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{{drugbox
{{DrugProjectFormSinglePage
| IUPAC_name = 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxy-isoquinoline
|authorTag={{AV}}
| image = Papaverin - Papaverine.svg
|genericName=Papaverine
| CAS_number = 61-25-6
|aOrAn=a
| ATC_prefix = A03
|drugClass=[[phosphodiesterase]] [[inhibitor]]
| ATC_suffix = AD01
|indicationType=treatment
| ATC_supplemental = {{ATC|G04|BE02}}
|indication=vascular spasm associated with acute [[myocardial infarction]] ([[coronary occlusion]]), [[angina pectoris]], [[peripheral vascular disease]], peripheral and [[pulmonary embolism]]
| PubChem = 4680
|adverseReactions=general discomfort, [[nausea]], [[abdominal discomfort]], [[anorexia]], [[skin rash]], [[malaise]], [[vertigo]] and [[headache]].
| DrugBank = APRD00628
|blackBoxWarningTitle=Title
| C=20 | H=21 | N=1 | O=4
|blackBoxWarningBody=<i><span style="color:#FF0000;">ConditionName: </span></i>
| molecular_weight = 339.385 g/mol{{ref_label|1|1|c}}
 
| bioavailability = 80%{{ref_label|3|3|a}}
* Content
| protein_bound = ~90%
 
| metabolism = [[Hepatic]]{{ref_label|3|3|b}}
<!--Adult Indications and Dosage-->
| elimination_half-life = 1.5–2 hours{{ref_label|3|3|c}}
 
| pregnancy_category = [[United States|USA]]: C{{ref_label|4|4|a}}
<!--FDA-Labeled Indications and Dosage (Adult)-->
| legal_status =
|fdaLIADAdult=*Papaverine is recommended in various conditions accompanied by spasm of smooth muscle, such as vascular spasm associated with acute [[myocardial infarction]] ([[coronary occlusion]]), [[angina pectoris]], peripheral and [[pulmonary embolism]], [[peripheral vascular disease]] in which there is a vasospastic element, or certain cerebral angiospastic states; and visceral spasm, as in ureteral, biliary, or gastrointestinal [[colic]].
| routes_of_administration = Oral, [[intravenous]], [[intramuscular]], rectal,{{ref_label|5|5|a}} [[intracavernosal]]
* Dosage
| excretion = [[Renal]]{{ref_label|3|3|d}}
:*Papaverine Hydrochloride may be administered intravenously or intramuscularly. The intravenous route is recommended when an immediate effect is desired, but the drug must be injected slowly over the course of 1 or 2 minutes to avoid uncomfortable or alarming side effects.
}}
 
{{SI}}
:*Parenteral administration of papaverine hydrochloride in doses of 1 to 4 mL is repeated every 3 hours as indicated. In the treatment of [[cardiac extrasystoles]], 2 doses may be given 10 minutes apart.
{{EH}}
 
 
 
<!--Off-Label Use and Dosage (Adult)-->
 
<!--Guideline-Supported Use (Adult)-->
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Papaverine in adult patients.
 
<!--Non–Guideline-Supported Use (Adult)-->
|offLabelAdultNoGuideSupport=<!--Pediatric Indications and Dosage-->
 
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed=Safety and effectiveness in children have not been established.
<!--Off-Label Use and Dosage (Pediatric)-->
 
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Papaverine in pediatric patients.
 
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Papaverine in pediatric patients.
|contraindications======Complete atrioventricular heart block=====
*Intravenous injection of papaverine is contraindicated in the presence of [[complete atrioventricular heart block]]. When conduction is depressed, the drug may produce transient [[ectopic rhythms]] of ventricular origin, either [[premature beats]] or [[paroxysmal tachycardia]].
=====Impotence=====
*Papaverine Hydrochloride is not indicated for the treatment of [[impotence]] by [[intracorporeal injection]]. The [[intracorporeal injection]] of papaverine hydrochloride has been reported to have resulted in persistent [[priapism]] requiring medical and surgical intervention.
 
<!--Warnings-->
|warnings=====Precautions====
 
*Papaverine Hydrochloride Injection, USP, should not be added to Lactated Ringer’s Injection, because precipitation would result.
 
