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Papaverine

Class: Vasodilating Agents, Miscellaneous
VA Class: CV900
CAS Number: 61-25-6
Brands: Para-Time SR

Medically reviewed by Drugs.com on Sep 21, 2021. Written by ASHP.

Introduction

Vasodilating agent; benzylisoquinoline alkaloid prepared synthetically or obtained from opium.

Uses for Papaverine

Cardiac and Vascular Uses

Relief of cerebral and peripheral ischemia associated with arterial spasm and myocardial ischemia complicated by arrhythmias.

Has been used IV and intra-arterially in treatment of acute vascular occlusion in conjunction with anticoagulants.

Treatment of angina pectoris; results not impressive at usual dosages. Not recommended as a substitute for nitroglycerin in anginal attacks.

Has been used in the treatment of other cardiovascular or vascular conditions including vascular encephalopathy associated with hypertensive disease, certain cerebral angiospastic states, and chronic peripheral vascular diseases (i.e., Raynaud’s syndrome, Buerger’s disease); however, use in these conditions has been superseded by more effective agents.

Erectile Dysfunction

Self-treatment of erectile dysfunction (ED, impotence).

Has been used alone or in combination with phentolamine and/or alprostadil in patients with neurogenic and/or limited vasculogenic impotence or those with psychogenic impotence, but efficacy in patients with a vasculogenic component of their impotence may be variable depending on the extent and type of vascular dysfunction.

The goal of therapy is to provide an erection of adequate rigidity and duration to be sexually functional while avoiding prolonged erection or priapism.

Some experts (American Urological Association [AUA]) recommend that selective phosphodiesterase (PDE) type 5 inhibitor therapy (sildenafil, tadalafil, vardenafil) be offered as first-line erectile dysfunction treatment unless contraindicated.

Intracavernosal therapy with papaverine and/or other drugs generally reserved for patients who do not respond to psychotherapy/behavioral therapy, vacuum constriction devices, and/or selective PDE type 5 inhibitors and in whom attempts at identifying and modifying any drug-related (e.g., certain antihypertensive agents) or other potential reversible medical cause of erectile dysfunction have proved inadequate.

Some clinicians currently prefer alprostadil, alone or combined with other agents, when intracavernosal treatment of impotence is indicated because of possible improved efficacy and decreased adverse effects (e.g., priapism, fibrotic changes) compared with papaverine therapy.

Choice of therapy for erectile dysfunction should be individualized taking into account differences in response, tolerability and safety, administration considerations, cost and patient reimbursement factors, experience and judgment of the clinician, and individual patient and partner preference, expectations, and satisfaction.

Do not use for enhancing erections in men who are not impotent.

Other Uses

Has been used in the treatment of GI spasms, dysmenorrhea, biliary or ureteral colic, bronchial asthma, cardiac arrhythmias, and other pathologic conditions; however, insufficient evidence to establish therapeutic value.

Papaverine Dosage and Administration

Administration

Administer orally, or by IM or slow IV injection.

Has been used intra-arterially in treatment of acute vascular occlusion in conjunction with anticoagulants.

Has been administered by intracavernous injection for the treatment of erectile dysfunction.

IV Administration

Slow IV injection preferred when an immediate effect is desired.

Rate of Administration

Inject slowly over a 1- to 2-minute period to minimize serious adverse effects (e.g., arrhythmias, fatal apnea). (See Cardiovascular and Respiratory Effects under Cautions.)

Dosage

Available as papaverine hydrochloride; dosage expressed in terms of salt.

Pediatric Patients

Cardiac and Vascular Use†
IV or IM

6 mg/kg daily (as 4 divided doses).

Adults

Cardiac and Vascular Use
Oral

Usually, 150 mg (extended-release capsules) every 8–12 hours.

Alternatively, 300 mg (extended-release capsules) every 12 hours.

75–300 mg (conventional tablets [no longer commercially available in US] 3–5 times daily, also has been used.

IV or IM

Usually, 30 mg; may repeat 30–120 mg every 3 hours as necessary.

Cardiac extrasystoles: May administer 2 doses 10 minutes apart.

Erectile Dysfunction†
Intracavernosal Self-injection†

2.5–37.5 mg. Usually, titrated up to 30 mg in combination with phentolamine mesylate 0.5–1 mg (range: 0.08–1.25 mg).

Tolerance with long-term use may require dosage increase.

Prescribing Limits

Adults

Cardiovascular Use
IV

960 mg daily.

Special Populations

No special population dosage recommendations at this time.

Cautions for Papaverine

Contraindications

  • Complete atrioventricular heart block.

  • Administer with extreme caution when cardiac conduction is depressed, because of increased risk of transient ectopic rhythms of ventricular origin (premature beats or paroxysmal tachycardia).

Warnings/Precautions

Warnings

Cardiovascular and Respiratory Effects

Administer IV slowly with caution; rapid injection may result in arrhythmias and fatal apnea.

Large parenteral doses can depress atrioventricular and intraventricular conduction; may result in serious arrhythmias.

Vasoactive Therapy

While some manufacturers have stated that papaverine hydrochloride injection is not indicated for the treatment of impotence via intracorporeal injection, the drug has been employed effectively via intracavernosal injection.

Do not use vasoactive therapy for impotence in patients who might have conditions predisposing to priapism (e.g., sickle cell anemia or trait, multiple myeloma, leukemia), in those with anatomic deformation of the penis (e.g., angulation, cavernosal fibrosis, Peyronie’s disease), or in men in whom sexual activity is inadvisable or contraindicated. Discontinue vasoactive therapy in patients who develop penile angulation, cavernosal fibrosis, or Peyronie’s disease during therapy.

