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papaverine hydrochloride
Classes
Other Cardiovascular Agents
Administration
Papaverine may be administered without regard to meals.
Papaverine capsules should be swallowed whole; do not chew, open, break, or crush.
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.
No dilution necessary.
Inject papaverine IV into a peripheral vein over 1 to 2 minutes. Blood pressure should be monitored frequently.
No dilution necessary.
Inject papaverine deeply into a large muscle. Aspirate prior to injection to avoid injection into a blood vessel.
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.
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 After injection, the syringe should be withdrawn.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.
Adverse Reactions
cirrhosis / Delayed / 0-1.0
seizures / Delayed / 0-1.0
ventricular tachycardia / Early / 0-1.0
torsade de pointes / Rapid / 0-1.0
increased intracranial pressure / Early / Incidence not known
hepatitis / Delayed / 0-1.0
thrombocytopenia / Delayed / 0-1.0
QT prolongation / Rapid / 0-1.0
constipation / Delayed / Incidence not known
hypertension / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known
orthostatic hypotension / Delayed / Incidence not known
penile pain / Rapid / Incidence not known
penile fibrosis / Delayed / Incidence not known
priapism / Early / Incidence not known
abdominal pain / Early / Incidence not known
vertigo / Early / Incidence not known
diarrhea / Early / Incidence not known
nausea / Early / Incidence not known
rash / Early / Incidence not known
headache / Early / Incidence not known
flushing / Rapid / Incidence not known
malaise / Early / Incidence not known
drowsiness / Early / Incidence not known
anorexia / Delayed / Incidence not known
diaphoresis / Early / Incidence not known
injection site reaction / Rapid / Incidence not known
Dea Class
Rx
Description
Smooth muscle relaxant marketed for relief of cerebral and peripheral ischemia secondary to arterial spasm
FDA Advisory Committee (1979) concluded insufficient data to support marketed indications and recommended market withdrawal; papaverine remains available despite the FDA Advisory recommendation
Off-label uses include cardiac procedures or to treat erectile dysfunction (ED)
Dosage And Indications
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.
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.
8 to 12 mg of 1 mg/mL dilution intracoronary, administered over 10 seconds.
Inject 30 mg of 1% preservative-free papaverine solution intrathecally over 5 minutes.
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.
30 mg IV or IM every 10 minutes, injected slowly over 1 to 2 minutes, for a total of 2 doses.
30 to 120 mg IV or IM every 3 hours as indicated. Papaverine IV must be injected slowly over 1 to 2 minutes.
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.
†Indicates off-label use
Dosing Considerations
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
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.
Drug Interactions
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.
Butabarbital: (Moderate) Concurrent use of papaverine with potent CNS depressants such as barbiturates 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.
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.
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.
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.
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.
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.
How Supplied
Papaverine Hydrochloride Intramuscular Inj Sol: 1mL, 30mg
Papaverine Hydrochloride Intravenous Inj Sol: 1mL, 30mg
Maximum Dosage
600 mg/day PO for extended-release capsules.
600 mg/day PO for extended-release capsules.
Safety and efficacy have not been established. Maximum dosage information is not available.
Safety and efficacy have not been established. Maximum dosage information is not available.
Safety and efficacy have not been established. Maximum dosage information is not available.
Safety and efficacy have not been established. Maximum dosage information is not available.
Mechanism Of Action
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.
Pharmacokinetics
Papaverine is administered orally and parenterally. Papaverine is metabolized in the liver to inactive metabolites, which are excreted in the urine.
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%.
Pregnancy And Lactation
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.