- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
PosologyThe drug solution should be prepared shortly before the injection.
Dosage for diagnosis of erectile dysfunctionInjections for diagnostic evaluation and dose titration must be performed by the treating physician. He will determine an individual dose suitable to produce an erectile response for diagnostic purposes.For erectile dysfunction of neurological origin, the starting dose is 1.25 mcg Viridal Duo. In all other patients with erectile dysfunction the recommended starting dose is 2.5 mcg. Dose adjustments may be performed in increments of about 2.5 mcg to 5 mcg Viridal Duo. Most of the patients require between 10 and 20 mcg per injection. Some patients may need to be titrated to higher doses. Doses exceeding 20 mcg should be prescribed with particular care in patients with cardiovascular risk factors. The dose per injection should never exceed 40 mcg. Dosage for treatment of erectile dysfunction Treatment initiation and dose titration Injections for treatment initiation and dose titration must be performed by the treating physician. The recommended starting dose is 1.25 mcg Viridal Duo in patients with erectile dysfunction of primary neurological origin. In all other patients with erectile dysfunction 2.5 mcg is the recommended starting dose. Dose adjustments may be performed in increments of about 2.5 mcg to 5 mcg. Most patients require between 10 and 20 mcg per injection. Some patients may need to be titrated to higher doses. The dose per injection should never exceed 40 mcg. Dosage for self-injection therapyBefore starting treatment at home, each patient or the patient's partner has to be taught by a physician how to prepare the drug and perform the injection. In no cases should the injection therapy be started without precise instructions by the physician. The patient should only use his optimum individual dosage which has been pre-determined by his physician using the above-mentioned procedure. This dose should allow the patient to have an erection at home, which should not last longer than one hour. If he experiences prolonged erections beyond 2 hours but less than 4 hours, the patient is recommended to contact his physician to re-establish the dose of the drug. The maximum injection frequency recommended is 3 times a week with an interval of at least 24 hours between the injections.
Follow-upAfter the first injections and at regular intervals, e.g. every three months, the physician should re-evaluate the patient. Any local adverse reaction, e.g. haematoma, fibrosis or nodules should be noted and controlled. Following discussion with the patient, an adjustment of dosage may be necessary.
Method of preparation and administrationPrior to injection the needle should be screwed onto the tip of the injector. After disinfecting the tip of the cartridge with one of the alcohol swabs, the cartridge should then be inserted into the injector. The tip should face towards the front of the applicator.Put the cartridge into the Easy Duo device. Screw the syringe and plunger together. Hold the device in the vertical position and push the plunger upwards. The solvent will by-pass the upper stopper into the front chamber and dissolve the dry substance within a few seconds.As soon as the dry substance is reconstituted, the larger external and the smaller inner protective cap have to be removed from the needle. The device is still held in the vertical position and the air should then be expelled out of the cartridge by tapping against the cartridge and by carefully pushing the plunger until the air is pressed out. The plunger is pushed up until the grey stopper reaches the prescribed dose. Viridal Duo is injected into either the right or the left cavernous body of the penile shaft. Once the needle is in the cavernous body, the injection should be done within 5 to 10 seconds and is very easy without much resistance if the needle is in the correct position.The development of an erection will start approximately 5 15 minutes after the injection.
NotesInjections for treatment initiation, diagnostic evaluation and dose titration must be performed by the treating physician. For patients who require a starting dose of 1.25 mcg, the dose of the reconstituted injection solution can be extracted from the carpoule using a syringe with a needle size 29 G x1/2 (0.33 mm x 12.7 mm) and appropriately graduated to extract and administer 0.125 ml injection volume from the carpoule containing 10 mcg Viridal Duo. Under aseptic conditions the solution can be extracted from the carpoule through the rubber seal. Unused injection solution must be discarded.Unused solution must be discarded immediately.
