Generic Name: Papaverine Hydrochloride
Class: Vasodilating Agents, Miscellaneous
VA Class: CV900
CAS Number: 61-25-6
Uses for Para-Time SR
Cardiac and Vascular Uses
Has been used IV and intra-arterially in treatment of acute vascular occlusion in conjunction with anticoagulants.a
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peripheral vascular diseases (i.e., Raynaud’s syndrome, Buerger’s disease); however, use in these conditions has been superseded by more effective agents.a
Has been used alone or in combination with phentolamine and/or alprostadil in patients with neurogenic103 105 106 108 110 112 113 115 116 118 119 120 128 129 132 and/or limited vasculogenic impotence 103 105 106 108 110 112 113 115 116 120 121 128 129 132 or those with psychogenic impotence,105 106 108 120 128 129 132 but efficacy in patients with a vasculogenic component of their impotence may be variable depending on the extent and type of vascular dysfunction.103 108 110 115 120 128 129
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.178
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.110 130
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.130 149 150 151 152 153 154
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.170 171 172 173 174 175 176 177 178
Do not use for enhancing erections in men who are not impotent.154
Has been used in the treatment of GI spasms, dysmenorrhea, biliary or ureteral colic, bronchial asthma, cardiac arrhythmias, and other pathologic conditions†;181 a however, insufficient evidence to establish therapeutic value.a
Para-Time SR Dosage and Administration
Has been used intra-arterially in treatment of acute vascular occlusion in conjunction with anticoagulants.a
Rate of Administration
Cardiac and Vascular Use†
IV or IM
6 mg/kg daily (as 4 divided doses).a
Cardiac and Vascular Use
Alternatively, 300 mg (extended-release capsules) every 12 hours.a
75–300 mg (conventional tablets [no longer commercially available in US] 3–5 times daily, also has been used.a
IV or IM
960 mg daily.
Cautions for Para-Time SR
Cardiovascular and Respiratory Effects
Administer IV slowly with caution; rapid injection may result in arrhythmias and fatal apnea.a
Large parenteral doses can depress atrioventricular and intraventricular conduction; may result in serious arrhythmias.180
While some manufacturers have stated that papaverine hydrochloride injection is not indicated for the treatment of impotence via intracorporeal injection,133 134 135 181 the drug has been employed effectively via intracavernosal injection.103 105 106 107 108 110 112 113 114 115 116 118 119 120 121 126 128 130 132 137 142
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.110 143 152 154 164 165 167 Discontinue vasoactive therapy in patients who develop penile angulation, cavernosal fibrosis, or Peyronie’s disease during therapy.143 167
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.130
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.103 105 106 107 108 110 113 115 116 120 122 125 127 129 130 131 132 137 178 181 a (See Advice to Patients.)
Management of priapism includes aspiration of cavernosal blood105 110 113 115 116 120 127 129 and/or intracavernous injection of an α-adrenergic agonist (e.g., metaraminol, phenylephrine) or dopamine.103 105 106 107 108 109 110 111 113 115 120 127 129 137 179 Rarely, more radical therapy for priapism (e.g., cavernospongiosus or Winter’s shunt) may be necessary,104 105 106 110 129 179 such as in patients with persistent priapism (e.g., longer than 24 hours).104 110
Adequate Patient Monitoring
Abuse and Dependence
However, children have received papaverine hydrochloride dosages of 6 mg/kg daily, divided into 4 IM or IV doses.a
Common Adverse Effects
Following oral administration: Nausea,a abdominal distress,180 a anorexia,180 a constipation,180 a malaise,180 a drowsiness,a vertigo,180 a sweating,180 a headache,180 a diarrhea,180 a rash,180 a flushing of the face,180 a increased heart rate,180 a increased depth of respirations,180 a slight increase in BP,180 a sedation.181 a
Following IV administration: General discomfort,181 nausea,181 abdominal discomfort,181 anorexia,181 constipation,181 diarrhea,181 skin rash,181 malaise,181 headache,181 flushing,181 sweating,181 sedation,181 hepatitis,181 hypotension,181 hypertension,181 thrombosis at IV injection site.a
Following intracavernosal administration: Priapism,103 105 106 107 108 110 113 115 116 120 122 125 127 129 130 131 132 137 178 transient pain,105 108 110 129 referred glans pain,108 110 129 burning,103 paresthesia.105 110 129
Interactions for Para-Time SR
Possible increased papaverine effects a
Papaverine may block dopamine receptors and interfere with the therapeutic effects of levodopa a
Avoid concomitant use; do not use in patients with Parkinson's diseasea
Para-Time SR Pharmacokinetics
Readily absorbed from GI tract.a
Oral administration of extended-release capsules may provide continuous drug release over a 12-hour period.a
Distributed throughout the body, with highest concentrations in fat deposits and liver.181
Plasma Protein Binding
For information on systemic interactions resulting from concomitant use, see Interactions.
