Consumer medicine information

DBL Papaverine Hydrochloride Injection

Papaverine hydrochloride

BRAND INFORMATION

Brand name

DBL Papaverine Hydrochloride Injection USP

Active ingredient

Papaverine hydrochloride

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using DBL Papaverine Hydrochloride Injection.

What is in this leaflet

This leaflet answers some common questions about DBL Papaverine Hydrochloride Injection. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor weighed the risks of you using papaverine against the benefits they expect it will have for you.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet. You may need to read it again.

What DBL Papaverine Hydrochloride Injection is used for

This medicine is used to produce erections in impotent men.

It belongs to a group of medicines called vasodilators.

When papaverine is injected into the penis (called ‘intracavernosal’ injection) it works by increasing blood flow to the penis, which results in an erection.

Ask your doctor if you have any questions about why this product has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is not addictive.

This medicine is available only with a doctor’s prescription.

There is not enough information to recommend the use of this medicine for children and newborn babies.

Before you use DBL Papaverine Hydrochloride Injection

When you must not take it

Do not use DBL Papaverine Hydrochloride Injection if you have an allergy to:

  • any medicine containing papaverine
  • any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction may include shortness of breath, wheezing or difficulty breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin.

Do not use this medicine if you have any of the following medical conditions:

  • complete atrioventricular block (a heart condition characterised by a slow or irregular heart beat)
  • sickle cell anaemia (a disease in which the amount of oxygen-carrying pigment in the blood is below normal and the red blood cells become distorted)
  • leukaemia (cancer of the blood)
  • multiple myeloma (cancer of the bone)
  • an implant in your penis
  • any deformities of the penis
  • abnormal thickening of the tissue of the penis
  • any condition where sexual activity is inadvisable.

Do not use this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start using this medicine, talk to your doctor.

Before you start to use it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • heart problems
  • liver disease
  • any disease that may be transmitted by contact with blood.

Tell your doctor if you are taking any oral medications used to treat impotence in men.

If you have not told your doctor about any of the above, tell him/her before you start to use papaverine.

Taking other medicines

Tell your doctor or pharmacist if you are taking or using any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Some medicines and papaverine may interfere with each other. These include:

  • levodopa, a medicine used in the treatment of Parkinson’s disease
  • medicines to strong relieve pain, such as morphine, or other medicines which cause sleepiness
  • medicines used to prevent blood clots, such as warfarin and heparin
  • ioxaglate, a dye used when taking x-rays of the penis.

These medicines may be affected by papaverine, or may affect how well it works. You may need different amounts of your medicine, or you may need to take/use different medicines.

Your doctor and pharmacist may have more information on medicines to be careful with or avoid while using this medicine.

How DBL Papaverine Hydrochloride Injection is given

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

How much is given

Your doctor will decide what dose of papaverine you will receive. This depends on your medical condition and whether or not you are taking any other medicines.

How it is given

A doctor or nurse will show you how to do the injection for at least the first time. If you will be self-administering papaverine your doctor will provide you with proper training and instruction to ensure that administration related injuries do not occur.

It is important that you follow your doctor's instructions at all times. If you are not certain about the way this medicine is given please contact your doctor; this leaflet is only intended to remind you about the instructions your doctor has already given you.

Always use a new syringe and needle for each injection. A 13 mm 27 to 30 gauge needle is recommended.

If the needle is bent at any time, do not use it for injecting papaverine and do not attempt to straighten it before injecting papaverine. A bent or restraightened needle may be more likely to break. Needle breakage with a portion of the needle remaining in the penis has been reported and in some cases requires hospitalisation and surgical removal.

Do not use papaverine if the ampoule is damaged or if the solution looks cloudy, coloured, or has particles in it.

Stretch the penis out across the thigh. If you are uncircumcised the foreskin must be pulled back before you inject papaverine. Clean the injection area with an alcohol swab.

Papaverine is injected directly into the base of the penis on the left or right-hand side. It is given as a slow injection over 1 to 2 minutes. Papaverine should not be injected just under the skin or into the midline or lower part of the penis.

After you have completed the injection, put pressure on the place of injection to prevent bruising. Then massage your penis as instructed by your doctor. This helps the medicine spread to all parts of the penis, so that it will work better.

