Papaverine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection, as hydrochloride:

Generic: 30 mg/mL (2 mL, 10 mL [DSC])

Pharmacology

Mechanism of Action

Smooth muscle spasmolytic producing a generalized smooth muscle relaxation including: vasodilatation, gastrointestinal sphincter relaxation, bronchiolar muscle relaxation, and potentially a depressed myocardium (with large doses); muscle relaxation may occur due to inhibition or cyclic nucleotide phosphodiesterase, increasing cyclic AMP; muscle relaxation is unrelated to nerve innervation; papaverine increases cerebral blood flow in normal subjects; oxygen uptake is unaltered

Pharmacokinetics/Pharmacodynamics

Metabolism

Rapidly hepatic

Excretion

Primarily urine (as metabolites)

Onset of Action

Oral: Rapid

Half-Life Elimination

30 to 120 minutes

Protein Binding

~90%

Use: Labeled Indications

Various vascular spasms associated with smooth muscle spasms as in myocardial infarction, angina, peripheral and pulmonary embolism, peripheral vascular disease; cerebral angiospastic states; visceral spasms (ureteral, biliary, and GI colic). Note: Labeled uses have fallen out of favor; safer and more effective alternatives are available.

Use: Off Label

Cerebral vasospasm after mechanical thrombectomy in acute ischemic strokec

Data from a limited number of patients studied suggest that intra-arterial papaverine may be beneficial for the treatment of cerebral vasospasm resulting from mechanical thrombectomy in acute ischemic stroke Baltsavias 2015. Additional data may be necessary to further define the role of papaverine in this condition.

Vasospasm during harvesting mammary arteries for CABG surgeryb

Data from a randomized controlled trial in patients undergoing CABG surgery and harvesting of the left internal mammary artery (LIMA) supports the use of intraluminal papaverine to prevent or treat spasm after LIMA dissection when delivered to the pedicle Girard 2004. Additional trials may be necessary to further define the role of papaverine to treat spasm of the internal mammary artery.

Contraindications

Complete AV block

Dosage and Administration

Dosing: Adult

Note: Labeled uses have fallen out of favor; safer and more effective alternatives are available. The manufacturer's labeling recommends the following dosing:

Arterial spasm: IM, IV: 30 to 120 mg; may repeat dose every 3 hours; if cardiac extrasystole occurs during use, may administer 2 doses 10 minutes apart

Cerebral vasospasm after mechanical thrombectomy in acute ischemic stroke (off-label use): Intra-arterial: 30 mg/minute; amount infused depends on response of the spastic vessel; dosage administered in clinical study ranged from 45 to 120 mg (Baltsavias 2015). Additional data may be necessary to further define the role of papaverine in this condition.

Vasospasm during harvesting mammary arteries for CABG surgery (off-label use): Intra-arterial: 10 mg (1 mg/mL in NS) injected throughout the vessel after it has been harvested; avoid vascular wall infiltration (Girard 2004). Note: Administration techniques may vary.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Peripheral arterial catheter patency: Limited data available: Infants, Children, and Adolescents: Add 30 mg papaverine to an admixture of 250 mL NS or ¹/₂NS with heparin 1 unit/mL (Heulitt 1993; Kliegman 2007); infuse via peripheral arterial catheter; some centers report infusions at ≤1 mL/hour

Reconstitution

Solutions should be clear to pale yellow. Precipitates with lactated Ringer's.

Administration

IV: Administer by slow push (over 1 to 2 minutes). Rapid IV administration may result in arrhythmias and fatal apnea.

May be administered intra-arterially for cerebral vasospasm after mechanical thrombectomy in acute ischemic stroke (off-label use) or vasospasm during harvesting mammary arteries for CABG surgery (off-label use) once the artery has been dissected (Baltsavias 2015; Girard 2004).

Dietary Considerations

May be taken with food.

Storage

Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from light.

Drug Interactions

Levodopa-Containing Products: Papaverine may enhance the hypotensive effect of Levodopa-Containing Products. Papaverine may diminish the therapeutic effect of Levodopa-Containing Products. Monitor therapy

Adverse Reactions

Frequency not defined.

Cardiovascular: Cardiac arrhythmia (with rapid IV use), flushing, hypertension (mild), tachycardia

Central nervous system: Headache, malaise, sedation, vertigo

Dermatologic: Diaphoresis, skin rash

Gastrointestinal: Abdominal distress, anorexia, constipation, diarrhea, nausea

Hepatic: Hepatic cirrhosis

Hypersensitivity: Hypersensitivity reaction (hepatic)

Respiratory: Apnea (with rapid IV use)

<1%, postmarketing, and/or case reports: Hepatitis

Warnings/Precautions

Concerns related to adverse effects:

• Arrhythmias: May (in large doses or with rapid infusion) depress AV and intraventricular cardiac conduction leading to serious arrhythmias (eg, premature beats, paroxysmal tachycardia).
• Hepatitis: May cause hepatic hypersensitivity; discontinue use if GI symptoms, jaundice, eosinophilia, or abnormal LFTs occur.

Disease-related concerns:

• Glaucoma: Use with caution in patients with glaucoma.

Other warnings/precautions:

• Appropriate use: Not indicated for treatment of impotence by intracorporeal injection; persistent priapism may occur.

Monitoring Parameters

Blood pressure, heart rate

Pregnancy

Pregnancy Risk Factor

C

Pregnancy Considerations

Teratogenic effects have not been observed in animal reproduction studies.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience nausea, abdominal pain, fatigue, constipation, diarrhea, lack of appetite, loss of strength and energy, flushing, or sweating a lot. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin), fast heartbeat, severe headache, dizziness, passing out, vision changes, or abnormal heartbeat (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.