Active ingredients: Fluoxetine
Prozac 20 mg dispersible tablets
Prozac package inserts are available for pack sizes:- Prozac 20 mg dispersible tablets
- Prozac 20 mg hard capsules
- Prozac 20 mg / 5 ml oral solution
Why is Prozac used? What is it for?
Prozac contains fluoxetine which belongs to a group of medicines called selective serotonin reuptake inhibitor (SSRI) antidepressants. This medicine is used to treat the following conditions:
Adults:
- Major depressive episodes
- Obsessive Compulsive Disorder
- Bulimia nervosa: Prozac is used in conjunction with psychotherapy for the reduction of binge eating and purging.
Children and adolescents aged 8 years and over:
- Moderate to severe major depressive disorder, if the depression does not respond to psychotherapy after 4-6 sessions. Prozac should only be offered to a child or young person with moderate to severe major depressive disorder in association with psychotherapy.
Contraindications When Prozac should not be used
Do not take Prozac if:
- You are allergic (hypersensitive) to fluoxetine or any of the other ingredients of Prozac (see section 6). If you get a skin rash or other allergic reactions (such as itching, swollen lips or face and shortness of breath), stop taking the tablets immediately and contact your doctor immediately.
- You are taking other medicines known as non-selective monoamine oxidase inhibitors or reversible monoamine oxidase type A inhibitors (MAOIs), as serious or even life-threatening reactions can occur. Examples of such MAOIs include medicines used to treat depression such as nialamide, iproniazid, moclobemide, phenelzine, tranylcypromine, isocarboxazid, toloxatone and also linezolid (an antibiotic) and methylthioninium chloride also called methylene blue (indicated for the acute symptomatic treatment of methemoglobinemia induced by drugs or chemical agents, for the local treatment of skin infections, such as plaque psoriasis, acne vulgaris and cold sores and as a diagnostic for renal function for the calculation of the glomerular filtration rate)
Prozac treatment should be started at least 2 weeks after stopping treatment with an irreversible MAOI (such as tranylcypromine).
However, Prozac treatment can be started the day after stopping treatment with some reversible MAOIs [such as moclobemide, linezolid, methylthioninium chloride (methylene blue)].
Do not take any MAOIs for at least 5 weeks after you stop taking Prozac. If you have been prescribed Prozac for a long time and / or in high doses, your doctor needs to keep in mind a longer time interval.
Take special care with Prozac Tell your doctor if any of the following apply to you:
- epilepsy or seizures. If you have a seizure (fits) or experience an increase in the frequency of seizures, contact your doctor immediately; you may need to stop taking Prozac;
- if you have or have had in the past episodes of mania; if you have an episode of mania, contact your doctor immediately as you may need to stop taking Prozac;
- diabetes (your doctor may need to adjust your insulin dose or other diabetes treatment);
- liver problems (your doctor may need to adjust your dose);
- heart problems;
- low heart rate at rest and / or if you are aware that you may have a salt deficiency as a result of severe and prolonged diarrhea and vomiting (feeling sick) or following the use of diuretics (urinating tablets);
- glaucoma (increased pressure inside the eye);
- ongoing treatment with diuretics (urinating tablets), especially if you are elderly;
- treatment with ECT (electroconvulsive therapy);
- history of bleeding disorders or bruising or unusual bleeding;
- ongoing treatment with medicines that improve blood flow (see "Taking other medicines");
- current treatment with tamoxifen (used to treat breast cancer) (see "Taking other medicines");
- begins to feel restless and cannot sit or stand still (akathisia). Increasing the dose of Prozac can make the situation worse;
- onset of fever, muscle stiffness or tremor, changes in mental status such as confusion, irritability and extreme agitation; you may be affected by the so-called "serotonin syndrome" or "neuroleptic malignant syndrome". Although this syndrome occurs rarely, it can give rise to potentially life-threatening conditions; contact your doctor immediately, as you may need to stop taking Prozac.
Thoughts of suicide and worsening of depression and anxiety disorder.
If you are depressed and / or have anxiety states you may sometimes have thoughts of harming or killing yourself. These thoughts may be increased when you first start treatment with antidepressants, as these medicines take a period of time to be effective, usually about 2 weeks but sometimes even longer.
You may be more likely to think like this:
- If you have previously had thoughts about killing or harming yourself.