Do not re-use or share needles or syringes.

Papaverine normally begins to work in about 10 minutes and the erection may persist for one to several hours.

If you use too much (overdose)

In case of overdose, immediately contact the Poisons Information Centre for advice on 13 11 26, or go to Accident and Emergency at your nearest hospital, if you think that you or anyone else may have used too much papaverine. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of an overdose may include nausea, vomiting, weakness, drowsiness, double vision, rapid uncontrollable movements of the eyes, sweating, flushing, dizziness, increased heart rate or priapism (a persistent painful erection of the penis that does not reverse within four hours).

While you are using DBL Papaverine Hydrochloride Injection

Things you must do

Do not injection this medicine under the skin or into the midline or lower part of the penis.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are using papaverine.

Tell any other doctors, dentists, and pharmacists who are treating you that you are using this medicine.

If you are going to have surgery, tell the surgeon or anaesthetist that you are using this medicine. It may affect other medicines used during surgery.

If you are about to have any blood tests, tell your doctor that you are using this medicine. It may interfere with the results of some tests.

Contact your doctor immediately if the erection lasts for longer than 4 hours, or if it becomes painful. This may be a sign of priapism and must be treated immediately to prevent permanent damage.

Keep all of your doctor's appointments so that your progress can be checked.

Examine your penis regularly and contact your doctor if you notice changes or experience bleeding that does not stop despite applying pressure on the site. Things to look out for include a lump where papaverine has been injected, or your penis becoming curved. These may be signs of fibrosis (abnormal thickening of tissue).

Things you must not do

Do not use papaverine to treat any other complaint.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not increase the dosage of your medicine or use it more frequently than your doctor has instructed. If too much is used, the erection may become so strong that it lasts too long and does not reverse when it should.

Do not use any solution left in the ampoule for a second injection, it should be used on one occasion only. Discard any solution that is left over.

Do not use the needle to inject if it is bent.

Things to be careful of

Be careful driving or operating machinery until you know how papaverine affects you. This medicine may cause dizziness, and drowsiness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything that could be dangerous.

If you feel light-headed, dizzy or faint when getting out of bed or standing up, get up slowly. Standing up slowly, especially when you get up from bed or chairs, will help your body get used to the change in position and blood pressure. If this problem continues or gets worse, talk to your doctor.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using papaverine. This medicine helps most people with impotence, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • dizziness, headache or flushing
  • mild discomfort in the penis during injection
  • bruising or bleeding at injection site
  • blood appearing at the end of the penis
  • tingling at the tip of the penis
  • difficulty in ejaculating.

The above list of side effects are usually mild and short-lived.

Tell your doctor as soon as possible if you notice any of the following:

  • pain or burning along penis
  • redness and swelling at the injection site
  • fibrosis (lumps) in the penis
  • bending of the penis
  • blister or ulcer at injection site
  • swelling of the penis or foreskin.

The above list includes serious side effects which may require medical attention.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • increase in heart rate
  • erection that lasts for more than 4 hours
  • painful erection
  • yellowing of the eyes and/or skin (jaundice).

These are very serious side effects. You may need urgent medical attention or hospitalisation.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell. Other side effects not listed above may occur in some patients.

After using DBL Papaverine Hydrochloride Injection

Storage

Keep your medicine in the original pack until it is time to use it. If you take your medicine out of the pack it may not keep well.

Keep your medicine in a cool dry place where the temperature stays below 25C. Protect from light.

Do not store papaverine or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop using this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is leftover.

Product description

What it looks like

DBL Papaverine Hydrochloride Injection is a clear colourless to pale yellow solution in a glass ampoule.

Ingredients

Active ingredients:

  • papaverine hydrochloride

Other ingredients:

  • water for injections.

This medicine does not contain gluten, lactose, sucrose, tartrazine, or any other azo dyes.

Supplier / Sponsor

Australian Sponsor:

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizer.com.au

DBL Papaverine Hydrochloride Injection is available in 120 mg/10 mL ampoules (packs of 5) - AUST R 16277

This leaflet was updated in May 2021.

