Active ingredients: Alprostadil
Vitaros 2 mg / g cream
Vitaros 3 mg / g cream
Indications Why is Vitaros used? What is it for?
Vitaros is available in two strengths of 200 and 300 micrograms of alprostadil in 100 mg of cream.
Vitaros is used to treat erectile dysfunction (ED) in men aged 18 and over.
ED is the inability to achieve or maintain an erection sufficient to allow for satisfactory sexual intercourse.It can be caused by various factors, such as the medicines you take to treat other conditions, poor blood circulation in the penis, nerve damage, emotional problems, excess smoking or alcohol, and hormonal problems. ED often has multiple causes. Treatments for ED include: switching to other medicines if you are taking a drug that causes ED; the prescription of medicines; medical devices that induce an erection; surgery to correct blood flow in the penis; penile implants and psychological counseling. After the application of Vitaros, an erection appears within 5-30 minutes.
Do not stop taking any medicines unless your doctor tells you to.
Contraindications When Vitaros should not be used
Do not use Vitaros
- if you have problems such as low blood pressure when going from lying / sitting to standing, a history of heart attack and syncope (dizziness)
- if you are allergic to alprostadil or any of the other ingredients of this medicine (listed in section 6)
- if you have a condition that could lead to a long-lasting erection or a condition such as sickle cell or sickle cell trait anemia, thrombocythaemia, polycythemia, multiple myeloma or leukemia - if you have an abnormally shaped penis
- if you have an inflammation or infection in the penis
- if you are prone to venous thrombosis
- if you have hyperviscosity syndrome which could result in a long-lasting erection
- if you have been told not to have sex for health reasons, such as heart problems or a recent stroke
- if your partner is pregnant, breastfeeding or of childbearing age unless you are using a condom.
Precautions for use What you need to know before taking Vitaros
Talk to your doctor or pharmacist before using Vitaros if you suffer or have ever suffered in the past from any of the following local effects which have been seen with the use of Vitaros:
- Prolonged erection lasting more than 4 hours (priapism)
- Symptomatic hypotension (dizziness)
- Hepatic insufficiency and / or renal insufficiency, dose reduction may be necessary due to metabolic disturbances
- Fainting
A condom should be used in the following situations:
- your partner is pregnant or breastfeeding - your partner is of childbearing age
- to prevent sexually transmitted diseases
- during oral sex and anal sex.
Only latex condoms have been studied, any risk of damage to condoms made of other materials cannot be excluded.
Interactions Which drugs or foods can change the effect of Vitaros
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
The use of Vitaros in conjunction with other treatments for erectile dysfunction has not been studied. Therefore, if you are taking other erectile dysfunction drugs, Vitaros should not be used in combination as side effects may occur including dizziness, fainting. and prolonged erections. Vitaros has not been tested in patients with penile implants or treated with smooth muscle relaxants such as papaverine or with drugs used to induce erections such as alpha blocking drugs (eg intracavernous phentolamine, thymoxamine). The risk of priapism (painful prolonged abnormal erection) increases when used in combination.
Although it has not been studied, it is possible that the effect of Vitaros may decrease when taken in combination with antihypertensive, decongestant and appetite suppressant medicines.
If you are taking anticoagulant drugs, do not take Vitaros, the risk of urethral bleeding and haematuria may increase.
In combination with medicines for hypertension, the use of Vitaros may increase the symptoms of dizziness and fainting, especially in the elderly.
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
There are no data from the use of Vitaros in pregnant women. Pregnant women should not be exposed to Vitaros.
The use of Vitaros while breastfeeding is not recommended.
It is not known if Vitaros has an effect on human male fertility.
Driving and using machines
Vitaros can cause dizziness or fainting. Do not drive or operate machinery within 1-2 hours of administration.
Children and adolescents
Vitaros is not suitable for children or men under the age of 18.
Dosage and method of use How to use Vitaros: Dosage
Always use this medicine exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist.
Vitaros is available in two strengths of 200 and 300 micrograms of alprostadil in 100 mg of cream. Vitaros must be used in the amount necessary to achieve an erection. Each AccuDose container of Vitaros is for single use only and must be properly disposed of after use.
