Papaverine Injection B.P.

20 mg/ml, 50 mg/ml, 100 mg/3 ml


For the use of a Registered Medical Practitioner or a Hospital or a Institution only. 

Vascular spasm associated with acute myocardial infarction (coronary occlusion), angina pectoris, peripheral and pulmonary embolism
Peripheral vascular disease
Cerebral angiospastic states
Visceral spasm (e.g., ureteral, biliary, or gastrointestinal colic)

PAPAVERINE INJECTION (Papaverine Hydrochloride) is a peripheral vasodilator. Chemically, Papaverine Hydrochloride is 1-(3,4-Dimethoxybenzyl)-6,7-dimethoxyisoquinoline hydrochloride. The molecular formula is C20H21NO4, HCl and molecular weight is 375.90.

Its structural formula is :

Papaverine Injection B.P.


PAPAVERINE  INJECTION is a sterile, nonpyrogenic, clear colourless to pale yellow solution, filled in amber ampoule of suitable size.


1) Each ml contains :
     Papaverine Hydrochloride B.P.               20 mg
     Water for Injections B.P.                             q.s.

2) Each ml contains :
     Papaverine Hydrochloride B.P.               30 mg
     Water for Injections B.P.                             q.s.

3) Each ml contains :
     Papaverine Hydrochloride B.P.               50 mg
     Water for Injections B.P.                             q.s.

4) Each 3 ml contains :
     Papaverine Hydrochloride B.P.               100 mg
     Water for Injections B.P.                             q.s.

Papaverine hydrochloride directly relaxes tone of all smooth muscle, especially when spasmodically contracted. It causes vasodilatation of blood vessels of the coronary, cerebral, pulmonary and peripheral arteries; relaxes musculature of bronchi, GI tract, ureters and biliary system.

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. The extent and time-course of papaverine absorption have not been documented. In theory, systemic absorption following intracavernosal injection would initially be rapid, until the local effect of papaverine led to occlusion of the venous outflow from the penis. Absorption would then be slow, but would pick up again as detumescence occurred and the sequestered blood was returned to the systemic circulation. After intracavernosal injection, the peak plasma concentration is several times lower than after extracavernosal injection. 

PAPAVERINE  INJECTION indicated in 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 (e.g., ureteral, biliary, or gastrointestinal colic) and in treatment of  erection dysfunction. 


Administration :
PAPAVERINE  INJECTION may be administered by intravenous, intramuscular, or intra-arterial route. The intra-arterial route should be used only by those experienced in the procedure. Intravenous administration may be used when an immediate effect is desired, but should be done slowly over 1 or 2 minutes to avoid adverse effects (arrhythmias and fatal apnoea). 

PAPAVERINE  INJECTION should only be prescribed, and treatment should be supervised, by prescribers having expertise in the management of erectile dysfunction using a range of treatment modalities. The use of PAPAVERINE  INJECTION in combination with other agents, including phentolamine and alprostadil is not recommended. PAPAVERINE  INJECTION should be administered by intracavernosal injection for treatment of erectile dysfunction. Before initiation of treatment with PAPAVERINE  INJECTION patients should be carefully assessed by a specialist practitioner in erectile dysfunction with appropriate training in the use of this drug. The dose should be titrated carefully according to individual need. The first injection of PAPAVERINE  INJECTION must be done by medically trained personnel. After proper training and instruction, PAPAVERINE  INJECTION may be injected at home. If self-administration is planned, the specialist should make an assessment of the patient’s (or as appropriate, the partner’s) skill and competence with the procedure. While on self-injection treatment, it is recommended that the patient visit the specialist’s office at periodic intervals. At that time, the efficacy and safety of the therapy should be assessed, and the dose of PAPAVERINE  INJECTION should be adjusted, if needed. 

The ampoule used in this product is equipped with O.P.C (One Point Cut) opening system. No ampoule file is needed to open the ampoule. The neck of the ampoule is prescored at the point of constriction. A coloured dot on the ampoule head helps to orientate the ampoule. Take the ampoule and face the coloured dot. Let the solution at the head of the ampoule to flow down by shaking or a gentle stroke. The ampoule opens easily by placing the thumb on the coloured dot and gently pressing downwards as shown.