- If you are a young adult. Data from clinical trials have shown an increased risk of suicidal behavior in adults aged less than 25 years with psychiatric disorders who were treated with an antidepressant.
If at any time you have thoughts of harming or killing yourself, contact your doctor or go to a hospital immediately. You may find it helpful to tell a relative or close friend that you are depressed or have an anxiety disorder, and ask them to read this leaflet. You may ask them to tell you if they think your depression or anxiety is getting worse, or if they are concerned about changes in his behavior.
Use in children and adolescents aged between 8 and 18 years
When taking this type of medicine, patients under 18 have an increased risk of side effects such as suicide attempt, suicidal thoughts and hostile attitude (especially aggressive, oppositional and anger behavior). Prozac should be used in children and adolescents aged 8 to 18 years only for the treatment of moderate to severe major depressive episodes (in combination with psychotherapy) and should not be used to treat other situations. Furthermore, only limited information is available in this age group regarding the long-term safety of Prozac on growth, puberty, mental, emotional and behavioral development. Despite this, and in patients under the age of 18, doctors may prescribe Prozac for the treatment of moderate to severe episodes of major depression in combination with psychotherapy if they feel this is the best solution for them. If your doctor has prescribed Prozac for a patient under 18 and you want clarification, please go back to your doctor. You should inform your doctor if any of the above symptoms appear or worsen while taking Prozac by patients under the age of 18. Prozac should not be used in the treatment of children under the age of 8.
Precautions for use What you need to know before taking Prozac
Pregnancy
Tell your doctor as soon as possible if you are or might be pregnant, or planning to become pregnant. In infants whose mothers took fluoxetine during the first months of pregnancy, there have been some studies that suggest an increased risk of birth defects affecting the heart. In the general population, approximately 1 in 100 newborns is born with a heart defect. This increased to about 2 in 100 newborns in mothers who took fluoxetine. Together with your doctor, you may decide to gradually stop taking Prozac during pregnancy. However, depending on the circumstances, your doctor may suggest that it is better for you to continue taking Prozac. When taken during pregnancy, especially in last 3 months of pregnancy, medicines such as Prozac may increase the risk of a serious condition in newborns called persistent pulmonary hypertension of the newborn (PPHN), which causes the newborn to breathe faster and have a bluish color. they occur during the first 24 hours after birth. If this happens to your newborn, contact your midwife and / or doctor immediately.Caution is recommended when taken during pregnancy, especially during the terminal period of pregnancy or just before delivery as the following effects have been reported in newborns: irritability, tremor, muscle weakness, persistent crying, difficulty in sucking or sleeping.
Breastfeeding
Fluoxetine is excreted in breast milk and can cause unwanted effects in babies. Breastfeeding should only be done if clearly necessary. If breastfeeding is continued, your doctor may prescribe a lower dose of fluoxetine.
Fertility
Fluoxetine, in animal studies, has been shown to reduce sperm quality. In theory, this could affect fertility, but the impact on human fertility has not yet been observed.
Driving and using machines
Prozac can impair judgment or coordination skills. Do not drive or use any tools or machines without the consent of your doctor or pharmacist.
Important information about some of the ingredients of Prozac
Prozac contains sorbitol. If you have been told by your doctor that you have an "intolerance to some sugars, contact your doctor before taking this medicinal product.
Interactions Which drugs or foods can change the effect of Prozac
Taking with other medicines
Tell your doctor or pharmacist if you are taking or have recently taken any other medicines (up to 5 weeks before), including those obtained without a prescription. Prozac can affect the way some other medicines work (interaction), especially the following:
- some monoamine oxidase inhibitors (MAOIs), some used to treat depression). Non-selective MAOIs and Type A MAOIs should not be used with Prozac as serious or even life-threatening reactions (serotonin syndrome) can occur (see section "Do not take Prozac"). Prozac treatment should be started strictly at least 2 weeks after stopping an irreversible MAOI (such as tranylcypromine). However, fluoxetine treatment can be started the next day after stopping some reversible MAOIs [such as moclobemide, linezolid, methylthioninium chloride (methylene blue)]. Some Type B MAOIs (selegiline) can be used with Prozac as long as your doctor will closely monitor you.
- lithium, tryptophan; when these medicines are taken with Prozac there is an increased risk of developing serotonin syndrome. Your doctor will check you more frequently.