For an erection: The starting dose must be recommended by a doctor. Do not change the dose yourself. Ask your doctor who will give you information on the correct technique for administration and dose adjustment.
Do not apply Vitaros more than 2-3 times a week and no more than once within 24 hours. The effect appears 5-30 minutes after administration. The duration of the effect is approximately 1 to 2 hours. However, the actual duration varies from patient to patient.
Apply Vitaros on the tip of the penis about 5-30 minutes before starting sexual intercourse following the instructions below:
- Wash your hands before applying Vitaros. Remove the AccuDose container from the sachet by tearing off the notched edge. Keep the sachet to discard the used container later. Remove the cap from the tip of the container.
- Grasp the tip of the penis with one hand and gently widen the opening of the penis. Note, if he is not circumcised, first move the foreskin and then widen the opening of the penis.
- Hold the cylinder of the AccuDose container between your fingers and place the tip of the container over the opening of the penis and slowly (more than 5-10 seconds), push down the plunger with your finger until all the cream is ejected from the container. Note: Do not insert the tip of the container into the opening of the penis.
- Hold the penis upright for about 30 seconds to allow the cream to penetrate. There may be some excess cream. The amount of excess cream will vary depending on the patient and it is not unusual for half the dose to remain on the edge of the opening. Do not use a second container to compensate for cream not introduced into the opening of the penis. Excess cream residue covering the opening can be gently smeared on the skin surrounding the application site with the tip of a finger.
- Remember that each dose of Vitaros is for a single administration. Put the cap back on the AccuDose container and place it in the open sachet, fold and dispose of according to local regulations.
- Vitaros can be irritating to the eyes. Wash your hands after applying Vitaros.
Overdose What to do if you have taken too much Vitaros
If you use more Vitaros than you should
No cases of overdose requiring treatment have been reported with Vitaros.
In the event of an overdose with Vitaros, hypotension, fainting, dizziness, persistent pain in the penis and possible priapism (rigid erection lasting over 4 hours) may occur. Priapism can cause permanent worsening of erectile function. Contact your doctor immediately if you experience any of these effects.
If you are unsure about the use of this medicine, contact your doctor or pharmacist.
Side Effects What are the side effects of Vitaros
Like all medicines, Vitaros can cause side effects, although not everybody gets them.
If you have had an erection for more than 4 hours, contact your doctor immediately.
Your doctor may reduce the dose of Vitaros and stop treatment.
Common side effects (may affect more than 1 in 10 patients):
He:
- mild to moderate local pain, burning or pain and redness of the penis,
- skin rash,
- genital itching,
- penile edema,
- inflammation of the glans penis (balantitis),
- tingling, throbbing, numbness, burning of the penis.
In his partner:
- mild vaginal burning or itching, vaginitis
This effect may be due to the drug or the act of vaginal penetration. Using a water-based lubricant can help make vaginal penetration easier.
Uncommon, but potentially serious side effects (may affect up to 1 in 100 patients):
He:
- light-headedness / dizziness
- prolonged erection for more than 4 hours
- fainting
- low blood pressure or rapid heartbeat
- pain at the application site or extremity
- urethral stricture
- increased sensitivity
- itchy penis
- genital rash
- scrotal pain
- genital fullness
- lack of sensitivity in the penis
- inflammation of the urinary tract
In his partner: vulvovaginal itching
* Increased sexual / physical activity in combination with Vitaros may increase the risk of heart attack or stroke in patients with prior risk factors and illnesses (see section 2).
If any of these effects become severe, including any not listed in this leaflet, talk to your doctor or pharmacist.
Duration of side effects
Most effects are short-lived and resolve within 1-2 hours.
Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system http://www.agenziafarmaco.gov.it/it/content/modalit%C3%A0-disegnalazione-delle-sospette-reazioni-avverse-ai-medicinali. By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
Keep this medicine out of the reach and sight of children.
Do not use Vitaros after the expiry date which is stated on the carton, sachet and AccuDose container label after EXP. The expiry date refers to the last day of that month.
Store in a refrigerator (2 ° C - 8 ° C). Do not freeze.
The sealed sachets can be stored outside the refrigerator by the patient, at a temperature below 25 ° C up to a maximum of 3 days before use. At the end of this period, the product must be discarded. Each container is for single use only. Once opened, use it immediately and discard any unused part.