*Papaverine Hydrochloride should be used with caution in patients with glaucoma. The medication should be discontinued if hepatic [[hypersensitivity]] with gastrointestinal symptoms, [[jaundice]], or [[eosinophilia]] becomes evident or if [[liver function test]] values become altered.
*[[Drug dependence]] resulting from the abuse of many of the selective depressants, including papaverine hydrochloride, has been reported.
<!--Adverse Reactions-->
 
<!--Clinical Trials Experience-->
|clinicalTrials=*The following side effects have been reported: general discomfort, [[nausea]], [[abdominal discomfort]], [[anorexia]], [[constipation]] or [[diarrhea]], [[skin rash]], [[malaise]], [[vertigo]], [[headache]], intensive [[flushing]] of the face, [[perspiration]], increase in the depth of respiration, increase in [[heart rate]], a slight rise in [[blood pressure]], and excessive [[sedation]].
 
*[[Hepatitis]], probably related to an immune mechanism, has been reported infrequently. Rarely, this has progressed to [[cirrhosis]].
<!--Postmarketing Experience-->
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of Papaverine in the drug label.
 
 
<!--Drug Interactions-->
|FDAPregCat=C
|useInPregnancyFDA=*No teratogenic effects were observed in rats when papaverine hydrochloride was administered subcutaneously as a single agent. It is not known whether papaverine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. *Papaverine Hydrochloride should be given to a pregnant woman only if clearly needed.
|useInPregnancyAUS=There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Papaverine in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of Papaverine during labor and delivery.
|useInNursing=*It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when papaverine hydrochloride is administered to a nursing woman.
|useInPed=Safety and effectiveness in children have not been established.
|useInGeri=There is no FDA guidance on the use of Papaverine with respect to geriatric patients.
|useInGender=There is no FDA guidance on the use of Papaverine with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of Papaverine with respect to specific racial populations.
|useInRenalImpair=There is no FDA guidance on the use of Papaverine in patients with [[renal impairment]].
|useInHepaticImpair=There is no FDA guidance on the use of Papaverine in patients with hepatic impairment.
|useInReproPotential=There is no FDA guidance on the use of Papaverine in women of reproductive potentials and males.
|useInImmunocomp=There is no FDA guidance one the use of Papaverine in patients who are [[immunocompromised]].
 
<!--Administration and Monitoring-->
|administration=* Intravenously or Intramuscularly
|monitoring=There is limited information regarding <i>Monitoring</i> of Papaverine in the drug label.
 
 
<!--IV Compatibility-->
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of Papaverine in the drug label.
 
<!--Overdosage-->
|overdose======Signs and Symptoms=====
*The symptoms of toxicity from papaverine hydrochloride often result from vasomotor instability and include [[nausea]], [[vomiting]], [[weakness]], central nervous system depression, [[nystagmus]], [[diplopia]], [[diaphoresis]], [[flushing]], [[dizziness]], and [[sinus tachycardia]].
* In large overdoses, papaverine is a potent inhibitor of cellular respiration and a weak [[calcium antagonist]].
*Following an oral overdose of 15 g, [[metabolic acidosis]] with [[hyperventilation]], [[hyperglycemia]], and [[hypokalemia]] have been reported. No information on toxic serum concentrations is available.
*Following intravenous overdosing in animals, [[seizures]], [[tachyarrhythmias]], and [[ventricular fibrillation]] have been reported.  The oral median lethal dose in rats is 360 mg/kg.
 
=====Management =====
*To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual [[drug kinetics]] in your patient.
*No specific antidote is known.
*Treatment should be [[symptomatic and supportive]].
*Protect the patient’s airway and support [[ventilation]] and [[perfusion]]. Meticulously monitor vital signs, [[blood gases]], blood chemistry values, and other variables.
 
*If convulsions occur, consider [[diazepam]], [[phenytoin]], or [[phenobarbital]]. If the [[seizures]] are refractory, general [[anesthesia]] with [[thiopental]] or [[halothane]] and [[paralysis]] with a [[neuromuscular blocking agent]] may be necessary.
 
