Active ingredients: Dapoxetine
Priligy 30 mg film-coated tablets
Priligy 60 mg film-coated tablets
Indications Why is Priligy used? What is it for?
Priligy contains an active substance, called 'dapoxetine', which belongs to a group of medicines called 'selective serotonin reuptake inhibitors' (SSRIs). Priligy may also be known as a "urological" drug.
Priligy increases the time it takes to ejaculate and can improve control. This can reduce the frustration or worry caused by fast ejaculation.
Priligy is used for the treatment of premature ejaculation in adult men between the ages of 18 and 64.
Premature ejaculation occurs when a man ejaculates with reduced sexual urge and before he wants to. This can cause problems for the man and can cause problems during sexual intercourse.
Contraindications When Priligy should not be used
Do not take Priligy:
- If you are allergic to dapoxetine or any of the ingredients of this medicine
- If you have heart problems, such as heart failure or heart rhythm problems.
- If you have problems with fainting
- If you have ever had a history of mania (symptoms including overexcitement, irritation or confusion) or severe depression.
If you are taking:
- medicines for depression, called "mono-amino oxidase inhibitors" (MAOIs)
- thioridazine used for schizophrenia
- other medications for depression
- lithium, a drug for bipolar disorder
- linezolid, an antibiotic used to treat infections
- tryptophan, a sleeping pill
- St. John's wort, a herbal medicine
- tramadol, used to treat severe pain
- medicines used to treat migraines.
Do not take Priligy together with any of the medicines listed above.
If you have taken any of these medicines, you will need to wait 14 days after stopping them before you can take Priligy. After stopping Priligy, you will have to wait 7 days before taking any of the medicines listed above. If you are not sure, ask your doctor or pharmacist before taking this medicine (see section "Other medicines and Priligy").
- certain medicines for fungal infections, including ketoconazole and itraconazole (see section "Other medicines and Priligy")
- certain HIV medicines, including ritonavir, saquinavir, nelfinavir and atazanavir (see section "Other medicines and Priligy")
- certain antibiotics for the treatment of infections, including telithromycin (see section "Other medicines and Priligy")
- nefazodone, an antidepressant (see section "Other medicines and Priligy")
- have moderate or severe liver problems.
Do not take this medicine if any of the above applies to you. If you are not sure, ask your doctor or pharmacist before taking this medicine
Precautions for use What you need to know before taking Priligy
Talk to your doctor, pharmacist or nurse before taking Priligy if:
- she was not diagnosed with "premature ejaculation."
- have another sexual problem, such as erectile dysfunction
- have a history of dizziness as a result of low blood pressure
- uses recreational drugs, such as ecstasy, LSD, narcotics, or benzodiazepines
- drink alcohol (see section "Priligy with food, drink and alcohol")
- have had a mental health problem, such as depression, mania (symptoms include feeling overexcited, irritability or inability to think clearly), bipolar disorder (symptoms include severe mood swings between mania and depression) or schizophrenia (an illness psychiatric)
- is suffering from epilepsy
- have a history of bleeding or blood clotting problems
- have kidney problems
- have or are at risk for high pressure in the eyes (glaucoma).
If any of the above apply to you (or if you are not sure), talk to your doctor or pharmacist before taking this medicine. Before you start taking this medicine, your doctor should do a test to make sure your blood pressure doesn't drop too much when you go from lying down to standing upright.
Children and adolescents
This medicine should not be used in children and adolescents under the age of 18.
Interactions Which drugs or foods can change the effect of Priligy
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription and herbal medicines.
This is because Priligy can affect the way other drugs work, just as other drugs can affect the way Priligy works. Therefore, the use of other medicines may affect the maximum dose of Priligy that you are allowed to take.
Do not take Priligy together with any of the following medicines:
- Medicines for depression, called "mono-amino oxidase inhibitors" (MAOIs)
- Thioridazine used for schizophrenia
- Other medications for depression
- Lithium, a drug for bipolar disorder
- Linezolid, an antibiotic used to treat infections
- Tryptophan, a sleeping pill
- St. John's wort, a herbal medicine
- Tramadol, used for the treatment of severe pain
- Medicines used to treat migraines.
Do not take Priligy together with any of the medicines listed above. If you have taken any of these medicines, you will need to wait 14 days after stopping it before you can take Priligy. After stopping Priligy, you will have to wait 7 days before taking any of the medicines listed above. If you are not sure, ask your doctor or pharmacist before taking this medicine.
- Certain medicines for fungal infections, including ketoconazole and itraconazole
- Certain HIV medicines, including ritonavir, saquinavir, nelfinavir and atazanavir
- Certain antibiotics to treat infections, including telithromycin
- Nefazodone, an antidepressant.
Tell your doctor or pharmacist if you are taking any of the following medicines:
- Medicines for mental health problems other than depression.
- Non-steroidal anti-inflammatory drugs, such as ibuprofen or acetylsalicylic acid.
- Anticoagulant drugs, such as warfarin.
- Some medicines used to treat erectile dysfunction, such as sildenafil, tadalafil and vardenafil, as these drugs can lower blood pressure when standing up.
- Some medicines used to treat high blood pressure and chest pain (angina) (such as verapamil and diltiazem), or an enlarged prostate, as these medicines can also lower your blood pressure when standing up.
- Certain other medicines for fungal infections, such as fluconazole.
- Certain other HIV medicines, such as amprenavir and fosamprenavir.
- Certain other antibiotics for the treatment of infections, such as erythromycin and clarithromycin.
- Apripitant, used to treat nausea.
If you are not sure if any of the above points apply to you, talk to your doctor or pharmacist before taking this medicine.
Priligy with food, drink and alcohol
- This medicine can be taken with or without meals.
- You must take this medicine with at least a full glass of water.
- Avoid alcohol when taking tablets of this medicine.
- The effects of alcohol, such as dizziness, sleepiness and slow reactions, may be worsened if you also take this medicine.
- Using alcohol while taking this medicine may increase the risk of injury from fainting or other side effects.
Warnings It is important to know that:
Pregnancy, breastfeeding and fertility
The use of this medicine is not indicated in women.
Driving and using machines
You may feel sleepy, dizzy, faint, have difficulty concentrating and have blurred vision while taking this medicine. Do not drive or use dangerous machinery, if you have any of these or similar effects. The effects of alcohol may increase if you also take this medicine and you may be more at risk of injury from fainting or other side effects if you take this medicine with alcohol.
Priligy contains lactose
This medicine contains lactose (a type of sugar). If your doctor has told you that you have an "intolerance to some sugars, contact your doctor before taking this medicine.