Store in the original package to protect the medicine from light.
Do not throw any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. This will help protect the environment.
Other_information "> Other information
What Vitaros contains
The active ingredient is Alprostadil
Each single-dose container contains 200 micrograms of alprostadil in 100 mg of cream (2 mg / g).
Each single-dose container contains 300 micrograms of alprostadil in 100 mg of cream (3 mg / g).
Vitaros is available in cardboard boxes with four single-dose containers.
The excipients are; purified water; ethanol, anhydrous; ethyl laurate; hydroxypropyl guar gum; dodecyl-2- (N, N-dimethylamino) -propionate hydrochloride; potassium dihydrogen phosphate; sodium hydroxide, for pH regulation; phosphoric acid, for pH regulation.
Description of what Vitaros looks like and contents of the pack
Vitaros is a white to off-white cream supplied in a single-dose container, AccuDose.
The container consists of a plunger, a cylinder and a protective cap supplied in a protective bag.
The card sleeves are made from aluminum / laminate foil.
The parts of the container are composed of polypropylene and polyethylene.
Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.
01.0 NAME OF THE MEDICINAL PRODUCT -
VITAROS CREAM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION -
Each single-use container contains 200 mcg of alprostadil in 100 mg of cream (2 mg / g).
Each single-use container contains 300 mcg of alprostadil in 100 mg of cream (3 mg / g).
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM -
Cream
Vitaros is a white to off-white cream supplied in a single-dose container (AccuDose). AccuDose is a container consisting of a plunger, a barrel and a protective cap contained in a single protective pouch.
04.0 CLINICAL INFORMATION -
04.1 Therapeutic indications -
Treatment of erectile dysfunction in men aged ≥ 18 years. Erectile dysfunction is the inability to achieve or maintain an erection sufficient to allow for satisfactory sexual intercourse.
04.2 Posology and method of administration -
Vitaros is applied to the tip of the penis.
Vitaros is available in two strengths of 200 and 300 mcg of alprostadil in 100 mg of cream. Vitaros must be used in the amount necessary to achieve an erection. Each AccuDose container of Vitaros is for single use only and must be properly disposed of after use. The effect appears 5-30 minutes after administration. The duration of the effect is approximately 1- 2 hours. However, the actual duration varies from patient to patient. Each patient should be instructed by an experienced physician on the proper technique for administering Vitaros before proceeding with self-administration. The maximum frequency of administration is no more than 2-3 times in a week and only once in a week. a period of 24 hours.
The starting dose should be recommended by a doctor. A starting dose of 300 micrograms may be considered especially in patients with severe erectile dysfunction, co-morbidities or lack of response to PDE-5 inhibitors. Patients who cannot tolerate the 300 mcg dose due to local side effects may drop to the lower 200 mcg dose.
Patients should be instructed on the correct administration technique, on possible side effects (for example: dizziness, fainting) and the need to avoid using machines until the individual tolerance level of the drug is clear. A higher dropout rate was found in the 300 mcg group compared to the 200 mcg group, by 30% and 20% respectively.
Method of administration:
Apply Vitaros on the tip of the penis (meatus) about 5-30 minutes before starting intercourse by following the instructions below:
1) Wash your hands before applying Vitaros. Remove the AccuDose container from the pouch by tearing off the notched edge. Save the sachet to discard the used AccuDose container later. Remove the cap from the tip of the AccuDose container.
2) Grasp the tip of the penis with one hand and gently widen the opening of the penis. (Note, if he is not circumcised, first lower the foreskin and hold it in that position while subsequently widening the opening of the penis).
3) Hold the cylinder of the AccuDose container between your fingers and place the tip of the container over the opening of the penis and slowly (more than 5-10 seconds), push down the plunger with your finger until all the cream is it is ejected from the AccuDose container. Note: Do not insert the tip of the container into the opening of the penis.
4) Hold the penis upright for about 30 seconds to allow the cream to penetrate. There may be some excess cream. The amount of excess cream will vary depending on the patient and it is not unusual for half the dose to remain on the edge of the opening. Do not use a second AccuDose container to compensate for cream not introduced into the opening of the penis. Excess cream residue covering the opening can be gently smeared on the skin surrounding the meatus with the tip of a finger.