*For [[hypotension]], consider intravenous fluids, elevation of the legs, and an [[inotropic vasopressor]], such as [[dopamine]] or [[norepinephrine]] ([[levarterenol]]). Theoretically, [[calcium gluconate]] may be helpful in treating some of the toxic cardiovascular effects of papaverine; monitor the [[ECG]] and [[plasma calcium]] concentrations.
 
*Forced [[diuresis]], [[peritoneal dialysis]], [[hemodialysis]], or charcoal [[hemoperfusion]] have not been established as beneficial for an overdose of papaverine hydrochloride.
<!--Pharmacology-->
 
<!--Drug box 2-->
|drugBox=[[File:Papaverine 04.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
|mechAction=*The most characteristic effect of papaverine is relaxation of the tonus of all smooth muscle, especially when it has been spasmodically contracted. Papaverine Hydrochloride apparently acts directly on the muscle itself. This relaxation is noted in the vascular system and bronchial musculature and in the gastrointestinal, biliary and urinary tracts.
 
*The main actions of papaverine are exerted on cardiac and smooth muscle. Papaverine relaxes various [[smooth muscle]]s, especially those of larger [[arteries]]; this relaxation may be prominent if spasm exists. The antispasmodic effect is a direct one and unrelated to muscle innervation, and the muscle still responds to drugs and other stimuli causing contraction.  Papaverine has minimal actions on the central nervous system, although very large doses tend to produce some sedation and sleepiness in some patients. In certain circumstances, mild respiratory stimulation can be observed, but this is therapeutically inconsequential. Papaverine stimulates respiration by acting on carotid and aortic body [[chemoreceptor]]s.
 
*Papaverine relaxes the smooth musculature of the larger blood vessels, including the coronary, cerebral, peripheral, and pulmonary arteries. This action is particularly evident when such vessels are in spasm, induced reflexly or by drugs, and it provides the basis for the clinical use of papaverine in peripheral or pulmonary [[arterial embolism]].
 
*Experimentally in dogs, the alkaloid has been shown to cause fairly marked and long-lasting coronary [[vasodilatation]] and an increase in coronary blood flow. However, it also appears to have a direct [[inotropic]] effect and, when increased mechanical activity coincides with decreased systemic pressure, increases in coronary blood flow may not be sufficient to prevent brief periods of hypoxic [[myocardial depression]].
 
 
<!--Structure-->
|structure=* Papaverine Hydrochloride, USP, is the hydrochloride of an alkaloid obtained from opium or prepared synthetically. It belongs to the [[benzylisoquinoline]] group of alkaloids. It does not contain a [[phenanthrene]] group as do [[morphine]] and [[codeine]].
 
*Papaverine Hydrochloride, USP, is 6,7-dimethoxy-1- veratrylisoquinoline hydrochloride and contains, on the dried basis, not less than 98.5% of C20H21NO4•HCI. The molecular weight is 375.85. The structural formula is as shown.
 
[[File:Papaverine 01.png|thumb|none|400px|This image is provided by the National Library of Medicine.]]
 
*Papaverine Hydrochloride occurs as white crystals or white [[crystalline powder]]. One gram dissolves in about 30 mL of water and in 120 mL of alcohol. It is soluble in chloroform and practically insoluble in ether.
 
*Papaverine Hydrochloride Injection, USP, is a clear, colorless to pale-yellow solution.
 
*Papaverine Hydrochloride, for parenteral administration, is a smooth-muscle relaxant that is available in vials containing 30 mg/mL. Each vial also contains edetate disodium 0.005%. The 10 mL vials also contain [[chlorobutanol]] 0.5% as a preservative. pH may be adjusted with [[sodium citrate]] and/or [[citric acid]].
 
<!--Pharmacodynamics-->
|PD=There is limited information regarding <i>Pharmacodynamics</i> of Papaverine in the drug label.
 
<!--Pharmacokinetics-->
|PK=*Papaverine is effective by all routes of administration. A considerable fraction of the drug localizes in fat deposits and in the liver, with the remainder being distributed throughout the body. *It is metabolized in the liver. About 90% of the drug is bound to [[plasma protein]]. Although estimates of its biologic [[half-life]] vary widely, reasonably constant plasma levels can be maintained with oral administration at 6 hour intervals. The drug is excreted in the urine in an inactive form.
 