Dose, Method and Time of Administration How to use Priligy: Posology
Always take this medicine exactly as your doctor or pharmacist has told you.
If in doubt, consult your doctor or pharmacist.
- The recommended dose is 30 mg. Your doctor may increase the dose to 60 mg.
- Take this medicine only 1 to 3 hours before sexual activity.
- Do not take this medicine more than once every 24 hours or every day.
- Swallow the tablets whole, to avoid a bitter taste, with at least a full glass of water. This may reduce the possibility of fainting (see "Fainting and low blood pressure")
- This medicine can be taken with or without meals.
- This medicine should not be used by men under the age of 18 or aged 65 or over.
- Review your Priligy treatment with your doctor after the first 4 weeks or after 6 doses to see if you need to continue treatment. If treatment is continued, you should review therapy with your doctor at least every six months.
Overdose What to do if you have taken too much Priligy
If you take more Priligy than you should
If you take more tablets than you should, please tell your doctor or pharmacist. You may feel nauseous or vomit.
If you stop taking Priligy
Talk to your doctor before stopping treatment with this medicine. You may have trouble sleeping and feel dizzy after stopping treatment with this medicine, even if you have not taken it every day.
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse
Side Effects What are the side effects of Priligy
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop taking Priligy and contact your doctor immediately if
- has seizures
- faints or has a light-headed feeling when standing up
- notice any change in mood
- have thoughts of killing or harming yourself.
If you notice any of the side effects listed above, stop taking Priligy and contact your doctor immediately.
Fainting and low blood pressure
This medicine can cause fainting or lower blood pressure when standing up. To reduce the chance of this happening:
- take this medicine with at least one full glass of water
- do not take this medicine if you are dehydrated (you do not have enough water in your body).
This can happen if:
- hasn't drunk anything in the last 4-6 hours,
- has been sweating for a long time,
- have an illness with a high temperature, diarrhea or vomiting.
- If you feel faint (for example, feel sick, dizzy, light-headed, confused, sweating or have an irregular heartbeat) or feel light-headed when standing up, lie down immediately, so whether your head is lower than the rest of your body or sit with your head between your knees until you feel better. This will prevent you from falling and injuring yourself if you faint.
- Don't get up quickly after sitting or lying down for a long time.
- Do not drive or use any tools or machines if you feel faint while taking this medicine.
- Tell your doctor if you pass out while taking Priligy.
Very common side effects (may affect more than 1 in 10 patients):
- feeling dizzy
- headache
- feeling nauseous.
Common side effects (may affect up to 1 in 10 patients):
- feeling irritable, anxious, agitated or restless
- feeling numb with "tingling"
- difficulty getting an erection or maintaining it
- sweating more than normal or hot flashes
- diarrhea, constipation or flatulence
- stomach pain, bloating or vomiting
- insomnia or strange dreams
- feeling tired or sleepy, yawning
- stuffy nose (nasal congestion)
- increased blood pressure
- difficulty concentrating
- chills or tremors
- reduced interest in sexuality
- ringing in the ears
- blurred vision
- indigestion
- dry mouth.
Uncommon side effects (may affect up to 1 in 100 people):
- fainting or dizziness upon getting up (see above)
- change in mood, feeling overexcited or paranoia
- feeling confused, disoriented or unable to think clearly
- slow or irregular heartbeat or rapid heart rate
- loss of sexual urge, trouble reaching orgasm
- feeling of weakness, exhaustion, lethargy or tiredness
- feeling depressed, nervous or indifferent
- feeling hot, agitated, weird, or intoxicated
- vision problems, eye pain or dilated pupils
- low or high blood pressure
- feeling itchy or cold sweat
- sense of dizziness
- change in taste
- teeth grinding.
Rare side effects (may affect up to 1 in 1,000 patients):
- feeling dizzy after exertion
- sudden falls asleep
- urgent defecation.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system at: https: // www. .aifa.gov.it / content / adverse-reaction-reports By reporting side effects you can help provide more information on the safety of this medicine.
Expiry and Retention
- This medicine does not require any special storage conditions.
- Keep this medicine out of the sight and reach of children.
- Do not use this medicine after the expiry date which is stated on the carton after "EXP". The expiry date refers to the last day of the month.
- 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.
Contents of the pack and other information
What Priligy contains
The active ingredient is dapoxetine. Each tablet contains 30 mg or 60 mg of dapoxetine as the hydrochloride salt.
The excipients are:
- Tablet core: lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, colloidal anhydrous silica, magnesium stearate.
- Tablet coating: lactose monohydrate, hypromellose, titanium dioxide (E171), triacetin, black iron oxide (E172), yellow iron oxide (E172).
Description of what Priligy looks like and contents of the pack
Priligy 30 mg film-coated tablets are light gray, round, convex, approximately 6.5 mm in diameter and marked with "30" inside a triangle on one side.
Priligy 60 mg film-coated tablets are gray, round, convex, approximately 8 mm in diameter and are marked with "60" on one side within a triangle. The tablets are supplied in multi-layer blister packs containing 1, 2, 3 or 6 film-coated tablets.
Not all pack sizes may be marketed
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
PRILIGY TABLETS COATED WITH FILM
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains dapoxetine hydrochloride, equivalent to 30 mg or 60 mg of dapoxetine.
Excipient with known effect: lactose. Each 30 mg tablet contains 45.88 mg of lactose. Each 60 mg tablet contains 91.75 mg of lactose.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Film-coated tablet.
The 30 mg film-coated tablets are light gray, round, convex, approximately 6.5 mm in diameter and debossed with "30" inside a triangle on one side.
The 60 mg film-coated tablets are gray, round, convex, approximately 8 mm in diameter and debossed with "60" inside a triangle on one side.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Priligy is indicated for the treatment of premature ejaculation (PE) in adult men aged 18 to 64 years.
Priligy should only be prescribed to patients who meet all of the following criteria:
• Intravaginal ejaculatory latency time (intravaginal ejaculatory latency time - IELT) less than two minutes; And
• Persistent or recurrent ejaculation at the slightest sexual stimulation, before, during or just after penetration and before the patient wishes; And
• Significant personal distress or interpersonal difficulty resulting from PE; e
• Poor control of ejaculation;
• A history of premature ejaculation in most sexual intercourse in the previous 6 months.
Priligy should only be given as an on-demand treatment prior to anticipated sexual activity. Priligy should not be prescribed to delay ejaculation in men who have not been diagnosed with PE.
04.2 Posology and method of administration
Dosage
Adult men (aged 18-64)
The recommended starting dose for all patients is 30 mg, taken as needed, approximately 1 to 3 hours before sexual activity. Priligy treatment should not be started with the 60 mg dose.
