhydramine; Ibuprofen: (Moderate) Concurrent use of papaverine with potent CNS depressants such as diphenhydramine could lead to enhanced sedation.
Diphenhydramine; Naproxen: (Moderate) Concurrent use of papaverine with potent CNS depressants such as diphenhydramine could lead to enhanced sedation.
Diphenhydramine; Phenylephrine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as diphenhydramine could lead to enhanced sedation.
Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with papaverine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
Doxylamine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as doxylamine could lead to enhanced sedation.
Doxylamine; Pyridoxine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as doxylamine could lead to enhanced sedation.
Droperidol: (Moderate) Concurrent use of papaverine with potent CNS depressants such as droperidol could lead to enhanced sedation.
Estazolam: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation.
Eszopiclone: (Moderate) Papaverine is a benzylisoquinoline alkaloid of opium and may have synergistic effects with potent CNS depressants such as anxiolytics, sedatives, and hypnotics, which could lead to enhanced sedation.
Etomidate: (Moderate) Papaverine is a benzylisoquinoline alkaloid of opium and may have synergistic effects with potent CNS depressants such as general anesthetics, which could lead to enhanced sedation.
Flurazepam: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation.
General anesthetics: (Moderate) Papaverine is a benzylisoquinoline alkaloid of opium and may have synergistic effects with potent CNS depressants such as general anesthetics, which could lead to enhanced sedation.
Hydroxyzine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as hydroxyzine could lead to enhanced sedation.
Isoflurane: (Moderate) Papaverine is a benzylisoquinoline alkaloid of opium and may have synergistic effects with potent CNS depressants such as general anesthetics, which could lead to enhanced sedation.
Ketamine: (Moderate) Papaverine is a benzylisoquinoline alkaloid of opium and may have synergistic effects with potent CNS depressants such as general anesthetics, which could lead to enhanced sedation.
Levodopa: (Major) The beneficial effects of levodopa in Parkinson's disease have been reported to be reversed by coadministration of papaverine; avoid concurrent use in these patients. Papaverine may block dopamine receptors in the striatum and result in loss of control of Parkinson's disease in patients who are taking levodopa.
Lorazepam: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation.
Meprobamate: (Moderate) Papaverine is a benzylisoquinoline alkaloid of opium and may have synergistic effects with potent CNS depressants such as anxiolytics, sedatives, and hypnotics, which could lead to enhanced sedation.
Methohexital: (Moderate) Concurrent use of papaverine with potent CNS depressants such as barbiturates could lead to enhanced sedation.
Midazolam: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation.
Oxazepam: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation.
Pentobarbital: (Moderate) Concurrent use of papaverine with potent CNS depressants such as barbiturates could lead to enhanced sedation.
Phenobarbital: (Moderate) Concurrent use of papaverine with potent CNS depressants such as barbiturates could lead to enhanced sedation.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Concurrent use of papaverine with potent CNS depressants such as barbiturates could lead to enhanced sedation.
Primidone: (Moderate) Concurrent use of papaverine with potent CNS depressants such as barbiturates could lead to enhanced sedation.
Propofol: (Moderate) Papaverine is a benzylisoquinoline alkaloid of opium and may have synergistic effects with potent CNS depressants such as general anesthetics, which could lead to enhanced sedation.
Quazepam: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation.
Remimazolam: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation.
Secobarbital: (Moderate) Concurrent use of papaverine with potent CNS depressants such as barbiturates could lead to enhanced sedation.
Sevoflurane: (Moderate) Papaverine is a benzylisoquinoline alkaloid of opium and may have synergistic effects with potent CNS depressants such as general anesthetics, which could lead to enhanced sedation.
Temazepam: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation.
Triazolam: (Moderate) Concurrent use of papaverine with potent CNS depressants such as benzodiazepines could lead to enhanced sedation.
Zaleplon: (Moderate) Papaverine is a benzylisoquinoline alkaloid of opium and may have synergistic effects with potent CNS depressants such as anxiolytics, sedatives, and hypnotics, which could lead to enhanced sedation.
Zolpidem: (Moderate) Papaverine is a benzylisoquinoline alkaloid of opium and may have synergistic effects with potent CNS depressants such as anxiolytics, sedatives, and hypnotics, which could lead to enhanced sedation.
Papaverine is a benzylisoquinoline alkaloid of opium. It is structurally different from morphine and codeine, which are phenanthrene alkaloids. Papaverine acts by inhibiting phosphodiesterase in smooth muscle cells, which produces increased tissue levels of cyclic adenosine monophosphate and cyclic guanosine 3,5-monophosphate and subsequent relaxation of vascular smooth muscle. Calcium ion channels in cell membranes may also be blocked by papaverine, resulting in a reduction of release of calcium from the intracellular spaces. Papaverine has a spasmolytic effect on smooth muscle of the large blood vessels, particularly those of the coronary, cerebral, peripheral and pulmonary arteries. This spasmolytic effect is unrelated to muscle innervation, and the muscle cell is still responsive to drugs and other stimuli which cause contraction. Relaxation of smooth muscle is also produced in the bronchial musculature, and in the gastrointestinal, biliary, and urinary tracts. Papaverine also relaxes cardiac muscle by directly depressing conduction and excitability of the myocardium and prolonging the refractory period.
Papaverine is administered orally and parenterally. Papaverine is metabolized in the liver to inactive metabolites, which are excreted in the urine.
-Route-Specific Pharmacokinetics
Oral Route
Following oral administration, papaverine is rapidly absorbed with peak plasma levels occurring within 1-2 hours. Oral bioavailability is approximately 54% and plasma protein binding is 90%.
-Special Populations
Hepatic Impairment
Data are lacking regarding the use of papaverine in hepatically impaired patients.