5) Remember that each dose of Vitaros is for a single administration. Put the cap back on the AccuDose container and return it to the opened sachet, fold and dispose of in accordance with local regulations.
6) Vitaros can be irritating to the eyes. Wash your hands after applying Vitaros.
04.3 Contraindications -
Vitaros must not be used in patients with:
• Previous diseases such as orthostatic hypotension, myocardial infarction and syncope.
• Known hypersensitivity to alprostadil or to any of the other ingredients of Vitaros.
• Conditions that may predispose to priapism, such as sickle cell or sickle cell trait anemia, thrombocythemia, polycythemia or multiple myeloma, or leukemia.
• Abnormal penile anatomy, such as severe hypospadias, in patients with anatomical deformations of the penis, such as abnormal curvature, and in patients with urethritis and balanitis (inflammation / infection of the glans penis).
• Prone to venous thrombosis or who have hyperviscosity syndrome and therefore are at increased risk of priapism (rigid erection lasting 4 hours or more).
• Vitaros should not be used in patients for whom sexual activity is not recommended such as in men with unstable cardiovascular or cerebrovascular conditions.
• Vitaros should not be used for sexual intercourse with a woman of childbearing age unless the couple is using a condom.
04.4 Special warnings and appropriate precautions for use -
Local effects:
Prolonged erections lasting> 4 hours (priapism), although rare, were observed with the use of Vitaros. Priapism was observed in two 3-month studies in 1 patient (0.06%) and in study> 6 months in 5 (0.4%) patients, including 4 (0.3%) in the 200 mcg group and 1 (0.1%) in the 300 mcg group. In case of priapism, the patient should be informed of Seek immediate medical attention If priapism is not treated immediately, it can cause damage to penile tissue and permanent loss of potency.
Symptomatic hypotension (dizziness) and syncope occurred in a small percentage of patients (2/459 (0.4%), 6/1591 (0.4%), and 6/1280 (0.5%) at doses of alprostadil of 100, 200 and 300 micrograms, respectively, during the Phase 3 studies. Patients should be advised to avoid activities, such as driving or performing hazardous activities, which could lead to accidents if syncope develops following the administration of Vitaros.
Before starting treatment with Vitaros, the causes of erectile dysfunction, which are treatable, must be ruled out by appropriate diagnostic methods.
Furthermore, patients with previous medical conditions, such as orthostatic hypotension, myocardial infarction and syncope, should not use Vitaros (see CONTRAINDICATIONS, section 4.3).
No clinical studies have been conducted in patients with a history of neurological disease or spinal injury.
The pharmacokinetics of Vitaros have not been evaluated in patients with hepatic and / or renal insufficiency. Dosage may need to be reduced in these populations due to metabolic disturbances.
General Precautions:
Vitaros must be applied following the instructions above. Involuntary intraurethral exposure may cause penile burning or tingling and painful sensations. The effect of long-term repeated intraurethral exposure of Vitaros is unknown.
Patients should be advised that Vitaros offers no protection against the spread of sexually transmitted diseases. Patients and partners using Vitaros should be advised on the necessary protective measures to avoid the spread of sexually transmitted agents, including human immunodeficiency virus (HIV).
Healthcare professionals should encourage their patients to inform their sexual partners that they are using Vitaros. The partners of those using Vitaros may experience adverse events, most commonly vaginal irritation. The use of a condom is therefore recommended.
The effects of Vitaros on the oral or anal mucosa have not been studied. A condom should be used for oral sex (fellatio) or anal sex.
Vitaros has no contraceptive properties. It is recommended that couples using Vitaros use adequate contraception if the partner is of childbearing age.
There is no information on the early pregnancy effects of alprostadil in relation to the amounts received by female partners. A condom should be used in case of sexual intercourse with women of childbearing age, pregnant or breastfeeding women.
The use of the drug has been studied only in conjunction with latex-based condoms, any risk of damage to condoms made of other materials cannot be excluded.
04.5 Interactions with other medicinal products and other forms of interaction -
No pharmacokinetic or pharmacodynamic interaction studies have been conducted with Vitaros. Based on drug metabolism (see "Pharmacokinetic Properties"), drug-drug interactions are considered unlikely.