™ Trademark

© Pfizer Australia Pty Ltd 2021

Published by MIMS July 2021

BRAND INFORMATION

Brand name

DBL Papaverine Hydrochloride Injection USP

Active ingredient

Papaverine hydrochloride

Schedule

S4

 

1 Name of Medicine

Papaverine hydrochloride.

2 Qualitative and Quantitative Composition

DBL Papaverine Hydrochloride Injection is supplied in ampoules containing 120 mg/10 mL of papaverine hydrochloride BP in water for injection BP/USP.

3 Pharmaceutical Form

DBL Papaverine Hydrochloride Injection is a sterile, clear, colourless to pale-yellow solution of papaverine hydrochloride in water for injections.

4 Clinical Particulars

4.1 Therapeutic Indications

DBL Papaverine Hydrochloride Injection is indicated for the treatment of erectile dysfunction.

4.2 Dose and Method of Administration

Dosage.

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 hydrochloride.
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 hydrochloride 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 hydrochloride 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.

Method of administration.

DBL Papaverine Hydrochloride 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 DBL Papaverine Hydrochloride Injection in combination with other agents, including phentolamine and alprostadil is not recommended (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
DBL Papaverine Hydrochloride Injection should be administered by intracavernosal injection.
Ampoules of DBL Papaverine Hydrochloride Injection are intended for single use only and should be discarded after use.
Intracavernosal papaverine hydrochloride may be self-administered by patients, but only after careful training in the technique to reduce the incidence of inadvertent subcutaneous administration, ecchymosis and urethral injury.
The patient should be instructed to use a new syringe and needle for each injection and in the appropriate disposal of the syringe and the needle. Needle breakage, with a portion of the needle remaining in the penis, has been reported and in some cases, required hospitalisation and surgical removal. The patient should be cautioned against using bent needles, to inject DBL Papaverine Hydrochloride Injection or attempting to straighten a bent needle prior to injecting.
Following is the general procedure for injection.
1. Prior to administration, visually inspect DBL Papaverine Hydrochloride Injection for particulate matter and discolouration.
2. Using a needle, withdraw the required dosage. A 13 mm, 27 to 30 gauge needle is recommended.
3. Stretch the penis out across the thigh, with the foreskin retracted in uncircumcised men. Clean the site with an alcohol swab. Do not inject along the midline. Do not inject through any of the superficial veins that are clearly visible under the skin. Inject over one to two minutes into either of the two corpora cavernosa. Inject at 90 degrees to the skin; the needle should be inserted up to the needle hub to ensure that the corpus is injected.

Note.

Subsequent injections should be alternated between the two cavernosa. The injection site should be varied from the base of the penis to just proximal to the glans avoiding the midline and any veins. Injections should not be made into the underside of the penis.
4. After injecting, remove the needle and apply pressure to the injection site with the alcohol swab until any bleeding stops. The entire length of the corpus cavernosum should be squeezed firmly to distribute medication, followed by the same procedure on the other side. The penis should then be pinched transversely in several places to distribute medication to both ends of the corpus cavernosum. This procedure should result in an erection that is adequate for intercourse.

Dosage adjustments.

Before initiation of treatment with DBL Papaverine Hydrochloride 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 DBL Papaverine Hydrochloride Injection must be done by medically trained personnel. After proper training and instruction, DBL Papaverine Hydrochloride 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 DBL Papaverine Hydrochloride Injection should be adjusted, if needed.

4.3 Contraindications

DBL Papaverine Hydrochloride Injection is contraindicated in patients with complete atrioventricular block.
DBL Papaverine Hydrochloride 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. DBL Papaverine Hydrochloride Injection should not be used in patients with anatomical deformation of the penis, such as angulation, cavernosal fibrosis or Peyronie's disease.
DBL Papaverine Hydrochloride Injection should not be used in men for whom sexual activity is inadvisable or contraindicated.
DBL Papaverine Hydrochloride Injection should not be used in patients with penile implants.

4.4 Special Warnings and Precautions for Use

Priapism.