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.180 181 a
In the presence of vascular occlusion, may act by overcoming reflex vasoconstriction in collateral vessels.a
Direct vasodilating action on cerebral blood vessels may explain benefit reported in cerebral vascular encephalopathy.180
Little, if any, analgesic action.a
Advice to Patients
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.143 147 159 167
Importance of informing clinicians if risk factors for cardiovascular disease are present prior to initiating any treatment.a
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Papaverine Hydrochloride Capsules ER
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, 2004-2016, Selected Revisions October 1, 2008. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.
100. Tu YH, Allen LV Jr, Wang DP. Stability of papaverine hydrochloride and phentolamine mesylate in injectable mixtures. Am J Hosp Pharm. 1987; 44:2524-7. [PubMed 2446497]
101. Romankiewicz JA, McManus J, Gotz VP et al. Medications not to be refrigerated. Am J Hosp Pharm. 1979; 36:1541-5. [PubMed 517543]
102. Stillwell S (Eli Lilly and Company, Indianapolis, IN): Personal communication; 1986 Sept 10.
103. Sidi AA, Cameron JS, Duffy LM et al. Intracavernous drug-induced erections in the management of male erectile dysfunction: experience with 100 patients. J Urol. 1986; 135:704-6. [IDIS 214073] [PubMed 2421014]
104. Lindoro J, Castro JC, Cruz F et al. Treatment of priapism. Lancet. 1984; 2:1348. [PubMed 6150362]
105. Anon. Intracavernous injections for impotence. Med Lett Drugs Ther. 1987; 29:95-6. [PubMed 3670212]
106. Robinette MA, Moffat MJ. Intracorporal injection of papaverine and phentolamine in the management of impotence. Br J Urol. 1986; 58:692-5. [PubMed 3801830]
107. Ellis LR, Nellans RE, Kramer-Levien DJ et al. Evaluation of the first 300 patients treated at an outpatient center for male sexual dysfunction. West J Med. 1987; 147:296-300. [IDIS 233499] [PubMed 3673062]
108. Nellans RE, Ellis LR, Kramer-Levien D. Pharmacological erection: diagnosis and treatment applications in 69 patients. J Urol. 1987; 138:52-4. [IDIS 232011] [PubMed 2439712]
109. Fernandez JA, Basha MA, Wilson GC. Emergency treatment of papaverine priapism. J Emerg Med. 1987; 5:289-91. [PubMed 3624835]
110. Lue TF, Tanagho EA. Physiology of erection and pharmacological management of impotence. J Urol. 1987; 137:829-36. [IDIS 229174] [PubMed 3553617]
111. Mizutani M, Nakano H, Sagami K et al. Treatment of post-traumatic priapism by intracavernous injection of α-stimulant. Urol Int. 1986; 41:312-4. [PubMed 3787856]
112. Sidi Ami, Cameron JS, Dykstra DD et al. Vasoactive intracavernous pharmacotherapy for the treatment of erectile impotence in men with spinal cord injury. J Urol. 1987; 138:539-42. [IDIS 234478] [PubMed 2442418]
113. Gasser TC, Roach RM, Larsen EH et al. Intracavernous self-injection with phentolamine and papaverine for the treatment of impotence. J Urol. 1987; 137:678-80. [IDIS 227800] [PubMed 3550149]
114. Larsen EH, Gasser TC, Bruskewitz RC. Fibrosis of corpus cavernosum after intracavernous injection of phentolamine/papaverine. J Urol. 1987; 137:292-3. [IDIS 225679] [PubMed 3806824]