Ampoules equipped with One Point Cut (OPC) technology

Dosage :
Usual adult dose 
Vasospastic therapy adjunct :
Intra-arterial, 40 mg, administered slowly over a one to two minute period. Intramuscular or intravenous, 30 to 120 mg every three hours, administered slowly over a one to two minute period. In the treatment of cardiac asystole, two doses may be given ten minutes apart.

The lowest effective dose should be determined for each patient. In general most patients respond to doses in the range of 2.5 to 60 mg of papaverine. A starting dose of 15 mg is recommended for patients with erectile dysfunction due to most causes. Patients with psychogenic erectile dysfunction are likely to respond to lower doses, while those with vasculogenic erectile dysfunction are likely to require higher doses. Patients who do not respond to a dose of 60 mg should be changed to alternative therapy. A starting dose of 5 mg is recommended for men with erectile dysfunction due to spinal cord injury. Erection usually occurs within 10 minutes of injection of the drug and may persist for one to several hours. Tolerance to papaverine may occur during long-term use and may require an increase in dosage. The dose should be reduced if erections persist for longer than four hours. Early studies using doses of up to 80 mg papaverine resulted in high proportion patients requiring assisted detumescence. Dosage adjustment should be made carefully, based on the degree and duration of tumescence achieved with the previous dose. 

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.
PAPAVERINE  INJECTION is contraindicated in patients who have conditions that might predispose them to priapism such as sickle cell anaemia, multiple myeloma or leukaemia. Patients with pre-existing penile fibrosis should not be accepted into intracavernosal self-injection therapy. PAPAVERINE  INJECTION should not be used in patients with anatomical deformation of the penis, such as angulation, cavernosal fibrosis or Peyronie’s disease. PAPAVERINE  INJECTION should not be used in men for whom sexual activity is inadvisable or contraindicated. PAPAVERINE  INJECTION should not be used in patients with penile implants. 

PAPAVERINE  INJECTION should not be added to Lactated Ringer’s Injection, because precipitation would result. PAPAVERINE  INJECTION 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.

Intracavernosal injection of PAPAVERINE  INJECTION has caused priapism. Treatment of priapism should not be delayed. Patients should be instructed to seek urgent medical attention if an erection lasts for more than four hours. Priapism has been managed by aspiration of cavernosal blood and/or intracavernosal injection of small doses of an á-adrenergic agonist. Parenteral administration of high doses may cause cardiac arrhythmia and fatal apnoea; a slow rate of intravenous administration is recommended (over a 1 to 2 minute period) to avoid serious adverse effects. 

Penile Fibrosis 
Patients should be carefully assessed for pre-existing penile fibrosis before initiation of treatment with intracavernosal PAPAVERINE  INJECTION  If pre-existing penile fibrosis is found, the patient should not be accepted into intracavernosal self-injection therapy. This assessment should be made during pharmacologically-induced erection. At regular visits, the physician must examine the penis carefully, preferably in the erect state, for potential development of fibrotic changes. If there are signs of fibrotic complications, treatment with PAPAVERINE  INJECTION must be stopped immediately. Development of penile fibrosis appears to be related to the injection volume being in excess of 1 ml. During self-injection therapy, the patient must be instructed to report to the physician any unusual new adverse effects such as increased or new penile pain, penile bending and/or nodule formation in the penile shaft. 

Other Precautions 
Caution is also advised in the presence of cardiac conduction disorders or unstable cardiovascular disease. Extreme care should be taken when conduction is depressed since the drug may produce transient ectopic rhythms of ventricular origin, either premature  beats or paroxysmal tachycardia. Elderly patients should undertake an ECG before being prescribed this product to eliminate the existence of cardiac conduction disorders. Patients on anticoagulants such as warfarin or heparin may have an increased propensity for bleeding after the intracavernosal injection. The injection of papaverine can induce a small amount of bleeding at the site of injection. In patients infected with blood-borne diseases, this could increase the transmission of such diseases to the partner. Patients should be advised to take care when getting up from a lying or sitting position or when climbing stairs because of the possibility of postural hypotension. 