Intracavernosal injection of DBL Papaverine Hydrochloride 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 α-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 DBL Papaverine Hydrochloride 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 DBL Papaverine Hydrochloride 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.
Patients on anticoagulants such as warfarin or heparin may have an increased propensity for bleeding after the intracavernosal injection.
The injection of papaverine hydrochloride 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 use of papaverine hydrochloride in combination with oral agents for erectile dysfunction has not been established.
For combination therapy with alprostadil and/or phentolamine please see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

Use in hepatic impairment.

DBL Papaverine Hydrochloride Injection should be used with caution in patients with pre-existing hepatic impairment (liver disease) because of the potential for exacerbation. If signs or symptoms of exacerbated hepatic impairment occur during papaverine hydrochloride therapy, the drug should be discontinued.
Elevations of hepatic enzymes and bilirubin have been reported during use of papaverine hydrochloride. Most of the affected patients were also consuming alcohol and a causal relationship to papaverine hydrochloride has not been proven. Routine monitoring of hepatic function during papaverine hydrochloride therapy is not required. However, patients with a history of alcohol abuse or liver disease should be followed more closely with liver function tests obtained before initiating treatment and at 6-monthly intervals.

Use in the elderly.

Elderly patients should undertake an ECG before being prescribed this product to eliminate the existence of cardiac conduction disorders.

Paediatric use.

No data available.

Effects on laboratory tests.

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

4.5 Interactions with Other Medicines and Other Forms of Interactions

The effects of papaverine hydrochloride may be slightly potentiated by CNS depressants and a synergism may result from combination with morphine.
Papaverine hydrochloride 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 hydrochloride administration. The therapeutic response to levodopa returned 5 to 10 days after the papaverine hydrochloride was stopped. The use of papaverine hydrochloride 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 hydrochloride, and this could have serious consequences should precipitation occur in the penis.

Combination therapy.

The physical compatibility and stability of papaverine hydrochloride with alprostadil and/or phentolamine in mixed preparations has not been established. Coadministration of papaverine hydrochloride 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 hydrochloride and phentolamine and/or alprostadil has not been established.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no adequate human or animal studies addressing the effect of papaverine hydrochloride on fertility or reproductive performance.
(Category B3)
DBL Papaverine Hydrochloride Injection is not intended for use by women.
In animal studies, a single 140 mg/kg subcutaneous dose of papaverine hydrochloride to mice on gestation day 9 (timed to coincide with neural tube closure) caused increased fetal mortality and retardation, spinal cord kinking and dilation of the fourth brain ventricle. Neither neural anomaly was observed in control fetuses. Neural tube defects were also observed in explanted mouse and chick embryos exposed to 50-75 microgram/mL papaverine hydrochloride during neurulation in vitro. The relevance of these animal findings to humans is currently unknown.
There are no formal studies of papaverine hydrochloride in pregnant women.
 DBL Papaverine Hydrochloride Injection is not intended for use by women. It is not known whether papaverine hydrochloride is excreted in breast milk. Because many drugs are excreted in breast milk, caution should be exercised when papaverine hydrochloride is administered to a nursing woman.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Intracavernosal injection of papaverine hydrochloride may cause mild discomfort in the penis during injection, ecchymosis at the injection site, urethral bleeding, paraesthesia of the glans, difficulty in reaching orgasm and ejaculation, and 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.
Following is a listing of local and systemic adverse effects from clinical studies and case reports in which papaverine hydrochloride was used.

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.

Systemic adverse events.

Liver function abnormalities.
Symptoms/ signs resulting from vasodilation including headache, flushing, a sensation of heat in the pelvis, dizziness, photopsia, tachycardia, hypotension and syncope.
Vasovagal reactions.
Cardiac events.
Allergic reactions, urticaria.
Impaired ejaculation.
Death (one report).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

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 hydrochloride 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.
Overdose of papaverine hydrochloride via the intracavernosal route is likely to result in priapism. Patients should be instructed to seek urgent medical attention if an erection lasts for more than four hours.
Patients should be instructed to seek medical help immediately if they have self administered an overdose of papaverine hydrochloride.

Treatment.