Priligy is not intended for continued daily use. Priligy should only be taken when sexual activity is anticipated. Priligy should not be taken more than once in 24 hours.
If the individual response to the 30 mg dose is insufficient and the patient has shown no moderate or severe adverse reactions or prodromal symptoms suggestive of syncope, the dose can be increased to the maximum recommended 60 mg, taken as needed from 1 to 3 hours before sexual activity. The incidence of adverse events is higher with the 60 mg dose.
If the patient experienced orthostatic reactions at the starting dose, the dose should not be increased to 60 mg (see section 4.4).
A careful evaluation of the risks and benefits of Priligy should be made by your doctor after the first four weeks of treatment (or after at least 6 doses of treatment), to decide whether it is appropriate to continue treatment with Priligy.
Data on the efficacy and safety of Priligy beyond 24 weeks are limited. The clinical need for continued treatment and the benefit / risk ratio of Priligy should be reassessed at least every six months.
Elderly (aged 65 years and over)
The efficacy and safety of Priligy have not been established in patients 65 years of age and older (see section 5.2).
Pediatric population
Given the premature ejaculation indication Priligy is not intended for use in this population.
Patients with renal dysfunction
Caution is advised in patients with mild or moderate renal dysfunction. The use of Priligy is not recommended in patients with severe renal dysfunction (see sections 4.4 and 5.2).
Patients with hepatic dysfunction
The use of Priligy is contraindicated in patients with moderate and severe hepatic dysfunction (Child-Pugh class B and C) (see sections 4.3 and 5.2).
Poor metabolisers of CYP2D6 or patients treated with potent CYP2D6 inhibitors
Caution is advised if the dose is increased to 60 mg in patients known to belong to the CYP2D6 poor metabolisers genotype or in patients receiving concomitant treatment with potent CYP2D6 inhibitors (see sections 4.4, 4.5 and 5.2).
Patients treated with potent or moderate CYP3A4 inhibitors
Concomitant use of potent CYP3A4 inhibitors is contraindicated. In patients receiving concomitant treatment with moderate CYP3A4 inhibitors the dose should be limited to 30 mg and caution is recommended (see sections 4.3, 4.4 and 4.5).
Method of administration
For oral use. The tablets should be swallowed whole to avoid a bitter taste. It is recommended that the tablets be taken with at least a full glass of water. Priligy can be taken with or without meals (see section 5.2).
Precautions to be taken before handling or administering the medicinal product
Before starting treatment, see section 4.4 regarding orthostatic hypotension.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Significant pathological conditions affecting the heart such as:
• Heart failure (NYHA class II-IV)
• Conduction abnormalities such as AV block or sick sinus syndrome
• Significant ischemic heart disease
• Significant valvular heart disease.
• History of syncope.
History of mania or severe depression.
Concomitant treatment with mono-amino oxidase inhibitors (MAOIs), or within 14 days of stopping treatment with a MAOI. Similarly, no MAOIs should be given within 7 days of stopping Priligy (see section 4.5). .
Concomitant treatment with thioridazine, or within 14 days of stopping treatment with thioridazine. Similarly, thioridazine should not be administered within 7 days of stopping treatment with Priligy (see section 4.5).
Concomitant treatment with selective serotonin reuptake inhibitors (selective serotonin reuptake inhibitors - SSRIs), serotonin and noradrenaline reuptake inhibitors (serotonin-norepinephrine reuptake inhibitors - SNRI), tricyclic antidepressants (tricyclic antidepressants- TCA) or other medicinal / herbal products with a serotonergic effect [eg. L-tryptophan, triptans, tramadol, linezolid, lithium, St. John's wort (Hypericum perforatum)] or within 14 days of stopping treatment with these medicinal / herbal products. Similarly, these medicinal / herbal products should not be administered within 7 days of stopping treatment with Priligy (see section 4.5).
Concomitant treatment with potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nelfinavir, atazanavir, etc. (see section 4.5).
Moderate and severe hepatic dysfunction.
04.4 Special warnings and appropriate precautions for use
General recommendations
Priligy is only indicated in men with premature ejaculation who meet all the criteria listed in sections 4.1 and 5.1. Priligy should not be prescribed to men who have not been diagnosed with premature ejaculation. The safety profile has not been established and there are no data on delayed ejaculation in men without premature ejaculation.
Other forms of sexual dysfunction
Before treatment, people with other forms of sexual dysfunction, including erectile dysfunction, should be carefully examined by their doctor. Priligy must not be used in men with erectile dysfunction (ED) who are using PDE5 inhibitors (see section 4.5).
Orthostatic hypotension
Before initiating therapy, the physician must perform a "careful examination, including evaluation in history of orthostatic events. An orthostatic test (blood pressure and pulse in supine and standing positions) should be performed before starting therapy. history of orthostatic reaction (documented or suspected), treatment with Priligy should be avoided.
Orthostatic hypotension has been reported in clinical studies. The attending physician should first inform the patient that in case of possible prodromal symptoms, such as feeling lightheaded immediately after standing up, he should immediately lie down so that his head is lower than the rest of the body or sit with his head between his legs. knees until symptoms go away. The attending physician should also advise the patient not to get up quickly after lying or sitting for a long time.
Suicide / suicidal thoughts
Compared to placebo, antidepressants, including SSRIs, increased the risk of suicidal thoughts and suicidal tendencies in short-term studies in children and adolescents with major depressive disorder and other psychiatric disorders. Short-term studies have shown no increased risk of suicidal tendencies in adults over 24 years of age taking antidepressants compared to placebo. In the clinical trials of Priligy, for the treatment of premature ejaculation, there was no clear-cut evidence of treatment-associated suicidal tendencies in the assessment of possibly suicide-related adverse events as assessed by the Columbia Classification Suicide Assessment Algorithm (C- CASA), Montgomery-Asberg Depression Rating Scale, or Beck Depression Inventory-II.
Syncope
Patients should be advised to avoid situations in which possible injury may occur, including driving or operating dangerous machinery, due to syncope or any of its prodromal symptoms such as dizziness or lightheadedness (see section 4.8).