Interaction effects
The safety and efficacy of Vitaros has not been studied in conjunction with other treatments for erectile dysfunction, particularly with phosphodiesterase-5 (PDE-5) inhibitors or sildenafil, tadalafil and vardenafil. Therefore, Vitaros should not be used. in combination with PDE5 inhibitors Since both Vitaros and PDE5 inhibitors have cardiovascular effects, a further increase in cardiovascular risk cannot be excluded.
No interaction studies have been performed relating to the use of Vitaros in patients with penile implants or treated with smooth muscle relaxants such as papaverine and drugs used to induce erection such as alpha blocking drugs (eg intracavernous phentolamine, thymoxamine). There is a risk of priapism (painful prolonged abnormal erection) if Vitaros is used concomitantly with these drugs.
No interaction studies have been performed between Vitaros and sympathomimetics, decongestants and appetite suppressants. When used in combination with these medicines, Vitaros may have a reduced effect (inhibition of the pharmacological effect).
No interaction studies have been performed between Vitaros and anticoagulant drugs or platelet aggregation inhibitors. The use of Vitaros in combination with these drugs could increase the risk of urethral bleeding and haematuria.
The combination with antihypertensive drugs and vasoactive drugs could increase the risk of hypotension, especially in the elderly.
04.6 Pregnancy and breastfeeding -
Pregnancy
There are no data on the use of Vitaros in pregnant women. Indirect exposure to alprostadil in women is likely to be low.
Animal data after exposure to high doses of alprostadil show toxic effects on reproduction (see section 5.3).
Pregnant women should not be exposed to Vitaros.
Feeding time
It is unknown whether indirect exposure to alprostadil leads to significant excretion into breast milk. The use of Vitaros while breastfeeding is not recommended.
Fertility
In male rabbits, atrophy of the seminiferous tubules of the testes was observed after repeated administration. It is not known if Vitaros has an effect on human male fertility.
04.7 Effects on ability to drive and use machines -
No studies on the effects on the ability to drive and use machines have been performed.
As dizziness and syncope (fainting) have been reported rarely during clinical trials with Vitaros, patients should avoid tasks, such as driving or risky activities, for at least 1-2 hours after administration of Vitaros, as the onset of syncope could cause accidents.
04.8 Undesirable effects -
Table of adverse reactions
The most frequently reported adverse events in treatment with Vitaros are listed in the table below (very common ≥ 1/10; common ≥ 1/100,
Table 1 Adverse Reactions
Special populations
* There is no clear indication that alprostadil causes an increased risk of cardiovascular events, other than vasodilatory effects. However, it cannot be excluded that patients with prior disease or risk factors have an increased risk of having events, concomitant with an increase in sexual / physical activity that is associated with the use of alprostadil (see sections 4.3 and 4.4).
Reporting of suspected adverse reactions
Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via http: // www. Agenziafarmaco.gov.it/it/content/modalit%C3%A0-di-segnalazione-delle-sospette-reazioni-avverse-ai-medicinali.
04.9 Overdose -
No cases of overdose requiring treatment have been reported with Vitaros.
In the event of an overdose with Vitaros, hypotension, syncope, dizziness, penile pain and possible priapism (rigid erection lasting for more than 4 hours) could occur. Priapism can cause permanent worsening of erectile function. Patients with suspected overdose who experience these symptoms should be kept under close medical surveillance until local or systemic symptoms are resolved.
The patient should be advised to consult a physician immediately if an erection persists for more than 4 hours. The following measures should be taken:
• Have the patient lie on his back or on his side. Apply ice alternately for two minutes on each upper inner side of the thigh (this should lead to reflex relaxation of the venous valves). If there is no response within 10 minutes, discontinue treatment.
• If this treatment is ineffective and the erection lasts for more than 6 hours, penile aspiration should be performed. Using sterile procedures, insert a 19-21 gauge butterfly needle into the corpus cavernosum and aspirate 20-50 mL of blood. This should lead to detumescence of the penis. If necessary, repeat the operation on the opposite side of the penis.