 
<!--Nonclinical Toxicology-->
|nonClinToxic=There is limited information regarding <i>Nonclinical Toxicology</i> of Papaverine in the drug label.
 
<!--Clinical Studies-->
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of Papaverine in the drug label.
 
<!--How Supplied-->
|howSupplied=* Papaverine Hydrochloride Injection, USP, 30 mg/mL
 
:*0517-4002-25              2 mL Vial                                packaged in boxes of 25
:*0517-4010-01              10 mL Multiple Dose Vial*    packaged individually
 
:*The 10 mL Multiple Dose Vial contains [[chlorobutanol]] 0.5% as a preservative.


'''Papaverine''' is an [[opium]] [[alkaloid]] used primarily in the treatment of visceral [[spasm]], [[vasospasm]] (especially those involving the [[heart]] and the [[brain]]), and occasionally in the treatment of [[erectile dysfunction]].{{ref_label|3|3|e}} While it is found in the [[opium poppy]], papaverine differs in both structure and pharmacological action from the other opium alkaloids ([[opiates]]).
<!--Patient Counseling Information-->
== Uses ==
|storage=*Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) (See USP Controlled Room Temperature).
Papaverine is approved to treat spasms of the gastointestinal tract, [[bile duct]]s and [[ureter]] and for use as a [[cerebral]] and [[coronary]] [[vasodilator]]{{ref_label|3|3|f}} in [[subarachnoid hemorrhage]] (combined with [[balloon angioplasty]]){{ref_label|6|6|a}} and [[coronary artery bypass surgery]].{{ref_label|7|7|a}} Papaverine may also be used as a smooth muscle relaxant in [[microsurgery]] where it is applied directly to blood vessels.
*PROTECT FROM LIGHT. RETAIN IN CARTON UNTIL TIME OF USE.
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of Papaverine in the drug label.


The in vivo mechanism of action is not entirely clear, but an inhibition of the [[enzyme]] phosphodiesterase causing elevation of cyclic AMP levels is significant.  It may also alter [[mitochondria]]l [[Cellular respiration|respiration]].
<!--Precautions with Alcohol-->
|alcohol=* Alcohol-Papaverine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.


It is also commonly used in [[cryopreservation]] of [[blood vessels]] along with other glycosaminoglycans and protein suspensions.<ref>E. Müller-Schweinitzer and P. Ellis: "Sucrose promotes the functional activity of blood vessels after cryopreservation in DMSO-containing fetal calf serum". Naunyn-Schmiedeberg's Archives of Pharmacology, Volume 345, Number 5 / May, 1992</ref><ref>Muller-Schweinitzer E, Hasse J, Swoboda L. : "Cryopreservation of human bronchi.". J Asthma. 1993;30(6):451-7. Links
<!--Brand Names-->
</ref> Functions as a [[vasodilator]] during cryopreservation when used in conjunction with [[verapamil]], [[phentolamine]], [[nifedipine]], tolazolines, or [[nitroprusside]].<ref>Brockbank KG.: "Effects of cryopreservation upon vein function in vivo". Cryobiology. 1994 Feb;31(1):71-81</ref><ref>Joseph S. Giglia, Jeremy D. Ollerenshaw, Patti E. Dawson, Kirby S. Black, William M. Abbott : "Cryopreservation Prevents Arterial Allograft Dilation ". Annals of Vascular Surgery Volume 16, Number 6 / December, 2002</ref>
|brandNames=*Papacon
*Para-Time S.R.
*Pavacot
<!--Look-Alike Drug Names-->
|lookAlike=* A® — B®<ref name="www.ismp.org">{{Cite web  | last =  | first =  | title = http://www.ismp.org | url = http://www.ismp.org | publisher =  | date =  }}</ref>


Papaverine is also being investigated as a topical growth factor in tissue expansion with some success.<ref>{{cite journal |author=Tang Y, Luan J, Zhang X |title=Accelerating tissue expansion by application of topical papaverine cream |journal=Plast. Reconstr. Surg. |volume=114 |issue=5 |pages=1166–9 |year=2004 |pmid=15457029}}</ref>
<!--Drug Shortage Status-->
|drugShortage=
}}
{{PillImage
|fileName=No image.jpg
}}
{{LabelImage
|fileName=Papaverine 02.png
}}
{{LabelImage
|fileName=Papaverine 03.png
}}
<!--Pill Image-->