- phenytoin (for epilepsy); as Prozac can affect the blood levels of this medicine, your doctor may need to administer phenytoin more carefully and monitor when given with Prozac.
- tramadol (a pain reliever) or triptans (for 'migraine); there is an increased risk of hypertension (increased blood pressure).
- medicines that can alter the heart rhythm, eg. class IA and III antiarrhythmics, antipsychotics (e.g. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antibacterial agents (e.g. sparfloxacin, moxifloxacin, erythromycin IV, pentamidine), treatment against malaria and in particular halofantrine antihistamines (astemizole, mizolastine).
- flecainide or encainide (for heart disorders), carbamazepine (for epilepsy), tricyclic antidepressants (for example imipramine, desipramine and amitriptyline); because Prozac can somehow change the blood levels of these medicines, your doctor may have need to lower their dosage when given with Prozac.
- tamoxifen (used to treat breast cancer), as Prozac may change the levels of this medicine in the blood and a decrease in the effect of tamoxifen cannot be ruled out, your doctor may need to consider other antidepressant treatments.
- warfarin, NSAIDs (non-steroidal anti-inflammatory drugs) or other medicines that can improve blood flow (including clozapine, used to treat some mental disorders, and aspirin); Prozac may change the effect of these medicines on the blood. If Prozac treatment is started or stopped while you are taking warfarin, your doctor will need to perform some checks.
- you should not start taking the herbal preparation containing St. John's wort (Hypericum perforatum) while being treated with Prozac as this can lead to increased side effects. If you are already taking St John's Wort when you start taking Prozac, stop taking St John's Wort and tell your doctor at your first visit afterwards.
Taking Prozac with food and drink
- You can take Prozac with or without meals, as you prefer.
- You should avoid drinking alcohol while you are taking this medicine.
Pregnancy, breastfeeding and fertility.
Ask your doctor or pharmacist for advice before taking any medicine
Dose, Method and Time of Administration How to use Prozac: Posology
Always take Prozac exactly as your doctor has told you. If in doubt, consult your doctor or pharmacist. The instructions are also on the package label. Do not take more tablets than your doctor has prescribed.
Swallow the tablets whole with a sip of water, or dissolved in half a glass of water to be swallowed immediately and completely. Do not chew the tablets.
Adults:
The usual dose is:
- Depression: The recommended dose is 1 tablet (20 mg) per day. If necessary, your doctor will review and adjust the dosage within 3-4 weeks of starting treatment. If required, the dosage can be gradually increased to a maximum of 3 tablets (60 mg) per day. The dose should be increased with caution to make sure you get the lowest effective dose. You may not feel immediate improvement when you start treatment with your depression medicine. This is normal as an improvement in symptoms of depression may only occur after the first few weeks of therapy. Patients with depression should be treated for a period of at least 6 months.
- Bulimia nervosa: The recommended dose is 3 tablets (60 mg) per day.
- Obsessive Compulsive Disorder: The recommended dose is 1 tablet (20 mg) per day. If necessary, your doctor will review and adjust your dosage after 2 weeks of therapy. If required, the dosage can be gradually increased to a maximum of 3 tablets (60 mg) per day. If no improvement is seen within the first 10 weeks, your doctor will reevaluate your treatment.
Children and adolescents aged 8 to 18 with depression:
Treatment must be initiated and supervised by a specialist. The starting dose is 10 mg per day (given as 2.5 ml of Prozac oral solution). After 1-2 weeks, the doctor may increase the dose to 20 mg per day. The dose should be increased cautiously to make sure you are receiving the lowest effective dose. Children with low body weight may need lower doses. If there is a satisfactory response to treatment, the doctor will re-evaluate the need to continue treatment beyond 6 months. If there has been no improvement within the first 9 weeks, your doctor will need to reconsider your treatment.
Senior citizens:
Your doctor will take more caution in increasing the dose and the daily dosage should generally not exceed 2 tablets (40 mg). The maximum dose is 3 tablets (60 mg) per day.
Hepatic impairment:
If you have a liver disorder or are taking another medicine that may interfere with Prozac, your doctor may decide to prescribe a lower dose or advise you to take Prozac every other day.
Overdose What to do if you have taken too much Prozac
- If you take too many tablets, go to the nearest hospital emergency department or tell your doctor right away.
- If possible, take your Prozac pack with you.