Combination Therapy 
The physical compatibility and stability of papaverine with alprostadil and/or phentolamine in mixed preparations has not been established. Co-administration of papaverine with alprostadil and/or phentolamine was associated with an increased risk of adverse events including dizziness and syncope in evaluated trials. The safety and efficacy of combination therapy with papaverine and phentolamine and/or alprostadil has not been established. The use of papaverine in combination with oral agents for erectile dysfunction has not been established. 


Pregnancy : Category 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 foetal 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.

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.

Paediatric Use :
Safety and effectiveness in children have not been established.

Geriatrics : 
Appropriate studies on the relationship of age to the effects of papaverine have not been performed in the geriatric population. However, the risk of papaverine-induced hypothermia may be increased in elderly patients when used in erectile dysfunction.

The effects of PAPAVERINE  INJECTION may be slightly potentiated by CNS depressants and a synergism may result from combination with morphine. Papaverine may interfere with the therapeutic effects of levodopa in patients with Parkinson’s disease when the drugs are administered concomitantly. Several Parkinsonian patients maintained on levodopa have developed worsening of their Parkinsonism following PAPAVERINE  INJECTION administration. The therapeutic response to levodopa returned 5 to 10 days after the PAPAVERINE  INJECTION was stopped. The use of PAPAVERINE  INJECTION in these patients should be avoided.

Patients on anticoagulants such as warfarin or heparin may have an increased propensity for bleeding after the intracavernosal injection. Ioxaglate can form a paste-like precipitate with papaverine, and this could have serious consequences should precipitation occur in the penis. 

Effect on Laboratory Tests :
Liver function test results (serum ALT, AST and bilirubin concentrations as well as eosinophil count) may be altered during intravenous papaverine therapy.

Cardiovascular : Increase in heart rate, slight increase in BP.
CNS : Depression, dizziness, vertigo, headache, drowsiness, sedation, lassitude, malaise, lethargy.
Dermatological : Flushing of face, sweating, pruritus.
Gastrointestinal : Constipation, nausea, diarrhoea, abdominal distress, dry mouth, anorexia.
Hepatic : Jaundice, hepatitis.
Haematological : Eosinophilia.
Respiratory : Increased depth of respiration.

Local Adverse Events 
•  Prolonged erection/priapism 
•  Penile fibrosis, manifested as subcutaneous nodules,  plaques, cavernosal fibrosis, scarring, deformity, curvature (Peyronie’s disease) and calcification 
•  Pain/ discomfort/ burning sensations during the injection 
•  Injection site bruising/ haematoma 
•  Injection site blister/ ulcer 
•  Penile/ foreskin oedema 
•  Loss of penile sensation 
•  Misplaced injections, sometimes leading to urethral  bleeding 
•  Pain during erection 
•  Infection/ cavernositis/ pyogenic granuloma 
•  Thrombophlebitis/ lymphangitis 
•  Intracorporal needle breakage 
•  Fixed drug eruption 
•  Penile fracture 

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, hyperglycaemia, and hypokalemia have been reported. No information on toxic serum concentrations is available. Following intravenous overdosing in animals, seizures, tachyarrhythmia, and ventricular fibrillation have been reported.

In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in your patient. 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.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Store below 30ºC, protected from light. 
Do not refrigerate.

24 months from the date of manufacture.

PAPAVERINE  INJECTION is supplied as below :

20 mg/ml 1 ml Ampolue 10 Ampolues per box
30 mg/ml 1 ml Ampolue 10 Ampolues per box
50 mg/ml 2 ml Ampolue 5 Ampolues per box
100 mg/3ml 2 ml Ampolue 5 Ampolues per box


Disclaimer : For the use of a Registered Medical Practitioner or a Hospital or a Institution only. Also it is not intended to be used by healthcare professionals or patients for the purpose of prescribing or administering these products. Questions regarding the complete and current content of product labeling / specification / presentation should be directed to SGPharma.

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