== Side effects ==
Frequent side effects of papaverine treatment include polymorphic [[ventricular tachycardia]], constipation, interference with [[sulphobromophthalein]]{{ref_label|8|8|a}} [[retention test]] (used to determine hepatic function), increased [[transaminase]] levels, increased [[alkaline phosphatase]] levels, [[somnolence]], and [[Vertigo (medical)|vertigo]].{{ref_label|3|3|g}}


Rare side effects include flushing of the face, [[hyperhidrosis]] (excessive sweating), [[cutaneous eruption]], arterial [[hypotension]], tachycardia, lack of appetite, [[jaundice]], [[eosinophilia]], [[thrombopenia]], mixed [[hepatitis]], headache, allergic reaction, chronic active hepatitis,{{ref_label|3|3|h}} and paradoxical aggravation of cerebral vasospasm.{{ref_label|9|9|a}}


== Formulations and trade names==
<!--Label Display Image-->
Papaverine is available as a [[Conjugated system|conjugate]] of [[hydrochloride]], [[pyridoxal phosphate|codecarboxylate]], [[adenosine monophosphate|adenylate]], and [[teprosylate]].{{ref_label|10|10|a}} It was also once available as a salt of [[hydrobromide]], [[camphorsulfonic acid|camsylate]], [[cromesilate]], [[nicotinic acid|nicotinate]], and [[amygdalic acid|phenylglycolate]]. The hydrochloride salt is available for intramuscular, intravenous, rectal and oral administration.{{ref_label|5|5|b}} The teprosylate is available in intravenous, intramuscular, and orally administered formulations.{{ref_label|11|11|a}} The codecarboxylate is available in oral form, only,{{ref_label|12|12|a}} as is the adenylate.{{ref_label|13|13|a}}


The codecarboxylate is sold under the name Albatran®,{{ref_label|14|14|a}} the adenylate as Dicertan®,{{ref_label|15|15|a}} and the hydrochloride salt is sold variously as Artegodan® (Germany), Cardioverina® (countries outside Europe and the United States), Dispamil® (countries outside Europe and the United States), Opdensit® (Germany), Panergon® (Germany), Paverina Houde® (Italy, Belgium), Pavacap (United States), Pavadyl® (United States), Papaverin-Hamelin® (Germany), Paveron® (Germany), Spasmo-Nit® (Germany),{{ref_label|5|5|c}} Cardiospan®, Papaversan®, Cepaverin®, Cerespan®, Drapavel®, Forpaven®, Papalease®, Pavatest®, Paverolan®, Therapav® (France{{ref_label|16|16|a}}), Vasospan®, Cerebid®, Delapav®, Dilaves®, Durapav®, Dynovas®, Optenyl®, Pameion®, Papacon®, Pavabid®, Pavacen®, Pavakey®, Pavased®, Pavnell®, Alapav®, Myobid®, Vasal®, Pamelon®, Pavadel®, Pavagen®, Ro-Papav®, Vaso-Pav®, Papanerin-hcl®, Qua bid®, Papital T.R.®, Paptial T.R.®, Pap-Kaps-150®.{{ref_label|17|17|a}}