Potentially prodromal symptoms such as nausea, dizziness / lightheadedness and diaphoresis were reported more frequently among patients treated with Priligy than in those in the placebo group. In clinical studies, cases of syncope, defined as loss of consciousness, with bradycardia or sinus arrest observed in patients monitored with Holter devices, were believed to be of vasovagal aetiology and most occurred within the first 3 hours of taking the drug. after the first dose or in association with clinical study-related procedures (such as blood sampling, orthostatic maneuvers, blood pressure measurements) Possible prodromal symptoms, such as nausea, dizziness, lightheadedness, palpitations, asthenia, confusion and diaphoresis yes they usually occur within the first 3 hours of taking the drug and often precede syncope. Patients should be informed of the possibility of developing syncope, with or without prodromal symptoms, at any time during their treatment with Priligy. Treating physicians should educate patients on the importance of maintaining adequate hydration and how to recognize prodromal signs and symptoms to reduce the likelihood of serious injury associated with falls due to loss of consciousness. If the patient experiences possible prodromal symptoms, he should immediately lie down so that his head is lower than the rest of the body or sit with his head between his knees until the symptoms disappear and pay attention to situations where it could cause damage. including driving and operating hazardous machinery if syncope or other CNS effects occur (see section 4.7).
Patients with cardiovascular risk factors
Subjects with underlying cardiovascular disease were excluded from Phase 3 clinical trials. The risk of adverse cardiovascular events resulting from syncope (cardiac syncope and syncope of different aetiology) is increased in patients with underlying structural cardiovascular disease (eg. documented obstruction of outflow, valvular heart disease, carotid stenosis and coronary artery disease). Data are insufficient to determine whether or not this increased risk extends to vasovagal syncope in patients with underlying cardiovascular disease.
Use with recreational drugs (recreational drugs)
Patients should be advised not to take Priligy in combination with recreational drugs (recreational drugs).
Recreational drugs with serotonergic activity such as ketamine, methylenedioxymethamphetamine (MDMA) and lysergic acid diethylamide (lysergic acid diethylamide - LSD) can lead to potentially serious reactions when associated with Priligy. These reactions include, but are not limited to, arrhythmia, hyperthermia and serotonin syndrome. The use of Priligy with recreational drugs with sedative properties, such as narcotics and benzodiazepines, may further increase sleepiness and dizziness.
Ethanol
Patients should be advised not to use Priligy in combination with alcohol.
The combination of alcohol and dapoxetine may increase the neurocognitive effects of alcohol and may also increase neurocardiogenic adverse events such as syncope, thereby increasing the risk of accidental injury. Patients are therefore recommended to avoid drinking alcohol while taking Priligy (see sections 4.5 and 4.7).
Medicines with vasodilating properties
Priligy should be prescribed with caution in patients taking medicinal products that have vasodilatory properties (such as alpha adrenergic and nitrate receptor antagonists) due to the possible reduction of orthostatic tolerance (see section 4.5).
Moderate CYP3A4 inhibitors
Caution is advised in patients taking moderate CYP3A4 inhibitors and the dose should be limited to 30 mg (see sections 4.2 and 4.5).
Potent CYP2D6 inhibitors
Caution is advised if the dose is increased to 60 mg in patients taking potent CYP2D6 inhibitors or if the dose is increased to 60 mg in patients known to belong to the CYP2D6 poor metabolisers genotype, as this may increase drug exposure. and hence the incidence and severity of dose-dependent adverse events (see sections 4.2, 4.5 and 5.2).
Mania
Priligy should not be used in patients with a history of mania / hypomania or bipolar disorder and should be discontinued in those patients who develop symptoms of these disorders.
Seizures
Due to the potential ability of SSRIs to reduce the seizure threshold, Priligy should be discontinued in patients who develop seizures and avoided in patients with unstable epilepsy. Patients with controlled epilepsy should be carefully monitored.
Pediatric population
Priligy should not be used in patients under the age of 18.
Depression and / or psychiatric disorders
Men with underlying depressive signs and symptoms should be evaluated before prescribing Priligy treatment to rule out undiagnosed depressive disorders. Concomitant treatment of Priligy and antidepressants, including SSRIs and SNRIs, is contraindicated (see section 4.3). It is not recommended to discontinue current treatment for depression or anxiety in order to initiate administration of Priligy for the treatment of PE. Priligy is not indicated for psychiatric disorders and should not be used in men with disorders such as schizophrenia, or in those with concomitant depression, as worsening symptoms associated with depression cannot be excluded. This could be the result of an underlying psychiatric disorder or drug therapy. Physicians should encourage patients to report any distressing thoughts or feelings at any time and if depressive signs and symptoms occur during treatment, Priligy should be discontinued.
Hemorrhage
Abnormal bleeding has been reported with SSRIs. Therefore, caution should be exercised in patients taking Priligy, especially in combination with medicinal products known to have an effect on platelet function (e.g. atypical antipsychotics and phenothiazines, acetylsalicylic acid, non-steroidal anti-inflammatory drugs [NSAIDs], antiplatelet agents) or anticoagulants (eg warfarin), as well as in patients with a "history of bleeding or bleeding disorders (see section 4.5).
Renal dysfunction
The use of Priligy is not recommended in patients with severe renal dysfunction and caution is advised in patients with mild or moderate renal dysfunction (see sections 4.2 and 5.2).
Dosing interruption effects
Abrupt discontinuation of chronically administered SSRIs used to treat chronic depressive disorders has been reported to generate the following symptoms: dysphoria, irritability, agitation, dizziness, sensory disturbances (eg paraesthesia, such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia and hypomania.
A double-blind clinical study conducted in patients with PE evaluating the effects of discontinuing therapy after 62 days of daily or reliever administration of a 60 mg dose of Priligy revealed mild withdrawal symptoms with a "slightly higher incidence for insomnia and dizziness in patients who switched from daily dosing to placebo (see section 5.1).
Eye disorders
The use of Priligy has been associated with ocular effects such as mydriasis and ocular pain. Priligy should be used with caution in patients with increased intraocular pressure or at risk of narrow-angle glaucoma.
Lactose intolerance
Patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption should not take this drug.
04.5 Interactions with other medicinal products and other forms of interaction
Pharmacodynamic interactions
Possibility of interaction with mono-amino-oxidase inhibitors
Among patients taking an SSRI in combination with a monoamine oxidase inhibitor (MAOI), there have been reports of severe, sometimes fatal reactions, including hyperthermia, rigidity, myoclonia, autonomic instability with possible rapid fluctuations in vital signs and changes in mental status, which include extreme agitation that can lead to delirium and coma. These reactions have also been reported in patients who started taking a MAOI soon after stopping an SSRI. Some cases presented with characteristics similar to neuroleptic malignant syndrome. Animal data on the effects of combining an SSRI and a MAOI indicate that these medicinal products may work synergistically by increasing blood pressure and evoking behavioral arousal. Therefore, Priligy should not be taken in conjunction with a MAOI, or within 14 days of stopping treatment with a MAOI Similarly, a MAOI should not be given within 7 days of stopping treatment with Priligy (see section 4.3).