115. Trapp JD. Pharmacologic erection program for the treatment of male impotence. South Med J. 1987; 60:426-7.
116. Zorgniotti AW, Lefleur RS. Auto-injection of the corpus cavernosum with a vasoactive drug combination for vasculogenic impotence. J Urol. 1985; 133:39-41. [PubMed 2578067]
117. Juenemann KP, Lue TF, Fournier GR Jr et al. Hemodynamics of papaverine- and phentolamine-induced penile erection. J Urol. 1986; 136:158-61. [PubMed 3712604]
118. Wyndaele JJ, de Meyer JM, de Sy WA et al. Intracavernous injection of vasoactive drugs, an alternative for treating impotence in spinal cord injury patients. Paraplegia. 1986; 24:271-5. [PubMed 3774363]
119. Al-Juburi AZ, O’Donnell PD. Penile self-injection for impotence in patients after radical cystectomy-ileal loop. Urology. 1987; 30:29-30. [PubMed 3603906]
120. Kiely EA, Williams G, Goldie L. Assessment of the immediate and long-term effects of pharmacologically induced penile erections in the treatment of psychogenic and organic impotence. Br J Urol. 1987; 59:164-9. [PubMed 3828713]
121. Puyau FA, Lewis RW, Balkin P et al. Dynamic corpus cavernosography: effect of papaverine injection. Radiology. 1987; 164:179-82. [IDIS 232219] [PubMed 3588901]
122. Brindley GS. Maintenance treatment of erectile impotence by cavernosal unstriated muscle relaxant injection. Br J Psychiatry. 1986; 149:210-5. [PubMed 3640652]
123. Turini D, Barbanti G, Beneforti P et al. Intracavernous therapy in impotence after pelvic trauma: a preliminary study. Eur Urol. 1986; 12:413-7. [PubMed 3816897]
124. Virag R, Frydman D, Legman M et al. Intracavernous injection of papaverine as a diagnostic and therapeutic method in erectile failure. Angiology. 1984; 35:79-87. [PubMed 6696289]
125. Halsted DS, Weigel JW, Noble MJ et al. Papaverine-induced priapism: 2 case reports. J Urol. 1986; 136:109-10. [IDIS 217940] [PubMed 3712593]
126. Zorgniotti AW. Corpus cavernosum blockade for impotence: practical aspects and results in 250 cases. J Urol. 1986; 135:306A.
127. van Driel MF, de Vries AI, Mensink HJA. Intracavernous self-injection of papaverine in the treatment of erectile impotence after major surgery. J Enterostom Ther. 1987; 14:101-4.
128. Williams G. Impotence: treatment by autoinjection of vasoactive drugs. BMJ. 1987; 295:1279. [IDIS 235999] [PubMed 3120975]