==References==
{{Reflist}}
<div class="references-small">
# {{note_label|1|1|a}} {{note_label|1|1|b}} {{note_label|1|1|c}} {{cite web | url=http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=544606 | title=SID 544606 -- PubChem Substance Summary | accessdate=25 September | accessyear=2005 }} National Center for Biotechnology Information.
# {{note_label|2|2|a}} {{cite web | url=http://bulkpharm.mallinckrodt.com/_attachments/msds/PAPVN.htm | title=Papaverine Material Safety Data Sheet | accessdate=25 September | accessyear=2005 }}
# {{note_label|3|3|a}} {{note_label|3|3|b}} {{note_label|3|3|c}} {{note_label|3|3|d}} {{note_label|3|3|e}} {{note_label|3|3|f}} {{note_label|3|3|g}} {{note_label|3|3|h}} {{cite web | | author=Unknown |
year=2000 | title=PAPAVERINE | work=Molécule(s) de base : PAPAVERINE | publisher=Biam | url=http://www.biam2.org/www/Sub3015.html | accessdate=25 September | accessyear=2005}} (French)
# {{note_label|4|4|a}} {{cite web | author=Unknown | year=2004 | title=Who should not take papaverine? | work=papaverine Consumer Drug Information | publisher=Cerner Multum, Inc | url=http://www.drugs.com/MTM/papaverine.html | accessdate=26 September | accessyear=2005}}
# {{note_label|5|5|a}} {{note_label|5|5|b}} {{note_label|5|5|c}} {{cite web | author=Unknown |
year=1999 | title=PAPAVERINE CHLORHYDRATE | work=Molécule(s) de base : PAPAVERINE | publisher=Biam | url=http://www.biam2.org/www/Sub65.html | accessdate=25 September | accessyear=2005}} (French)
# {{note_label|6|6|a}} {{cite journal | author=Liu, James K.; Couldwell, William T | title=Intra-arterial papaverine infusions for the treatment of cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage | journal=Neurocritical Care | volume=2 | issue=2 | year=2005 | pages=124-32 | id=PMID 16159054}} [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=16159054&dopt=ExternalLink Fulltext options] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=16159054&dopt=ExternalLink&ExternalLink=libs List of Library Holdings]
# {{note_label|7|7|a}} {{cite journal | author=Takeuchi K, Sakamoto S, Nagayoshi Y, Nishizawa H, Matsubara J | title=Reactivity of the human internal thoracic artery to vasodilators in coronary artery bypass grafting | journal=European Journal of Cardio-Thoracic Surgery | volume=26 | issue=5 | year=2004 | pages=956-9 | id=PMID 15519189}} [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=15519189&dopt=ExternalLink Fulltext options] [http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&list_uids=15519189&dopt=ExternalLink&ExternalLink=libs List of Library Holdings]
# {{note_label|8|8|a}} {{cite web | url=http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=149219 | title=SID 149219 -- PubChem Substance Summary | accessdate=26 September | accessyear=2005 }} National Center for Biotechnology Information.
# {{note_label|9|9|a}} {{cite journal | author=Clyde BL, Firlik AD, Kaufmann AM, Spearman MP, Yonas H | title=Paradoxical aggravation of vasospasm with papaverine infusion following aneurysmal subarachnoid hemorrhage. Case report | journal=Journal of Neurosurgery | volume=84 | issue=4 | year=1996 | pages=690-5}} {{PMID|8613866}}
# {{note_label|10|10|a}} {{cite web | url=http://www.biam2.org/www/Gsu1575.html | title=Molécule de base : PAPAVERINE | accessdate=26 September | accessyear=2005 }} ''Biam.''
# {{note_label|11|11|a}} {{cite web | author=Unknown |
year=1999 | title=PAPAVERINE TEPROSILATE | work=Molécule(s) de base : PAPAVERINE | publisher=Biam | url=http://www.biam2.org/www/Sub70.html | accessdate=26 September | accessyear=2005}} (French)
# {{note_label|12|12|a}} {{cite web | author=Unknown | year=1998 | title=PAPAVERINE CODECARBOXYLATE | work=Molécule(s) de base : PAPAVERINE | publisher=Biam | url=http://www.biam2.org/www/Sub1293.html | accessdate=26 September | accessyear=2005}} (French)
# {{note_label|13|13|a}} {{cite web | author=Unknown | year=1998 | title=PAPAVERINE ADENYLATE | work=Molécule(s) de base : PAPAVERINE | publisher=Biam | url=http://www.biam2.org/www/Sub1295.html | accessdate=26 September | accessyear=2005}} (French)
# {{note_label|14|14|a}} {{cite web | url=http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=660773 | title=SID 660773 PubChem Substance Summary | accessdate=25 September | accessyear=2005 }} National Center for Biotechnology Information.
# {{note_label|15|15|a}} {{cite web | url=http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=660767 | title=SID 660767 -- PubChem Substance Summary | accessdate=25 September | accessyear=2005 }} National Center for Biotechnology Information.
# {{note_label|16|16|a}} {{cite web | url=http://www.reptox.csst.qc.ca/Produit.asp?no_produit=108688&nom=THERAPAV+(PRODUIT+PUR)&incr=0 | title=THERAPAV (PRODUIT PUR) - Détail | accessdate=26 September | accessyear=2005 }} CSST - Service du répertoire toxicologique. (French)
# {{note_label|17|17|a}} {{cite web | url=http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=40460&ncount=61#Synonyms | title=SID 660767 -- PubChem Substance Summary - Depositor-Supplied Synonyms: All | accessdate=26 September | accessyear=2005 }} National Center for Biotechnology Information.
</div>