Possibility of interaction with thioridazine
Individually administered thioridazine produces QTc interval prolongation associated with severe ventricular arrhythmias. Medicinal products such as Priligy that inhibit the CYP2D6 isoenzyme appear to inhibit the metabolism of thioridazine and the resulting increase in thioridazine levels is believed to increase the QTc interval prolongation. Priligy should not be used in combination with thioridazine or within 14 days of stopping treatment with thioridazine. Similarly, thioridazine should not be administered within 7 days of stopping treatment with Priligy (see section 4.3).
Medicinal / herbal products with serotonergic effect
Similarly to other SSRIs, co-administration of serotonergic medicinal / herbal products (including MAOIs, L-tryptophans, triptans, tramadol, linezolid, SSRIs, SNRIs, lithium and St. John's wort preparations (Hypericum perforatum)) can lead to effects associated with serotonin. Priligy must not be used in combination with other SSRIs, MAOIs or other serotonergic medicinal / herbal products or within 14 days of stopping treatment with these medicinal / herbal products. Similarly, these medicinal / herbal products should not be administered within 7 days of stopping treatment with Priligy (see section 4.3).
Medicinal products with CNS effect
The use of Priligy in combination with medicinal products with CNS effect (eg antiepileptics, antidepressants, antipsychotics, anxiolytics, sedative hypnotics) has not been systematically evaluated in patients with premature ejaculation. Therefore, caution is recommended if necessary. co-administer Priligy and such drugs.
Pharmacokinetic interactions
Effects of co-administration of medicinal products on the pharmacokinetic profile of dapoxetine
Education in vitro conducted on human liver, kidney and intestinal microsomes indicate that dapoxetine is metabolised primarily by CYP2D6, CYP3A4 and flavin monooxygenase 1 (FMO1). Therefore, inhibitors of these enzymes can reduce the clearance of dapoxetine.
CYP3A4 inhibitors
Potent CYP3A4 inhibitors.
Administration of ketoconazole (200 mg twice daily for 7 days) increased the Cmax and AUCinf of dapoxetine (60 mg single dose) by 35% and 99%, respectively. Taking into account the contribution of both the free fraction of dapoxetine and desmethyldapoxetine, the Cmax of the active fraction can increase by approximately 25% and the AUC of the active fraction can double if potent inhibitors of CYP3A4 are taken.
The increase in Cmax and AUC of the active fraction may increase markedly in the population segment that exhibits functional loss of CYP2D6, ie CYP2D6 poor metabolisers, or when the drug is combined with potent CYP2D6 inhibitors.
Therefore, concomitant use of Priligy and potent CYP3A4 inhibitors, such as ketoconazole, itraconazole, ritonavir, saquinavir, telithromycin, nefazodone, nelfinavir and atazanavir is contraindicated (see section 4.3).
Moderate CYP3A4 inhibitors.
Concomitant use of moderate CYP3A4 inhibitors (ie erythromycin, clarithromycin, fluconazole, amprenavir, fosamprenavir, aprepitant, verapamil, diltiazem) may also result in a significant increase in exposure to dapoxetine and desmethyldapoxetine, especially in CYP2D6 poor metabolisers If dapoxetine is combined with any of these drugs, the maximum dose of dapoxetine should be 30 mg (see sections 4.2, 4.4 and following).
These measures apply to all patients unless it has been verified by genotyping or phenotyping that the patient is a rapid metaboliser of CYP2D6. In patients found to be extensive metabolisers of CYP2D6, a maximum dose of 30 mg is recommended if dapoxetine is combined with a potent CYP3A4 inhibitor and caution is advised if dapoxetine is taken in doses of 60 mg together with a moderate CYP3A4 inhibitor. .
Potent CYP2D6 inhibitors
Cmax and AUCinf of dapoxetine (60 mg single dose) increased by 50% and 88%, respectively, in the presence of fluoxetine (60 mg /die for 7 days). Taking into account the contribution of both the free fraction of dapoxetine and desmethyldapoxetine, the Cmax of the active fraction can increase by approximately 50% and the AUC of the active fraction can double, if potent inhibitors of CYP2D6 are taken. These increases in Cmax and AUC of the active fraction are similar to those expected for CYP2D6 poor metabolisers and may result in a higher incidence and severity of dose-dependent adverse events (see section 4.4).
PDE5 inhibitors
Priligy must not be administered in patients taking PDE5 inhibitors due to a possible reduction in orthostatic tolerance (see section 4.4). The pharmacokinetic profile of dapoxetine (60 mg) in combination with tadalafil (20 mg) and sildenafil (100 mg) was evaluated in a study crossover with single dose. Tadalafil does not affect the pharmacokinetic profile of dapoxetine. Sildenafil caused slight changes in the pharmacokinetic profile of dapoxetine (22% increase in AUCinf and 4% in Cmax), not considered clinically significant.
Concomitant use of Priligy with PDE5 inhibitors may cause orthostatic hypotension (see section 4.4). The efficacy and safety of Priligy in patients with premature ejaculation and concomitant erectile dysfunction treated concomitantly with Priligy and PDE5 inhibitors have not been established. .
Effects of dapoxetine on the pharmacokinetic profile of concomitantly administered medicinal products
Tamsulosin
Co-administration of single or multiple doses of dapoxetine of 30 mg or 60 mg to patients taking tamsulosin daily did not result in changes in the pharmacokinetic profile of tamsulosin. Co-administration of dapoxetine and tamsulosin did not change the orthostatic profile and there were no differences in orthostatic effects between tamsulosin combined with 30 or 60 mg doses of dapoxetine and tamsulosin administered alone. However, Priligy should be prescribed with caution to patients taking alpha-adrenergic receptor antagonists due to a possible reduction in orthostatic tolerance (see section 4.4).
Medicinal products metabolised by CYP2D6
Multiple doses of dapoxetine (60 mg /die for 6 days) followed by a single 50 mg dose of desipramine, increased the average Cmax and AUC of desipramine by approximately 11% and 19%, respectively, compared with single administration of desipramine. Dapoxetine may result in a similar increase in plasma concentrations of drugs metabolised by CYP2D6. Clinical relevance is likely to be small.
Medicinal products metabolised by CYP3A
Multiple doses of dapoxetine (60 mg /die for 6 days) reduced the AUC of midazolam (8 mg single dose) by approximately 20% (range -60 to + 18%). The clinical relevance of the effect on midazolam is likely to be small in most patients . The increased CYP3A activity may be of clinical relevance in some patients concomitantly treated with a medicinal product metabolised primarily by CYP3A and with a narrow therapeutic window.