129. Anon. Intracavernous injections for impotence. Med Lett Drugs Ther. 1990; 32:116-7. [PubMed 2255296]
130. NIH Consensus Development Panel on Impotence. JAMA. 1993; 270:83-90.
131. Anon. Vasodilators provide new therapy for erectile dysfunction. F-D-C Rep. 1992; 54:16-7.
132. Krane RJ, Goldstein I, Saenz de Tejada I. Impotence. N Engl J Med. 1989; 321:1648-59. [PubMed 2685600]
133. Eli Lilly and Company. Papaverine hydrochloride injection prescribing information. Indianapolis, IN; 1994 Oct.
134. Lilly Research Laboratories, Indianapolis, IN: Personal commumnication; 1994 Dec.
135. Eli Lilly and Company, Indianapolis, IN: Personal communication; 1994 Dec.
136. Eli Lilly and Company, Indianapolis, IN: Personal communication; 1994 Aug.
137. Kirby RS. Impotence: diagnosis and management of male erectile dysfunction. BMJ. 1994; 308:957-61. [IDIS 328981] [PubMed 8173405]
138. Bennett AH, Carpenter AJ, Barada JH. An Improved vasoactive drug combination for a pharmacological erection program. J Urol. 1991; 146:1564-5. [IDIS 296354] [PubMed 1719248]
139. Montorsi F, Guazzoni G, Bergamaschi F et al. Four-drug intracavernous therapy for impotence due to corporeal veno-occlusive dysfunction. J Urol. 1993; 149:1291-5. [IDIS 313863] [PubMed 7683061]
140. Montorsi F, Guazzoni G, Bergamaschi F et al. Effectiveness and safety of multidrug intracavernous therapy for vasculogenic impotence. Urology. 1993; 42:554-8. [PubMed 7694416]
141. von Heyden B, Donatuucci CF, Kaula N et al. Intracavernous pharmacotherapy for impotence: selection of appropriate agent and dose. J Urol. 1993; 149:1288-90. [IDIS 313862] [PubMed 8479018]
142. Reviewers’ comments (personal observations).
143. The Upjohn Company. Caverject (alprostadil) injection for intracavernosal use prescribing information. Kalamazoo, MI; 1995 Jul.
144. Linet OI, Ogrinc FG. Dose-escalating study with maintenance phase using alprostadil (prostaglandin E1, PGE1) sterile powder in patients with erectile dysfunction. Technical Report No. 9124-93-006. The Upjohn Company: Kalamazoo, MI; 1993 Dec 3.
145. Linet OI, Ogrinc FG. Long-term safety study with alprostadil sterile powder (alprostadil S.Po.; prostaglandin E1, PGE1) in patients with erectile dysfunction. Technical Report No. 9124-93-007. The Upjohn Company: Kalamazoo, MI; 1993 Dec 10.
146. Linet OI, Ogrinc FG. Dose- escalating study with maintenance phase using alprostadil (prostaglandin E1, PGE1) sterile powder (S.Po.) in elderly patients with erectile dysfunction. Technical Report No. 9124- 95-002. The Upjohn Company: Kalamazoo, MI; 1995 Jan 17.
147. Linet OI. Clinical pharmacology of alprostadil. In: Goldstein I, Lue TF, eds. The role of alprostadil in the diagnosis and treatment of erectile dysfunction. Princeton: Excerpta Medica; 1993:28-39.
148. Ishii N, Watanabe H, Irisawa C et al. Intracavernous injection of prostaglandin E1 for the treatment of erectile impotence. J Urol. 1989; 141:323-5. [IDIS 251538] [PubMed 2913354]
149. Allen RP, Engel RM, Smolev JK et al. Objective double-blind evaluation of erectile function with intracorporeal papaverine in combination with phentolamine and/or prostaglandin E1. J Urol. 1992; 148:1181-3. [IDIS 303448] [PubMed 1404632]
150. Godschalk MF, Chen J, Katz PG et al. Treatment of erectile failure with prostaglandin E1: a double-blind, placebo-controlled, dose-response study. J Urol. 1994; 151:1530-2. [IDIS 329635] [PubMed 8189563]
151. Chen J, Godschalk M, Katz PG et al. The lowest effective dose of prostaglandin E1 as treatment for erectile dysfunction. J Urol. 1995; 153:80-1. [IDIS 340107] [PubMed 7966797]
152. Godschalk MF, Chen J, Katz PG et al. Prostaglandin E1 as treatment for erectile failure in elderly men. J Am Geriatr Soc. 1994; 42:1263-5. [IDIS 339613] [PubMed 7983289]
153. Porst H. Prostaglandin E1 and the nitric oxide donor linsidomine for erectile failure: a diagnostic comparative study of 40 patients. J Urol. 1993; 149:1280-3. [IDIS 313861] [PubMed 8479015]
154. The Upjohn Company, Kalamazoo, MI: Personal communication.
155. Porst H. Prostaglandin E1 in male impotence—its diagnostic and therapeutic use in 2000 patients. Int J Impotence Res. 1992; 4(Suppl 2):A88.
156. Whitehead ED. Impotence: should primary care physicians give penile injections? Geriatrics. 1995; 50:14. Letter. (IDIS 341817)
157. Gerber GS, Levine LA. Pharmacological erection program using prostaglandin E1. J Urol. 1991; 146:786-9. [IDIS 287641] [PubMed 1875494]
158. Artoux MJ, McQueen KD. Alprostadil in impotence. DICE. 1991; 25:363-6.
159. Linet OI, Neff LL. Intracavernous prostaglandin E1 in erectile dysfunction. Clin Investig. 1994; 72:139-49. [PubMed 8186662]
160. Ravnik-Oblak M, Oblak C, Vodusek DB et al. Intracavernous injection of prostaglandin E1 in impotent diabetic men. Int J Impotence Res. 1990; 2:143-49.