{{Drugs for functional gastrointestinal disorders}}
{{Urologicals}}
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[[Category:Natural opium alkaloids]]
[[Category:Vasodilators]]
[[Category:Drugs]]


[[pl:Papaweryna]]
<!--Category-->
[[de:Papaverin]]
[[eo:Papaverino]]
[[fr:Papavérine]]
[[ja:パパベリン]]
[[ru:Папаверин]]
[[sk:Papaverín]]
[[sv:Papaverin]]


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Latest revision as of 17:05, 19 January 2015

Papaverine
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aparna Vuppala, M.B.B.S. [2]

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Overview

Papaverine is a phosphodiesterase inhibitor that is FDA approved for the treatment of vascular spasm associated with acute myocardial infarction (coronary occlusion), angina pectoris, peripheral vascular disease, peripheral and pulmonary embolism. Common adverse reactions include general discomfort, nausea, abdominal discomfort, anorexia, skin rash, malaise, vertigo and headache..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

  • Papaverine Hydrochloride may be administered intravenously or intramuscularly. The intravenous route is recommended when an immediate effect is desired, but the drug must be injected slowly over the course of 1 or 2 minutes to avoid uncomfortable or alarming side effects.
  • Parenteral administration of papaverine hydrochloride in doses of 1 to 4 mL is repeated every 3 hours as indicated. In the treatment of cardiac extrasystoles, 2 doses may be given 10 minutes apart.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Papaverine in adult patients.


Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

Safety and effectiveness in children have not been established.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Papaverine in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Papaverine in pediatric patients.

Contraindications

Complete atrioventricular heart block
Impotence

Warnings

Precautions

  • Papaverine Hydrochloride Injection, USP, should not be added to Lactated Ringer’s Injection, because precipitation would result.
  • Papaverine Hydrochloride should be used with caution in patients with glaucoma. The medication should be discontinued if hepatic hypersensitivity with gastrointestinal symptoms, jaundice, or eosinophilia becomes evident or if liver function test values become altered.
  • Drug dependence resulting from the abuse of many of the selective depressants, including papaverine hydrochloride, has been reported.

Adverse Reactions

Clinical Trials Experience

  • Hepatitis, probably related to an immune mechanism, has been reported infrequently. Rarely, this has progressed to cirrhosis.

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Papaverine in the drug label.

Drug Interactions

There is limited information regarding Papaverine Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): C

  • No teratogenic effects were observed in rats when papaverine hydrochloride was administered subcutaneously as a single agent. It is not known whether papaverine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. *Papaverine Hydrochloride should be given to a pregnant woman only if clearly needed.


Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Papaverine in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Papaverine during labor and delivery.

Nursing Mothers

  • It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when papaverine hydrochloride is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in children have not been established.

Geriatic Use

There is no FDA guidance on the use of Papaverine with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Papaverine with respect to specific gender populations.

Race

There is no FDA guidance on the use of Papaverine with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Papaverine in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Papaverine in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Papaverine in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Papaverine in patients who are immunocompromised.

Administration and Monitoring

Administration

  • Intravenously or Intramuscularly

Monitoring

There is limited information regarding Monitoring of Papaverine in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Papaverine in the drug label.

Overdosage

Signs and Symptoms
Management
  • To obtain up-to-date information about the treatment of overdose, a good resource is your certified Regional Poison Control Center. In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient.
  • No specific antidote is known.
  • Treatment should be symptomatic and supportive.
  • Protect the patient’s airway and support ventilation and perfusion. Meticulously monitor vital signs, blood gases, blood chemistry values, and other variables.