Symptoms of overdose include: nausea, vomiting, seizures, heart disturbances (such as "irregular heartbeat and" cardiac arrest), breathing disturbances and changes in mental status ranging from agitation to coma.
If you forget to take Prozac
- If you forget to take a dose, don't worry. Take your next dose at the usual time the following day. Do not take a double dose to make up for a forgotten dose.
- Taking the medicine at the same time each day can help you remember to take it regularly.
If you stop taking Prozac
- Don't stop taking Prozac without asking your doctor first, even when you start to feel better. It is important that you take your medicine continuously.
- Make sure you don't run out of tablets.
When you stop taking Prozac you may notice the following effects (withdrawal effects): dizziness; tingling like feelings of pricks from pins and needles; sleep disturbances (realistic dreams, nightmares, inability to fall asleep); feeling restless or agitated; unusual tiredness or weakness; feeling anxious; nausea / vomiting; tremor; headache. Most people report that any symptoms that occur when they stop taking Prozac are mild and disappear within a few weeks. If you notice symptoms when stopping treatment, please contact your doctor. When you stop taking Prozac, your doctor will help you reduce your dose gradually over a week or two - this should help reduce the possibility of withdrawal effects. If you have any further questions on the use of Prozac, ask your doctor or pharmacist.
Side Effects What are the side effects of Prozac
Like all medicines, Prozac can cause side effects, although not everybody gets them.
- If at any time you have thoughts of harming or killing yourself, contact your doctor or go to a hospital immediately (see section 2).
- If you experience a rash or allergic reaction such as itching, swelling of the lips or tongue, difficulty in breathing, wheezing, stop taking the tablets immediately and tell your doctor immediately.
- If you feel restless and cannot sit or stand still, you may have a disorder called akathisia; an increase in your Prozac dose could make you feel worse. If you experience these sensations, contact your doctor.
- Tell your doctor immediately if your skin starts to redden or if you develop a different skin reaction or if your skin begins to blister or peel. This occurrence is very rare.
Some patients presented:
- a set of symptoms (known as "serotonin syndrome") including unexplained fever with rapid breathing and heart rate, sweating, muscle stiffness or tremors, confusion, extreme agitation or sleepiness (only rarely);
- feeling weak, drowsy or confused especially in older people and in people (elderly) who are taking diuretics (urinating tablets);
- prolonged and painful erection;
- irritability and extreme agitation;
- heart problems, such as fast or irregular heart rate, fainting, collapse or dizziness on standing which may indicate abnormal heart rate functioning.
If you get any of the side effects listed above, please tell your doctor immediately.
The following side effects have also been reported in patients taking Prozac:
Very common (may affect more than 1 in 10 patients)
- insomnia
- headache
- diarrhea, feeling of disgust (nausea)
- fatigue
Common (affects 1 to 10 users in 100)
- lack of appetite, weight loss
- nervousness, anxiety
- restlessness, poor concentration
- feeling tense
- reduced sexual desire and sexual problems (including difficulty in maintaining an "erection for sexual activity)
- sleep problems, unusual dreams, tiredness or sleepiness
- dizziness
- change in taste
- uncontrolled movements
- blurred vision
- feeling of fast and irregular heartbeat
- redness
- yawn
- indigestion, vomiting
- dry mouth
- rash, hives, itching
- excessive sweating
- joint pain
- urinalysis more frequently
- unexplained vaginal bleeding
- feeling of being unable to stand or shivering
Uncommon (affects 1 to 10 users in 1,000)
- feeling of detachment from oneself
- strange thoughts
- excessively high mood
- orgasm problems
- teeth grinding
- muscle twitching, involuntary movements, or problems with balance or coordination
- enlarged (dilated) pupils
- low blood pressure
- wheezing
- difficulty swallowing
- hair loss
- increased tendency to bruise
- cold sweats
- difficulty in passing urine
- feeling hot or cold
Rare (affects 1 to 10 users in 10,000)
- reduced levels of sodium in the blood
- uncontrolled non-habitual behavior
- hallucinations
- agitation
- panic attacks
- seizures
- vasculitis (inflammation of a blood vessel)
- rapid swelling of the tissues around the neck, face, mouth and / or throat
- pain in the tube that allows food and water to pass through the stomach
- sensitivity to sunlight
- breast milk secretion
Other (frequency cannot be estimated from the available data)
- thoughts of suicide or harming yourself
- reduced memory
- lung problems
- hepatitis, abnormal liver function tests
- muscular pain
- problems urinating
- confusional state
- stuttering
- nosebleeds
- ringing in the ears
- unexplained bruising or bleeding
Bone fractures - an increased risk of bone fractures has been observed in patients taking this type of medicine. If you have any of the symptoms listed and they are bothering you, or last for a certain period of time, please tell your doctor or pharmacist. Most of these side effects are likely to disappear with continued treatment.