161. Hirsch IH, Bagley DH, Christinzio J. Dosage considerations in the self-administration of PGE-1 for erectile dysfunction. J Urol. 1990; 143(Suppl):305A.
162. Montorsi F, Guazzoni G, Bergamaschi F et al. Clinical reliability of multi-drug intracavernous vasoactive pharmacotherapy for diabetic impotence. Acta Diabetol. 1994; 31:1-5. [PubMed 8043890]
163. Whitehead ED, Klyde BJ, Zussman S et al. Treatment alternatives for impotence. Postgrad Med. 1990; 88:139-52. [IDIS 269901] [PubMed 2199954]
164. Hwang TIS, Yang CR, Wang SJ et al. Impotence evaluated by the use of prostaglandin E1. J Urol. 1989; 141:1357-9. [IDIS 255242] [PubMed 2724434]
165. von Heyden B, Donatucci CF, Marshall GA et al. A prostaglandin E1 dose-response study in man. J Urol. 1993; 150:1825-8. [IDIS 321902] [PubMed 8230515]
166. Murray FT, Geisser M, Murphy TC. Evaluation and treatment of erectile dysfunction. Am J Med Sci. 1995; 309:99-109. [IDIS 342934] [PubMed 7847449]
167. Bénard F, Lue TF. Self-administration in the pharmacological treatment of impotence. Drugs. 1990; 39:394-8. [PubMed 2184008]
168. Duffy LM, Sidi AA, Lange PH. Vasoactive intracavernous pharmacotherapy—the nursing role in teaching self-injection therapy. J Urol. 1987; 138:1198-200. [IDIS 247278] [PubMed 3669166]
169. Montague DK. Editorial: treatment of erectile dysfunction. J Urol. 1993; 150:1833. [IDIS 321904] [PubMed 8230516]
170. Goldstein I, Lue TF, Padma-Nathan H et al. Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med. 1998; 338:1397-404. [IDIS 405966] [PubMed 9580646]
171. Goldstein I, Rosen RC, Steers WD. Sildenafil in the treatment of erectile dysfunction. N Engl J Med. 1998; 339:701-2.
172. Standing Medical Advisory Committee, United Kingdom Department of Health. The use of sildenafil in the treatment of erectile dysfunction. London; November 9,1998. From the United Kingdom Department of Health Web Site ().
173. Lipshultz LI, Kim ED. Treatment of erectile dysfunction in men with diabetes. JAMA. 1999; 281:465-6. [IDIS 418627] [PubMed 9952210]
174. Pfizer Inc, New York, NY: Personal communication on sildenafil.
175. Reviewers’ comments (personal observations) on sildenafil.
176. The Process of Care Consensus Panel. Position paper: the process of care model for evaluation and treatment of erectile dysfunction. Int J Impotence Res. 1999; 11:59-70.
177. Sarramon JP. Editorial comments on the process of care model for evaluation and treatment of erectile dysfunction. Int J Impotence Res. 1999; 11:73.
178. Erectile Dysfunction Guideline Update Panel, American Urological Association Education and Research. Management of erectile dysfunction: An update. 2005. Available at (. Accessed 2005 Oct. 20.
179. Erectile Dysfunction Guideline Update Panel, American Urological Association Education and Research. Priapism: Guideline on the management of priapism. 2003. Available at (. Accessed 2005 Oct. 20.
180. Eon Labs. Papaverine hydrochloride sustained release capsules prescribing information. Laurelton, NY; 2005 Mar.
181. American Regent, Inc. Papaverine hydrochloride injection prescribing information. Shirley, NY; 2003 Jan.
182. Sandoz Corporation. Princeton, NJ: Personal communication.
183. United Research. Philadelphia, PA: Personal communication.
184. American Regent. Shirley, NY: Personal communication.
a. AHFS drug information 2007. McEvoy GK, ed. Papaverine. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1796–8.