In managing overdosage, a physician must consider the possibility of multiple drug overdoses, interaction among drugs and unusual drug kinetics.
The patient's airway must be protected, and ventilation and perfusion supported. Vital signs, blood gases, blood chemistry values and other variables need to be monitored.
In the event of convulsions, administration of diazepam or phenytoin needs to be considered. If seizures are refractory, general anesthesia with thiopentone or halothane and paralysis with a neuromuscular blocking agent may be necessary.
For hypotension, intravenous fluids, elevation of legs and administration of an inotropic vasopressor, such as dopamine, need to be considered. Theoretically, calcium gluconate may be helpful in treating some of the toxic cardiovascular effects of papaverine hydrochloride; the ECG and plasma calcium concentrations need to be monitored.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The principal therapeutic action of papaverine hydrochloride is its relaxant effect on smooth muscles, which leads to penile erection. It may induce erections by arteriolar relaxation, increased blood flow and volume due to relaxation of the sinusoidal wall of the corpora cavernosa and subsequent compression of venous channels between the sinusoids and the tunica albuginea.
The spasmolytic effect of papaverine hydrochloride is most pronounced on the vascular system, including coronary, cerebral, pulmonary and peripheral vasodilation; it also relaxes the bronchial, gastrointestinal, biliary and urinary tract smooth muscles. Papaverine hydrochloride has also been reported to have direct cardiac inotropic effects, leading to increased myocardial oxygen consumption, which can outstrip the effect of increased coronary blood flow if hypotension is also present. It can depress myocardial excitability, prolong the refractory period and depress myocardial conduction. In the presence of depressed conduction due to other causes (e.g. AV block), papaverine hydrochloride may produce transient ventricular arrhythmias. Papaverine hydrochloride can mildly stimulate respiration via action on the carotid and aortic body chemoreceptors.
Papaverine hydrochloride has minimal Central Nervous System (CNS) actions, although large doses may have a depressant effect in some patients. The drug also exhibits weak calcium channel blocking activity at high doses. Papaverine hydrochloride has been reported to have antiviral activity against respiratory syncytial virus, cytomegalovirus, measles and HIV. It may inhibit mitochondrial oxidative reactions, which can lead to severe lactic acidosis following large doses, especially overdose.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

The extent and time course of papaverine hydrochloride absorption have not been documented. In theory, systemic absorption following intracavernosal injection would initially be rapid, until the local effect of papaverine hydrochloride 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.

Distribution.

Approximately 90% of the drug is bound to plasma proteins. After intracavernosal injection, the peak plasma concentration is several times lower than after extracavernosal injection.

Metabolism.

Papaverine hydrochloride has a relatively short plasma half-life (1-2 hours) and is rapidly metabolised by the liver and excreted in the urine, chiefly as the glucuronide conjugates of phenolic metabolites.

Excretion.

The drug is excreted in the urine in an inactive form.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No long-term animal studies on the carcinogenic potential of papaverine hydrochloride have been performed.
In an Ames test, papaverine hydrochloride was weakly mutagenic to the TA100 but not the TA98 strain of Salmonella typhimurium, only in the presence of metabolic activation.

6 Pharmaceutical Particulars

6.1 List of Excipients

Water for injections.

6.2 Incompatibilities

A precipitate results when DBL Papaverine Hydrochloride Injection is added to lactated Ringer's Injection.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C. Protect from light.

6.5 Nature and Contents of Container

DBL Papaverine Hydrochloride Injection is supplied in clear glass ampoules in the following presentation and pack size:

DBL Papaverine Hydrochloride Injection 120 mg/10 mL.

5 x 10 mL ampoules.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.


The chemical name for papaverine hydrochloride is 6,7-dimethoxy-1-veratrylisoquinoline hydrochloride. The molecular weight of papaverine hydrochloride (C20H21NO4,HCl) is 375.9.
Papaverine hydrochloride is the hydrochloride of an alkaloid obtained from opium or prepared synthetically. It belongs to the benzylisoquinoline group of alkaloids. The chemical name for papaverine hydrochloride is 6,7-dimethoxy-1-veratrylisoquinoline hydrochloride.
The pH of the injection ranges between 3.0 and 5.0.

CAS number.

61-25-6.

7 Medicine Schedule (Poisons Standard)

Schedule 4 (Prescription Only Medicine).

Summary Table of Changes