INFORMATION FOR HEALTH PROFESSIONALS
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Dose per 0.35 ml contains 0.025 mg of aviptadil and 1 mg of phentolamine mesilate.
Dose per 0.35 ml contains 0.025 mg of aviptadil and 2 mg of phentolamine mesilate.
The Invicorp 1 and Invicorp 2 auto-injector delivers 0.35 ml of the product in a single dose, packed singly in pouches or ampoules containing 0.35 ml of product.
Phentolamine mesilate is a short-acting alpha-adrenoreceptor antagonist. It causes vasodilatation and a fall in blood pressure resulting from the blockade of both post-junctional vascular alpha 1 and alpha 2 adrenoreceptors with almost equal efficacy. It also has a direct effect on smooth muscle to cause relaxation which is independent of alpha blockade.
Following the discovery of nerves possessing aviptadil immunoreactivity in the male genital tract, a putative role for aviptadil in local nervous control of the smooth muscle activity in the male urogenitary tract was considered. The veno-occlusion resulting from the relaxation of smooth muscle appears to be under the control of aviptadil. In human corpus cavernous smooth muscle preparations, aviptadil has been found to act as a relaxant to both spontaneous activity and electrically pre-contracted tissue.
After administration of Invicorp it will usually take a few minutes for an erection to occur. Normally the erection will dutumesce after sexual intercourse and would not last for longer than an hour.
In a study on 12 healthy subjects, the mean maximum measured plasma aviptadil concentration was 396.6 pmoles/L and occurred in a mean time of 1.4 minutes. The mean area under the plasma aviptadil concentration time curve was 10.4 pmoles.hr/L. The mean terminal rate constant was 25.2042 hours-1 equivalent to a half life of 1.7 minutes.
The mean maximum measured plasma concentration of phentolamine mesilate was 79.5 ng/ml and occurred at a mean time of 1.3 minutes. The mean AUC extrapolated to the next no data point was 137.4 ng/ml. A terminal t½ of approximately 1.2 minutes was calculated from the available data. Total body clearance of phentolamine mesilate was determined to be 14.4 L/min, approximately 5 times the cardiac output.
The mean maximum measured plasma aviptadil concentration was 37.2 pmoles/L and occurred in a mean time of 4.3 minutes. The mean area under the curve was 6.1 pmoles.hr/L. the mean terminal rate constant was 7.8231 hours-1 equivalent to a half life of 5.3 minutes.
In a study on 21 patients, the mean maximum base line adjusted measured plasma aviptadil concentration was 16.3 pmoles/L and occurred in a mean time of 11.2 minutes. The mean area under the curve was 4.3 pmoles hr/L, and the half life 8.5 minutes.
The mean maximum plasma phentolamine mesilate concentration was 12.8 ng/ml occurring at a mean time of 12 minutes. The mean area under the curve was 6.3 ng.hr/ml and the half life 101 minutes.
Invicorp is used in the treatment of male erectile dysfunction, weak erection and impotence, and as a diagnostic test in the diagnosis of erectile dysfunction.
Invicorp is administered by direct intracavernosal injection and is not effected by food intake.
The first injection of Invicorp should be made under medical supervision and used as directed by a physician.
The initial dose is one injection of Invicorp 1, which may be increased to one injection of Invicorp 2, depending upon therapeutic response.
The frequency of injection should be no more than once daily and no more than three times weekly for either Invicorp 1 or Invicorp 2.
The product should be allowed to warm up to room temperature before use.
Intracavernous Invicorp should not be administered to patients who have a known hypersensitivity to either aviptadil or phentolamine mesilate or any of the other constituents.
Invicorp should not be used in men for whom sexual activity is inadvisable or contraindicated such as patients in the first 6 weeks of recovery following a myocardial infarction or life threatening arrhythmia.
The product should not be administered to patients who have conditions, which might predispose them to priapism such as sickle cell anaemia, multiple myeloma or leukaemia.
This product should also not be used if the patient has a penile implant.
Very occasionally a prolonged erection and/or priapism may occur. Patients should report any painful or uncomfortable erection (that lasts for more than 4 hours) to a physician.