Medicinal products metabolised by CYP2C19
Multiple doses of dapoxetine (60 mg /die for 6 days) did not inhibit the metabolism of a single 40 mg dose of omeprazole. Dapoxetine is unlikely to affect the pharmacokinetic profile of other CYP2C19 substrates.
Medicinal products metabolised by CYP2C9
Multiple doses of dapoxetine (60 mg /die for 6 days) did not affect the pharmacokinetic or pharmacodynamic profile of a single 5 mg glyburide dose. Dapoxetine is unlikely to affect the pharmacokinetic profile of other CYP2C9 substrates.
Warfarin and medicines known to affect blood clotting and / or platelet function
There are no data evaluating the effect of chronic use of warfarin with dapoxetine. Therefore, caution should be exercised when dapoxetine is administered to patients chronically taking warfarin (see section 4.4). In a pharmacokinetic study, dapoxetine (60 mg /diefor 6 days) did not affect the pharmacokinetic or pharmacodynamic (PT or INR) profile of warfarin after a single 25 mg dose.
Cases of abnormal bleeding have been reported with SSRIs (see section 4.4)
Ethanol
Co-administration of a single dose of ethanol, 0.5 g / kg (approximately 2 glasses of alcoholic beverages), does not affect the pharmacokinetic profile of dapoxetine (60 mg single dose). However, dapoxetine in combination with ethanol increases sleepiness and significantly reduces the feeling of alertness. Pharmacodynamic measurements of cognitive impairment (Digit Vigilance Speed, Digit Symbol Substitution Test) also showed an additive effect, when Priligy was co-administered with ethanol. Concomitant use of alcohol and dapoxetine increases the chance of adverse reactions such as dizziness, sleepiness, slow reflexes, or impaired judgment, or increases their severity. The combination of alcohol and dapoxetine may enhance these alcohol-related effects and it can also exacerbate neurocardiogenic adverse events such as syncope, thereby increasing the risk of accidental injury. Patients should therefore be advised to avoid alcohol intake when taking Priligy (see sections 4.4 and 4.7).
04.6 Pregnancy and lactation
Priligy is not indicated for use in women.
Animal studies do not indicate direct or indirect harmful effects with respect to fertility, pregnancy or embryonal / fetal development (see section 5.3).
It is unknown whether dapoxetine or its metabolites are excreted in human milk.
04.7 Effects on ability to drive and use machines
Priligy has little or moderate influence on the ability to drive and use machines. In clinical studies, dizziness, disturbance in attention, syncope, blurred vision and somnolence were reported in patients taking dapoxetine. Therefore, patients should be cautioned to avoid situations that could cause harm, including driving or using dangerous machinery.
The combination of alcohol and dapoxetine may enhance alcohol-related neurocognitive effects and may also exacerbate neurocardiogenic adverse events such as syncope, thereby increasing the risk of accidental injury. Patients should therefore be advised to avoid alcohol intake when taking Priligy (see sections 4.4 and 4.5).
04.8 Undesirable effects
Summary of the safety profile
In clinical studies, syncope and orthostatic hypotension have been reported (see section 4.4).
The following adverse reactions were reported most commonly during Phase III clinical trials and were found to be dose related: nausea (11.0% and 22.2%, respectively, in the groups of patients who received dapoxetine 30 mg and dapoxetine 60 mg as needed. ), dizziness (5.8% and 10.9%), headache (5.6% and 8.8%), diarrhea (3.5% and 6.9%), insomnia (2.1% and 3, 9%) and fatigue (2.0% and 4.1%). The most common adverse events leading to treatment discontinuation were nausea (2.2% of Priligy-treated patients) and dizziness (1.2% of Priligy-treated patients).
Summary table of adverse reactions
The safety of Priligy was evaluated in 4,224 premature ejaculation patients who participated in five double-blind, placebo-controlled clinical trials. Out of 4,224 patients, 1,616 patients received a 30 mg dose of Priligy as needed and 2,608 received a 60 mg dose of Priligy, either as needed or once daily.
Table 1 illustrates the adverse reactions that have been reported.
Adverse reactions reported in the 9-month, long-term, open-label extension of one study were consistent with those reported in the double-blind studies and no additional adverse drug reactions were reported.
Description of selected adverse reactions
Syncope, defined as loss of consciousness, with bradycardia or sinus arrest observed in patients with Holter monitors, has been reported in clinical trials and is considered drug related. Most cases occurred during the first 3 hours after administration, after the first dose, or associated with study-related clinical procedures (such as blood sampling, orthostatic maneuvers, and blood pressure measurements). Prodromal symptoms often preceded syncope (see section 4.4).
The occurrence of syncope and possible prodromal symptoms appears to be dose-dependent, as evidenced by the higher incidence among patients treated with doses higher than those recommended in Phase 3 clinical trials.
Orthostatic hypotension has been reported in clinical studies (see section 4.4).The frequency of syncope, understood as loss of consciousness, in the Priligy clinical development program varies according to the population studied and ranges from 0.06% (30 mg) to 0.23% (60 mg) for enrolled patients in Phase 3 placebo-controlled clinical trials, and 0.64% (all doses combined) in Phase 1 clinical trials in healthy volunteers who do not have PE.
Other special populations
Caution is advised if the dose is increased to 60 mg in patients taking strong inhibitors of CYP2D6 or in patients poor metabolisers of CYP2D6 (see sections 4.2, 4.4, 4.5 and 5.2).
Suspension Effects
Abrupt discontinuation of chronically administered SSRIs used to treat chronic depressive disorders has been reported to generate the following symptoms: dysphoria, irritability, agitation, dizziness, sensory disturbances (e.g. paraesthesia such as electric shock sensations), anxiety, confusion , headache, lethargy, emotional lability, insomnia and hypomania.
The results of a safety study showed a slightly higher incidence for withdrawal effects such as mild or moderate insomnia and dizziness in patients who switched from daily dosing to placebo after 62 days of dosing.
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 the national reporting system. "address: http://www.agenziafarmaco.gov.it/it/responsabili
04.9 Overdose
No cases of overdose have been reported.
In a clinical pharmacology study with Priligy, no unexpected adverse events occurred with daily doses up to 240 mg (two 120 mg doses given 3 hours apart). Generally, SSRI overdose symptoms include serotonin-mediated adverse reactions such as somnolence, gastrointestinal disturbances such as nausea and vomiting, tachycardia, tremor, agitation and dizziness.