|System Organ Class||Frequency||Undesirable effects|
|Infections and Infestations||Uncommon||Fungal infection, common cold|
|Blood and lymphatic system disorders||Very rare||Isolated cases of thrombocytopenia|
|Immune System Disorders||Rare||Hypersensitivity ranging from dermatitis allergic urticaria to anaphylactic / anaphylactoid reaction|
|Nervous System Disorders||Uncommon||Headache, hypoaesthesia , hyperaesthesia, presyncope|
|Not known||Amnesia, cerebro-vascular accident|
|Cardiac Disorders||Uncommon||Supraventricular extrasystoles|
|Rare||Circulatory effects such as short periods of hypotension|
|Not known||Myocardial ischemia, myocardial infarction|
|Uncommon||Vein disorder, hypotension, vasodilation, peripheral vascular disorder|
|Gastrointestinal Disorders||Uncommon||Nausea, dry mouth|
|Skin and Subcutaneous Tissue Disorders||Uncommon||Rash, pruritis, scrotal erythema, erythema, hyperhidrosis|
|Muskuloskeletal and Connective Tissue Disorders||Common||Muscle spasms|
|Renal and Urinary Disorders||Uncommon||Dysuria, haematuria, pollakiuria, micturition urgency, urethral heamorrhage|
|Reproductive System and Breast Disorders||Very common||Penile pain|
|Common||Erection increased, Peyronie's disease, penis disorder, fibrotic alterations (e.g. fibrotic nodules, plaques at the site of injection or in the corpus cavernosum) can occur during long term treatment|
|Uncommon||Fibrotic alterations associated with slight penile axis deviations, erectile dysfunction, balanitis, priapism (mainly seen during dose titration), phimosis, painful erection, ejaculation disorder, testicular pain, scrotal disorder, scrotal erythema, scrotal pain, pelvic pain, testicular swelling, testicular oedema, scrotal oedema, spermatocele, testicular disorder, testicular mass|
|Rare||Fibrotic changes of the cavernous body during a long term treatment lasting up to 4 years.|
|General Disorders and Administrative Site Conditions||Common||Haematoma, ecchymosis, injection site haematoma, burning sensation during injection and after the injection, pain of mostly mild intensity at the site of injection.|
|Uncommon||Spot-like haemorrhage / spot-like bruises at the site of puncture, haemosiderin deposits, inflammation, oedema peripheral, oedema, injection site haemorrhage, injection site mass, injection site inflammation, injection site pruritis, injection site swelling and reddening, injection site oedema, injection site irritation, injection site anaesthesia, injections site pain, injection site warmth, asthenia, haemorrhage|
|Not known||Penile oedema|
|Investigations||Uncommon||Blood pressure decreased, heart rate increased, blood creatinine increased|
Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation 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 via the national reporting system listed below.The Yellow Card SchemeWebsite: www.mhra.gov.uk/yellowcardBy reporting side effects, you can help provide more information on the safety of this medicine.
SymptomsFull rigid erections lasting more than four hours.Overdosage was not observed in clinical trials with alprostadil.
TreatmentIf intracavernous overdose of Viridal Duo occurs, the patient should be placed under medical supervision until any systemic effects have resolved and/or until penile detumescence has occurred. • Observation of the erection, since spontaneous detumescence is frequent but the treatment of priapism (prolonged erection) should not be delayed more than six hours.• Symptomatic treatment of any systemic symptoms would be appropriate.• Initial therapy should be by penile aspiration. Using aseptic technique, insert a 19-21 gauge butterfly needle into the corpus cavernosum and aspirate 20-50 ml of blood. This may detumesce the penis. If necessary, the procedure may be repeated on the opposite side of the penis until a total of up to 100 ml blood has been aspirated.• If still unsuccessful, intracavernous injection of alpha-adrenergic medication is recommended. Although the usual contraindication to intrapenile administration of a vasoconstrictor does not apply in the treatment of priapism, caution is advised when this option is exercised. Blood pressure and pulse should be continuously monitored during the procedure. Extreme caution is required in patients with coronary heart disease, uncontrolled hypertension, cerebral ischaemia, and in subjects taking monoamine oxidase inhibitors. In the latter case, facilities should be available to manage a hypertensive crisis. A 200 microgram/ml solution of phenylephrine should be prepared, and 0.5 to 1.0 ml of the solution injected every 5 to 10 minutes. Alternatively, a 20 microgram/ml solution of epinephrine should be used. • If necessary, this may be followed by further aspiration of blood through the same butterfly needle. The maximum dose of phenylephrine should be 1 mg, or epinephrine 100 micrograms (5 ml of the solution). As an alternative metaraminol may be used, but it should be noted that fatal hypertensive crises have been reported. If this still fails to resolve the priapism, urgent surgical referral for further management, which may include a shunt procedure, is required.