Painful erection is more likely to occur in patients with anatomical deformations of the penis such as angulation, phimosis, cavernosal fibrosis, Peyronie's disease or plaques.
Mild transient flushing of the face or trunk occurs commonly. Rarely this is associated with discomfort and palpitations or tachycardia, in which case patients may be withdrawn from treatment.
Patients who are taking anticoagulants (such as heparin or warfarin) concomitantly to Invicorp therapy may be liable to increased bleeding following an intracavernosal injection.
Correct injection technique is important; patients should not be prescribed Invicorp without adequate training.
Fibrosis has been rarely reported with the prolonged use of other intracavernosal pharmacotherapies. Whilst not so far observed on Invicorp, the possibility of an association must be considered.
Acute toxicity testing has shown that the highest non-lethal I.V. dose of Invicorp in rats as 1.25 µg/kg aviptadil: 50 mg/kg phentolamine mesilate bodyweight.
No evidence of mutagenic potential has been detected following a battery of tests on Invicorp.
Animal reproduction studies have not been performed with the combination of aviptadil and phentolamine mesilate.
Invicorp is presumed to be safe or unlikely to produce an effect on the ability to drive or use machinery.
Flushing is a commonly observed event following successful administration with Invicorp. This is seldom troublesome and can be difficult to distinguish from the flushing associated with sexual intercourse. More rarely tachycardia has also been reported.
Very rarely patients may find their erections are uncomfortable or painful following use of Invicorp. Occasionally bruising of the penis at the site of injection may occur which will be less problematical once patients become more experienced in the techniques of self-administration.
Haematoma has occasionally been reported at the site of injection.
Invicorp is not intended for use concomitantly with other therapies for erectile dysfunction. Certain anti-hypertensive drugs such as alpha-adrenergic receptor blockers can exacerbate the symptoms of erective dysfunction. In the experience of use of Invicorp with anti-hypertensives or other cardiovascular drugs no clinical interaction had been observed. The potential hazards associated with sexual intercourse in patients on multiple pharmacotherapy for cardiovascular disease may be increased by the treatment themselves and by the patients underlying cardiac disease. Invicorp is not known to be incompatible with any medicines.
Prolonged erection and/or priapism are known to occur with vasoactive substances following intracavernous injection.
The treatment of prolonged erection (priapism) should not be delayed more than 6 hours. 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 dutumesce the penis. If necessary this may be repeated on the opposite side of the penis. If still unsuccessful, intracavernosal injection of alpha-adrenergic medication is recommended. Blood pressure and pulse should be continuously monitored during this 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 situation, facilities should be available to manage a hypertensive crisis. A 200 µg/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 µg/ml solution of adrenaline should be administered with further aspiration of blood. The maximum dose of phenylephrine should be 1 mg or adrenaline 100 µg (5 ml of solution). If this still fails to resolve the priapism, urgent surgical referral for further management, which may include a shunt procedure is required.
Long-term storage of Invicorp may be either in a freezer or refrigerator under the following conditions.
Autoinjectors
18 months at -20 °C
12 months stored at 2-8 °C.
Ampoules
22 months at -20 °C
15 months at 2-8 °C.
Whilst the product should normally be stored refrigerated, short periods of 2 or 3 days at room temperature (below 25 °C) will not be detrimental to the product.
Shipment of product may be undertaken at ambient temperature and returned to the refrigerator providing the overall delivery time does not exceed 48 hours. For longer periods the product may not be subsequently returned to cold storage.
Prescription medicine.
Can be supplied either as a single auto-injector or a single pack containing 1 ampoule, 1 syringe and 2 needles or a single pack containing two ampoules, 2 syringes and 4 needles.
Phentolamine mesilate C17H19N3O.CH3SO3H
= 377.5
Aviptadil C147H238N44O42S = 3326.2
Excipients (Qualitative)
Sodium chloride
Ethylenediamine disodium salt
Phosphoric acid
Sodium hydroxide
Hydrochloric acid
Water for Injection
Douglas Pharmaceuticals Ltd
P O Box 45-027
Auckland 1230
Ph: (09) 835-0660
Fax: (09) 835-0665
5th December 2003