In cases of overdose, standard supportive measures should be employed if necessary. Due to the high protein binding and large volume of distribution of dapoxetine hydrochloride, forced diuresis, dialysis, haemoperfusion and transfusion exchange are unlikely to be beneficial. There is no known specific antidote for Priligy.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Other Urologicals, ATC code: G04BX14
Mechanism of action
Dapoxetine is a potent selective serotonin reuptake inhibitor (SSRI) with an IC50 of 1.12 nM, while its major human metabolites, desmethyldapoxetine (IC50
Human ejaculation is primarily mediated by the sympathetic nervous system. The ejaculatory process originates from a brain stem mediated spinal reflex center, which is initially influenced by numerous brain nuclei (median preoptic nucleus and paraventricular nucleus).
It is assumed that the mechanism of action of dapoxetine in premature ejaculation is related to the inhibition of neuronal reuptake of serotonin and the consequent enhancement of the action of the neurotransmitter on pre- and postsynaptic receptors.
In the rat, dapoxetine inhibits the ejaculatory expulsion reflex by acting at the supraspinal level with the lateral paragigantocellular nucleus (LPGi). The sympathetic post-ganglionic nerve fibers, which innervate the seminal vesicles, vas deferens, prostate, bulbourethral muscles and bladder neck. they generate, in a coordinated way, the relative contraction of the innervated organs, to obtain ejaculation. Dapoxetine modulates this ejaculatory reflex in rats.
Clinical efficacy and safety
The efficacy of Priligy in the treatment of premature ejaculation was established in five double-blind, placebo-controlled clinical trials in which a total of 6,081 patients were randomized. Patients had an "age of 18 years or older and a" history of PE in most sexual intercourse in the 6 months prior to enrollment. Premature Ejaculation was defined according to the DSM-IV diagnostic criterion as: time of short intravaginal ejaculatory latency (intravaginal ejaculatory latency time "." IELT; time from vaginal penetration to intravaginal ejaculation) ≤2 minutes measured with a stopwatch in four clinical studies), poor ejaculation control, marked personal discomfort, or interpersonal difficulties due to this condition.
Patients with other forms of sexual dysfunction, including erectile dysfunction, or those using other forms of pharmacotherapy to treat PE, were excluded from all studies.
The results from all RCTs were consistent. Efficacy was demonstrated after 12 weeks of treatment. In one study, European and non-European patients were enrolled for 24 weeks of treatment. In the study, 1,162 patients were randomized, 385 to placebo, 388 to treatment with a 30 mg dose of Priligy as needed and 389 on treatment with a 60 mg dose of Priligy as needed.
The mean and median value of the IELT at the end of the study is shown in Table 2; in Table 3 the cumulative distribution of subjects who achieved at least one specific level in the mean of IELT at the end of the study. Other studies and the combined data analysis at Week 12 gave consistent results.
The extent of IELT prolongation was related to IELT at baseline and was variable between individual subjects. The clinical relevance of the effects of Priligy treatment was further demonstrated in terms of various patient-reported outcome measures and an "analysis of patients who responded to treatment.
A responder was defined as a subject who had an increase of at least 2 categories of ejaculation control plus a reduction of at least 1 category of ejaculation-related discomfort. In each group of patients taking Priligy, a greater percentage Compared to the placebo group, statistically significantly, responded to treatment at the end of the study, week 12 or 24 There was a higher proportion of responders in the dapoxetine 30 mg groups (11.1% - 95% CI [7 , 24; 14.87]) and 60 mg (16.4% - 95% CI [13.01; 19.75]) compared to the placebo group at week 12 (pooled data analysis).
The clinical relevance of the effects of Priligy, by treatment group, is the subject-assessed Global Clinical Impression of Change (CGIC) outcome measure, in which patients were asked to rate their premature ejaculation from the start of the study. , with response options ranging from much better to much worse. At the end of the study (Week 24), 28.4% (30 mg group) and 35.5% (60 mg group) of subjects rated their condition "better" or "much better", compared to 14% of placebo, while 53.4% and 65.6% of subjects treated with dapoxetine 30 mg and 60 mg, respectively, reported that their condition was at least " a little "better", compared to 28.8% for placebo.
05.2 Pharmacokinetic properties
Absorption
Dapoxetine is rapidly absorbed with maximum plasma concentrations (Cmax) occurring approximately 1-2 hours after tablet intake. Absolute bioavailability is 42% (range 15-76%), and proportional increases in plasma are observed. exposure (AUC and Cmax) with increasing dose, between doses of 30 and 60 mg. Following administration of multiple doses, the AUC values for both dapoxetine and its active metabolite desmethyldapoxetine (DED) increase by approximately 50% of single dose AUC values.
Consumption of high-fat meals slightly reduced the Cmax (by 10%) and slightly increased the AUC (by 12%) of dapoxetine and slightly delayed the time to reach peak dapoxetine concentrations. changes are not clinically significant Priligy can be taken with or without meals.
Distribution
More than 99% of dapoxetine is bound in vitro to human serum proteins. The active metabolite, desmethyldapoxetine (DED) is 98.5% protein bound. Dapoxetine has a mean steady-state volume of distribution of 162 L.
Biotransformation
Studies conducted in vitro suggest that dapoxetine is cleared by multiple hepatic and renal enzyme systems, mainly CYP2D6, CYP3A4 and flavin monooxygenase 1 (FMO1). Following oral administration of 14C-labeled dapoxetine, dapoxetine was extensively metabolised to multiple metabolites, mainly via the following biotransformation pathways: N-oxidation, N-demethylation, naphthyl hydroxylation, glucuronidation and sulfation. oral administration, there is evidence of a presystemic first pass metabolism.
Unchanged dapoxetine and dapoxetine-N-oxide were the main circulating molecules in the plasma. Studies in vitro of binding and transport show that dapoxetine-N-oxide is inactive. Other metabolites, including desmethyldapoxetine and didemetildapoxetine, contribute less than 3% of the total circulating drug in plasma. Studies in vitro of binding indicate that DED is equipotent to dapoxetine and that didemetildapoxetine has approximately 50% of the potency of dapoxetine (see section 5.1). The exposure to the unbound fraction of DED (AUC and Cmax) is approximately 50% and 23%, respectively, of the exposure to the free fraction of dapoxetine.
Elimination
The metabolites of dapoxetine are eliminated primarily in the urine as conjugates. The unmodified active molecule was not detected in the urine. Following oral administration, dapoxetine has an initial half-life (distribution) of approximately 1.5 hours, with plasma levels below 5% of peak concentrations at 24 hours post dose and a terminal half-life of approximately 19 hours. The terminal half-life of DED is approximately 19 hours after oral administration.