Intracavernosal therapy (administered by self-injection) may be problematic in those receiving anticoagulants, who cannot tolerate transient hypotension, and those with poor manual dexterity, poor vision, or severe psychiatric disease.

Priapism Associated with Intracavernosal Injection

Consider possibility of persistent priapism (a medical emergency) associated with intracavernosal injection; may require immediate medical and/or surgical intervention. (See Advice to Patients.)

The risk of priapism can be reduced by careful patient instruction and dosage titration.

Management of priapism includes aspiration of cavernosal blood and/or intracavernous injection of an α-adrenergic agonist (e.g., metaraminol, phenylephrine) or dopamine. Rarely, more radical therapy for priapism (e.g., cavernospongiosus or Winter’s shunt) may be necessary, such as in patients with persistent priapism (e.g., longer than 24 hours).

Sensitivity Reactions

Hepatic Hypersensitivity

Hepatic hypersensitivity with GI symptoms, jaundice, eosinophilia, and altered hepatic function tests results reported.

If such hypersensitivity occurs, discontinue the drug.

General Precautions

Adequate Patient Monitoring

Administer papaverine injection only under the supervision of qualified clinician.

Glaucoma

Use with caution in patients with glaucoma.

Abuse and Dependence

Potential abuse and dependence to papaverine reported.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether papaverine distributes into human milk. Use with caution in nursing women.

Pediatric Use

Safety and efficacy of papaverine in pediatric patients not established.

However, children have received papaverine hydrochloride dosages of 6 mg/kg daily, divided into 4 IM or IV doses.

Common Adverse Effects

Following oral administration: Nausea, abdominal distress, anorexia, constipation, malaise, drowsiness, vertigo, sweating, headache, diarrhea, rash, flushing of the face, increased heart rate, increased depth of respirations, slight increase in BP, sedation.

Following IV administration: General discomfort, nausea, abdominal discomfort, anorexia, constipation, diarrhea, skin rash, malaise, headache, flushing, sweating, sedation, hepatitis, hypotension, hypertension, thrombosis at IV injection site.

Following intracavernosal administration: Priapism, transient pain, referred glans pain, burning, paresthesia.

Interactions for Papaverine

Specific Drugs

Drug

Interaction

Comments

CNS depressants

Possible increased papaverine effects

Levodopa

Papaverine may block dopamine receptors and interfere with the therapeutic effects of levodopa

Avoid concomitant use; do not use in patients with Parkinson's disease

Morphine

Possible synergism

Papaverine Pharmacokinetics

Absorption

Bioavailability

Readily absorbed from GI tract.

Onset

Fairly rapid.

Following intracavernosal injection, erectile response usually occurs within 10 minutes.

Duration

Oral administration of extended-release capsules may provide continuous drug release over a 12-hour period.

Following intracavernosal injection, erectile response may persist for 1 to several hours.

Plasma Concentrations

Constant plasma concentrations can be maintained with oral administration at 6-hour intervals.

Distribution

Extent

Distributed throughout the body, with highest concentrations in fat deposits and liver.

Not known if papaverine distributes into human milk.

Plasma Protein Binding

90%.

Elimination

Metabolism

Rapidly metabolized in the liver.

Elimination Route

Excreted in urine, principally as inactive metabolites.

Stability

Storage

Oral

Capsules

15–30°C. Protect from moisture.

Parenteral

Injection

15–30°C. Protect from light; keep in the original carton until time of use.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Incompatibility

Do not add papaverine hydrochloride injection to lactated Ringer’s injection because a precipitate would result.

Actions

  • Main therapeutic action is a direct spasmolytic effect on smooth muscles.

  • Spasmolytic effect most pronounced on blood vessels including the coronary, cerebral, pulmonary, and peripheral arteries; also relaxes smooth muscles of the bronchi, GI tract, ureters, and biliary system.

  • Relaxes cardiac muscle by directly depressing the excitability of the myocardium, prolonging the refractory period, and depressing conduction.

  • In the presence of vascular occlusion, may act by overcoming reflex vasoconstriction in collateral vessels.

  • Direct vasodilating action on cerebral blood vessels may explain benefit reported in cerebral vascular encephalopathy.

  • Minimal CNS actions; although large doses may have a depressant effect.

  • Weak calcium-channel activity with high doses.

  • Little, if any, analgesic action.

Advice to Patients

  • Advise patients receiving the drug via intracavernosal injection of potential for prolonged erections (priapism) and steps to take in the event that this serious adverse effect occurs.

  • Importance of seeking immediate medical attention if an erection persists >4 hours or is extremely painful.

  • Instruct patients receiving the drug via intracavernosal injection to visit their clinician regularly (e.g., at 3-month intervals) to assess therapeutic benefit, including the need for possible dosage adjustment, and of potential adverse effects associated with such therapy.

  • Importance of informing clinicians if risk factors for cardiovascular disease are present prior to initiating any treatment.

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Papaverine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Bulk

Powder

Oral

Capsules, extended-release

150 mg*

Papaverine Hydrochloride Capsules ER

Sandoz

Para-Time SR

Time-Cap

Parenteral

Injection

30 mg/mL*

Papaverine Hydrochloride Injection (with chlorobutanol 0.5% in multiple-dose vials or preservative-free in single-dose vials)

American Regent, Bedford

AHFS DI Essentials™. © Copyright 2022, Selected Revisions October 1, 2008. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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