Pharmacology

This image is provided by the National Library of Medicine.

Mechanism of Action

  • The most characteristic effect of papaverine is relaxation of the tonus of all smooth muscle, especially when it has been spasmodically contracted. Papaverine Hydrochloride apparently acts directly on the muscle itself. This relaxation is noted in the vascular system and bronchial musculature and in the gastrointestinal, biliary and urinary tracts.
  • The main actions of papaverine are exerted on cardiac and smooth muscle. Papaverine relaxes various smooth muscles, especially those of larger arteries; this relaxation may be prominent if spasm exists. The antispasmodic effect is a direct one and unrelated to muscle innervation, and the muscle still responds to drugs and other stimuli causing contraction. Papaverine has minimal actions on the central nervous system, although very large doses tend to produce some sedation and sleepiness in some patients. In certain circumstances, mild respiratory stimulation can be observed, but this is therapeutically inconsequential. Papaverine stimulates respiration by acting on carotid and aortic body chemoreceptors.
  • Papaverine relaxes the smooth musculature of the larger blood vessels, including the coronary, cerebral, peripheral, and pulmonary arteries. This action is particularly evident when such vessels are in spasm, induced reflexly or by drugs, and it provides the basis for the clinical use of papaverine in peripheral or pulmonary arterial embolism.
  • Experimentally in dogs, the alkaloid has been shown to cause fairly marked and long-lasting coronary vasodilatation and an increase in coronary blood flow. However, it also appears to have a direct inotropic effect and, when increased mechanical activity coincides with decreased systemic pressure, increases in coronary blood flow may not be sufficient to prevent brief periods of hypoxic myocardial depression.

Structure

  • Papaverine Hydrochloride, USP, is the hydrochloride of an alkaloid obtained from opium or prepared synthetically. It belongs to the benzylisoquinoline group of alkaloids. It does not contain a phenanthrene group as do morphine and codeine.
  • Papaverine Hydrochloride, USP, is 6,7-dimethoxy-1- veratrylisoquinoline hydrochloride and contains, on the dried basis, not less than 98.5% of C20H21NO4•HCI. The molecular weight is 375.85. The structural formula is as shown.
This image is provided by the National Library of Medicine.
  • Papaverine Hydrochloride occurs as white crystals or white crystalline powder. One gram dissolves in about 30 mL of water and in 120 mL of alcohol. It is soluble in chloroform and practically insoluble in ether.
  • Papaverine Hydrochloride Injection, USP, is a clear, colorless to pale-yellow solution.
  • Papaverine Hydrochloride, for parenteral administration, is a smooth-muscle relaxant that is available in vials containing 30 mg/mL. Each vial also contains edetate disodium 0.005%. The 10 mL vials also contain chlorobutanol 0.5% as a preservative. pH may be adjusted with sodium citrate and/or citric acid.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Papaverine in the drug label.

Pharmacokinetics

  • Papaverine is effective by all routes of administration. A considerable fraction of the drug localizes in fat deposits and in the liver, with the remainder being distributed throughout the body. *It is metabolized in the liver. About 90% of the drug is bound to plasma protein. Although estimates of its biologic half-life vary widely, reasonably constant plasma levels can be maintained with oral administration at 6 hour intervals. The drug is excreted in the urine in an inactive form.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Papaverine in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Papaverine in the drug label.

How Supplied

  • Papaverine Hydrochloride Injection, USP, 30 mg/mL
  • 0517-4002-25 2 mL Vial packaged in boxes of 25
  • 0517-4010-01 10 mL Multiple Dose Vial* packaged individually
  • The 10 mL Multiple Dose Vial contains chlorobutanol 0.5% as a preservative.

Storage

  • Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) (See USP Controlled Room Temperature).
  • PROTECT FROM LIGHT. RETAIN IN CARTON UNTIL TIME OF USE.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Papaverine in the drug label.

Precautions with Alcohol

  • Alcohol-Papaverine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

  • Papacon
  • Para-Time S.R.
  • Pavacot

Look-Alike Drug Names

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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