Pharmacokinetic profile in special populations
The metabolite DED contributes to the pharmacological effect of Priligy, particularly when the concentration of DED increases. The increase of the parameters relating to the active fraction in some special populations is illustrated below. This is the sum of the unbound fraction of dapoxetine and DED. DED is equipotent to dapoxetine. The estimate assumes an equal distribution of DED in the CNS, but it is not known whether this also occurs in this case.
Race
Analyzes of single dose clinical pharmacology studies of 60 mg dapoxetine did not indicate statistically significant differences between the Caucasian, Black, Hispanic and Asian populations. A clinical study conducted to compare the pharmacokinetic profile of dapoxetine in Japanese and Caucasian patients showed 10% to 20% higher plasma levels of dapoxetine (AUC and peak concentration) in Japanese patients due to lower body weight. The slightly higher exposure is not expected to have a clinically significant effect.
Elderly (aged 65 and over)
Analyzes of a single dose clinical pharmacology study of 60 mg dapoxetine revealed no significant differences in pharmacokinetic parameters (Cmax, AUCinf, Tmax) between healthy elderly male and healthy young male subjects. Efficacy and safety have not been established in this population (see section 4.2).
Renal dysfunction
A single dose clinical pharmacology study with a 60 mg dose of dapoxetine was conducted in subjects with mild (CrCL 50 to 80 mL / min), moderate (CrCL 30 to 80 mL / min) renal impairment. There was no clear trend for an increase in dapoxetine AUC to decrease in renal function. The AUC in subjects with severe renal impairment was approximately 2 times that in subjects with normal renal function, although data in patients with severe renal insufficiency are limited. The pharmacokinetics of dapoxetine have not been evaluated in patients requiring renal dialysis (see sections 4.2 and 4.4).
Hepatic dysfunction
In patients with mild hepatic dysfunction, the Cmax of the unbound fraction of dapoxetine decreased by 28% while the AUC was unchanged. The Cmax and AUC of the unbound active fraction (the sum of the exposure to the unbound fraction of dapoxetine and desmethyldapoxetine) was decreased by 30% and 5%, respectively. In patients with moderate hepatic dysfunction, the Cmax of the unbound fraction of dapoxetine remained essentially unchanged (3% decrease) while the AUC increased 66%. The Cmax and AUC of the unbound active fraction are, respectively, unchanged and doubled.
In patients with severe hepatic dysfunction, the Cmax of the unbound fraction of dapoxetine was decreased by 42%, but the AUC was increased by approximately 223%. The Cmax and AUC of the active unbound fraction showed similar changes (see sections 4.2 and 4.3 ).
CYP2D6 polymorphism
In a single dose clinical pharmacology study of 60 mg Priligy, plasma concentrations in CYP2D6 poor metabolisers were higher than those in CYP2D6 extensive metabolisers (approximately 31% increase for Cmax and approximately 36% increase for CYP2D6 AUCinf of dapoxetine and 98% for Cmax and 161% for AUCinf of desmethyldapoxetine). The active fraction of Priligy may be increased by approximately 46% in Cmax and by approximately 90% in AUC. This increase may lead to an increase in the incidence and severity of dose-dependent adverse events (see section 4.2). The safety of Priligy in CYP2D6 poor metabolisers is of particular importance when co-administered with other medicinal products that may inhibit the metabolism of dapoxetine, such as potent and moderate inhibitors of CYP3A4 (see sections 4.2 and 4.3).
05.3 Preclinical safety data
A full evaluation of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, dependence / withdrawal symptoms, phototoxicity and reproductive toxicity of dapoxetine was conducted in conventional preclinical studies (mouse, rat, rabbit, dog and monkey) up to the maximum tolerated dose in each species. In some studies, due to the fact that there is a faster bioconversion in animal species than in humans, the pharmacokinetic exposure indices (Cmax and AUC0-24h) at maximum tolerated doses approached those observed in humans. However, multiple doses normalized to body weight were 100 times higher. No clinically relevant safety risks were identified in any of these studies.
In studies conducted following oral administration, dapoxetine was not carcinogenic in rats when administered daily for approximately two years at doses up to 225 mg / kg / day.die, producing nearly double exposure (AUC) to that seen in male patients given the maximum recommended human dose (Maximum Recommended Human Dose - MRHD) of 60 mg. Dapoxetine did not cause tumors even in rasH2 transgenic mice when administered at maximum possible doses of 100 mg / kg for 6 months and 200 mg / kg for 4 months. Steady-state exposures of dapoxetine in mice following oral administration for 6 months of doses of 100 mg / kg /diewere lower than the clinically observed exposures after a single 60 mg dose.
There were no effects on fertility, reproductive capacity or morphology of reproductive organs in male or female rats, nor adverse signs of embryotoxicity or foetotoxicity in rat or rabbit. Reproductive toxicity studies do not include those evaluating the risk of side effects after exposure during the peri and postnatal period.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Core of the tablet:
Lactose monohydrate
Microcrystalline cellulose
Croscarmellose sodium
Anhydrous colloidal silica
Magnesium stearate
Tablet coating:
Lactose monohydrate
Hypromellose
Titanium dioxide (E171)
Triacetin
Black iron oxide (E172)
Yellow iron oxide (E172)
06.2 Incompatibility
Not relevant.
06.3 Period of validity
3 years
06.4 Special precautions for storage
This medicine does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Child resistant PVC-PE-PVDC / aluminum blisters in packs of 1, 2, 3 or 6 film-coated tablets. Not all pack sizes may be marketed.
06.6 Instructions for use and handling
Medicines should not be disposed of via wastewater or household waste.Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
A. Menarini Industrie Farmaceutiche Riunite s.r.l.
Via Sette Santi, 3
50131 Florence
08.0 MARKETING AUTHORIZATION NUMBER
Priligy 30 mg film-coated tablets
1 tablet A.I.C. n. 039041052
Priligy 30 mg film-coated tablets
2 tablets A.I.C. n. 039041064
Priligy 30 mg film-coated tablets
3 tablets A.I.C. n. 039041013
Priligy 30 mg film-coated tablets
6 tablets A.I.C. n. 039041025
Priligy 60 mg film-coated tablets
1 tablet A.I.C. n. 039041076
Priligy 60 mg film-coated tablets
2 tablets A.I.C. n. 039041088
Priligy 60 mg film-coated tablets
3 tablets A.I.C. n. 039041037
Priligy 60 mg film-coated tablets
6 tablets A.I.C. n. 039041049
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
Date of first authorization: 15 May 2009
Date of last renewal: December 17, 2013
10.0 DATE OF REVISION OF THE TEXT
AIFA Resolution of November 2014