Pharmacotherapeutic groupATC Code: Other urologicals G04BX 05
Mechanism of actionAlprostadil [Prostaglandin E1 (PGE1)], the active ingredient of Viridal Duo, is an endogenous compound derived from the essential fatty acid dihomogammalinolenic acid. Alprostadil is a potent smooth muscle relaxant that produces vasodilation and occurs in high concentrations in the human seminal fluid. Pre-contracted isolated preparations of the human corpus cavernosum, corpus spongiosum and cavernous artery were relaxed by alprostadil, while other prostanoids were less effective. Alprostadil has been shown to bind to specific receptors in the cavernous tissue of human and non-human primates.The binding of alprostadil to its receptors is accompanied by an increase in intracellular cAMP levels. Human cavernosal smooth muscle cells respond to alprostadil by releasing intracellular calcium. Since relaxation of smooth muscle is associated with a reduction of the cytoplasmic free calcium concentration, this effect may contribute to the relaxing activity of this prostanoid.
PharmacodynamicsIntracavernous injection of alprostadil in healthy monkeys resulted in penile elongation and tumescence without rigidity. The cavernous arterial blood flow was increased for a mean duration of 20 min. In contrast, intracavernous application of alprostadil to rabbits and dogs caused no erectile response.Systemic intravascular administration of alprostadil leads to a vasodilation and reduction of systemic peripheral vascular resistance. A decrease in blood pressure can be observed after administration of high doses. Alprostadil has also been shown in animal and in vitro tests to reduce platelet reactivity and neutrophil activation. Additional alprostadil activity has been reported: increase in fibrinolytic activity of fibroblasts, improvement of erythrocyte deformability and inhibition of erythrocyte aggregation; inhibition of the proliferative and mitotic activity of non-striated myocytes; inhibition of cholesterol synthesis and LDL-receptor activity; and an increase in the supply of oxygen and glucose to ischaemic tissue along with improved tissue utilisation of these substrates.
MetabolismEnzymatic oxidation of the C15-hydroxy group and reduction of the C13,14 double bond produce the primary metabolites, 15-keto-PGE1, PGE0 (13,14-dihydro-PGE1) and 15-keto-PGEo. Only PGE0 and 15-keto-PGEo have been detected in human plasma. Unlike the 15-keto metabolites, which are less pharmacologically active than the parent compound, PGE0 has a potency similar to that of PGE1 in most respects.In symptomatic volunteers, the mean endogenous PGE0 venous plasma concentrations measured before an intracavernous injection are approximately 1 pg/ml. After the injection of 20 mcg of alprostadil, the PGE0 plasma concentrations increase to concentrations of about 5 pg/ml within 20 minutes followed by a return to concentrations close to baseline. The terminal half-life of PGE0 is about 30 minutes.
ExcretionAfter further degradation of the primary metabolites by beta and omega oxidation, the resulting, more polar metabolites are excreted primarily with the urine (88%) and the faeces (12%) and there is no evidence of tissue retention of PGE1 or its metabolites.
AdviceThe content of the front chamber of the cartridge consists of a white, dry powder, which forms a compact layer, approximately 8 mm in height. The layer may show cracks and crumble slightly. In case of damage to the cartridge, the usually dry content of the front chamber becomes moist and sticky and extensively loses volume. Viridal Duo must not be used in this case. The bottom chamber contains the clear, colourless sodium chloride solvent solution. The dry substance dissolves immediately after addition of the sodium chloride solution. Initially after reconstitution the solution may appear slightly opaque due to the presence of bubbles. This is of no relevance and disappears within a short time to give a clear solution.Disposal of needle: disable needle then dispose of in a sharps container. Disposal of cartridge: no special requirements.
UCB Pharma Limited
208 Bath Road, Slough, Berkshire, SL1 3WE
+44 (0)1753 534 655
+44 (0) 1773 510123