• If treatment is unsuccessful, administration of an a-adrenergic drug by intercavernous injection is recommended. This operation should be done with caution, although in the treatment of priapism the usual contraindication to the intrapenic administration of a vasoconstrictor is not valid. Blood pressure and heart rate should be continuously monitored during the procedure. Extreme caution should be used in patients who they have coronary artery disease, uncontrolled hypertension, cerebral ischemia, and in all subjects who are being treated with MAO inhibitors (mono amino oxidase). In the latter case, aids for the control of hypertensive crises must be available.
• A 200 mcg / ml solution of phenylephrine should be prepared and 0.5 to 1.0 ml of solution injected every 5-10 minutes. Alternatively, a 20 mcg / ml solution of adrenaline can be used. If necessary, this can be followed by further aspiration of blood through the same butterfly needle. The maximum dose of phenylephrine should be 1 mg, that of adrenaline 100 mcg (5 ml of solution).
• Metaraminol can be used as an alternative, but it should be borne in mind that fatal hypertensive crises have been reported following administration of this drug. If even this treatment proves ineffective in resolving priapism, the patient should undergo surgery immediately.
05.0 PHARMACOLOGICAL PROPERTIES -
05.1 "Pharmacodynamic properties -
Pharmacotherapeutic group: Drugs used in erectile dysfunction
ATC code: G04BE01
Mechanism of action:
Alprostadil is chemically identical to Prostaglandin E1, whose action involves dilation of blood vessels in the erectile tissues of the corpora cavernosa and increased cavernous arterial flow, causing penile stiffness.
After the application of Vitaros, an erection occurs within 5-30 minutes. Alprostadil has a short half-life in men and the effect on erection can last from 1 to 2 hours after administration.
Efficacy: Two Phase 3 studies evaluated the efficacy of Vitaros in patients with erectile dysfunction. Compared to placebo, statistically significant improvement was observed in the alprostadil 100, 200 and 300 mcg groups for each of the primary efficacy endpoints. namely, the International Index of Erectile Function (IIEF) erectile function (EF) domain score and improved vaginal penetration and ejaculation. In addition, overall improvements and statistical significance of the treatment groups were also reported compared to the placebo in several of the secondary efficacy variables, including other IIEF domain scores (orgasmic function, sexual satisfaction, and overall satisfaction), Patient Self-Assessment of Erection (PSAE), and Global Assessment Questionnaire (GAQ).
Subpopulation efficacy: Similar improvements in IIEF EF scores to those of all patients were seen in various patient subgroups (diabetic, cardiac, prostatectomy, hypertension, and patients who did not respond to prior Viagra therapy and in the two age groups (≤ 65 and> 65 years) in the IIEF satisfaction scales (International Index of Erectile Function) EF.
05.2 "Pharmacokinetic properties -
Absorption: Absolute topical bioavailability has not been determined. In a pharmacokinetic study, patients with erectile dysfunction were treated with 100 mg of Vitaros cream at doses of 100, 200 and 300 mcg of alprostadil. Plasma levels of PGE1, and its metabolite, PGE0 were low or undetectable in most subjects and in most sampling times and pharmacokinetic parameters could therefore not be estimated. Cmax values and AUC values of 15-keto-PGE0 were low and showed a minor increase over dose proportional increase in the therapeutic range of 100-300 μg. Maximum plasma concentrations of 15-keto-PGE0 were achieved within one hour of administration.
Table 2
Mean (SD) Pharmacokinetic parameters for 15-keto-PGE0
Distribution: After administration to the meatus and glans penis, alprostadil is rapidly absorbed into the corpus spongiosum and corpora cavernosa via collateral vessels. The remainder enters the pelvic venous circulation through the veins that drain the corpus spongiosum.
Metabolism: Following topical administration, PGE1 is rapidly metabolised locally by enzymatic oxidation of the 15-hydroxyl group to 15-keto-PGE1. 15-keto-PGE1 retains only 1-2% of the biological activity of PGE1 and rapidly declines to form the more abundant inactive metabolite, 13,14-dihydro, 15-keto-PGE which is primarily eliminated by the kidneys and liver.
Excretion: Following intravenous administration of tritium-labeled alprostadil in humans, the labeled drug disappears rapidly from the blood within the first 10 minutes and only a low level of radioactivity remains in the blood after 1 hour. The metabolites of alprostadil are excreted primarily via the kidney. approximately 90% of the administered intravenous dose is excreted in the urine within 24 hours after administration.The remainder is excreted in the faeces There is no evidence of tissue retention of alprostadil or its metabolites following intravenous administration.
Pharmacokinetics in special populations:
Lung disease: Patients with lung disease may have a reduced ability to eliminate the drug. In patients with adult respiratory distress syndrome, intravenous PGE1 pulmonary extraction was reduced by approximately 15% compared to a control group of patients with normal respiratory function.
Gender: The effects of sex on the pharmacokinetics of Vitaros have not been studied and pharmacokinetic studies in female partners have not been conducted.
Elderly, children: The effects of age on the pharmacokinetics of topical alprostadil have not been studied.Vitaros is not intended for use in children or anyone under the age of 18.
05.3 Preclinical safety data -
Alprostadil, the excipient DDAIP and Vitaros (including DDAIP) did not show genotoxic potential.
Carcinogenicity studies have not been conducted with alprostadil or Vitaros. Carcinogenicity evaluations of the excipient DDAIP did not reveal tumor formation after topical administration in mice and subcutaneously in rats. In the transgenic mouse Tg.AC, DDAIP at a concentration of 1.0% and 2.5% induced the development of papillomas in both females and males This effect is probably not relevant to humans, and is probably caused by irritation.
Alprostadil has no effect on sperm count or morphology. However, the excipient DDAIP caused atrophy of the seminiferous tubules of the testes in rabbits after local administration at a concentration of 5%. A direct spermatotoxic effect of DDAIP has not been tested, therefore the relevance of a possible reduction in male fertility in the humans Subcutaneous administration of DDAIP to rats had no effect on fertility.
Low dose bolus administration of Alprostadil subcutaneously in pregnant rats showed an embryotoxic effect (decreased fetal weight). Higher doses resulted in increased resorptions, a reduced number of live fetuses, increased incidence of visceral and skeletal changes and malformations and maternal toxicity. Intravaginal administration of PGE1 in pregnant rabbits did not result in any harm to the fetus.
Reproductive toxicity studies with DDAIP, in rats and rabbits after subcutaneous administration, did not show effects in rats while in rabbits, at high doses, fetotoxicity and increased malformations probably related to maternal toxicity were observed. No effects on postnatal development were evident in the rat.
06.0 PHARMACEUTICAL INFORMATION -
06.1 Excipients -
Purified water, Ethanol, anhydrous, Ethyl laurate, Hydroxypropyl guar gum, Dodecyl-2- (N, N- dimethylamino) -propionate hydrochloride, Potassium dihydrogen phosphate, Sodium hydroxide, for pH adjustment, Phosphoric acid, for pH regulation
06.2 Incompatibility "-
Not applicable
06.3 Period of validity "-
9 months for Vitaros 2 mg / g cream
18 months for Vitaros 3 mg / g cream
Once opened, use immediately, discard any unused part.
06.4 Special precautions for storage -
Store in a refrigerator (2 ° C - 8 ° C).
Do not freeze.
The sealed pouches can be stored out of the refrigerator by the patient, at a temperature below 25 ° C for up to 3 days before use.
At the end of this period, the product must be discarded.
Store in the original package to protect the medicine from light.
06.5 Nature of the immediate packaging and contents of the package -
Vitaros is supplied in single sachets containing an AccuDose container. Each single container contains 100 mg of cream. Vitaros is available in a carton containing four containers. The sachets consist of an aluminum / laminate layer. The container is made up of polypropylene and polyethylene.
06.6 Instructions for use and handling -
Each container is for single use only.
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 HOLDER OF THE "MARKETING AUTHORIZATION" -
Bracco s.p.a.
Via E. Folli, 50 - 20134 Milan
08.0 MARKETING AUTHORIZATION NUMBER -
"2 mg / g cream" 4 single-dose containers in PP / PE of 100 mg in single sachet AIC 041332014 "3 mg / g cream" 4 single-dose containers in PP / PE of 100 mg in single sachet AIC 041332026
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION -
31.05.2013
10.0 DATE OF REVISION OF THE TEXT -
October 2013