Children and adolescents (8-18 years)
In addition to the possible side effects listed above, Prozac can slow growth and possibly delay sexual maturation. Nosebleeds have also been commonly reported in children. Very rare (may affect less than 1 in 10,000 patients) decrease in blood platelets, which increases the risk of bleeding or bruising
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
Expiry and Retention
Keep Prozac out of the reach and sight of children.
Do not use Prozac after the expiry date (EXP) which is stated on the package label. The expiry date refers to the last day of the month.
Do not store the tablets above 30 ° C.
If you have any other questions, ask your doctor or pharmacist.
Medicines should not be disposed of 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
What Prozac dispersible tablets contain
The active ingredient is fluoxetine hydrochloride. Each tablet contains fluoxetine hydrochloride equivalent to 20 milligrams (mg) of fluoxetine.
The other ingredients are: microcrystalline cellulose, sodium saccharin, mannitol, sorbitol, anise flavoring, peppermint flavoring, colloidal anhydrous silica, pregelatinised maize starch, sodium stearyl fumarate and crospovidone.
What Prozac dispersible tablets look like and contents of the pack
The tablets are white, elongated, uncoated and pre-scored. The tablets can be divided into equal halves. The tablets are available in blisters of 14, 20, 28, 30, 50, 56, 70 or 100 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
PROZAC
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each dispersible tablet contains:
active ingredient: 22.36 mg of fluoxetine hydrochloride equivalent to 20.00 mg of fluoxetine.
For excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Dispersible tablet.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Major depressive episodes.
Obsessive Compulsive Disorder.
Bulimia nervosa: PROZAC dispersible tablets are indicated in association with psychotherapy for the reduction of binge eating and purging activity.
04.2 Posology and method of administration
For oral administration in adults only.
Major Depressive Episodes:
Adults and the elderly: 20 mg / day to 60 mg / day. As an initial dose, 20 mg / day is recommended. Although there may be a greater potential for undesirable effects at higher doses, a dose increase may be considered after three weeks in the absence of a therapeutic response.
According to WHO consensus statement, antidepressant treatment should continue for at least 6 months.
Obsessive Compulsive Disorder:
Adults and the elderly: 20 mg / day to 60 mg / day. As an initial dose, 20 mg per day is recommended. Although there may be a greater potential for undesirable effects at higher doses, a dose increase may be considered after two weeks in the absence of a therapeutic response.
If no improvement is observed within 10 weeks, fluoxetine treatment should be resumed. If a good therapeutic response has been achieved, treatment can be continued at an individually adjusted dosage. Although there are no systematic studies to establish how long to continue fluoxetine treatment, OCD is a chronic condition and it is reasonable to consider prolonging therapy beyond 10 weeks in responding patients. Variations in dosage should be made carefully on each individual to keep the patient at the lowest effective dose. The need for treatment should be reassessed periodically. In patients who have responded well to pharmacotherapy, some clinicians find simultaneous behavioral psychotherapy useful.
Long-term efficacy (beyond 24 weeks) has not been demonstrated in OCD.
Bulimia nervosa:
Adults and the elderly: a dose of 60 mg / day is recommended.
Long-term efficacy (beyond 3 months) has not been demonstrated in bulimia nervosa.
In all indications:
The recommended dose can be increased or decreased. Doses above 80 mg / day have not been systematically evaluated.
Fluoxetine can be administered in single or divided doses, with or without meals.
When dosing is stopped, the pharmacologically active substances will persist in the body for weeks. This should be borne in mind when starting or stopping treatment. In most patients, a gradual reduction in dosage is not necessary.
Intake by children and adolescents under the age of 18:
PROZAC dispersible tablets should not be used for the treatment of children and adolescents under 18 years of age.
Elderly: Caution is advised when increasing the dose and the daily dose should generally not exceed 40 mg. The maximum recommended dose is 60 mg / day.
A lower or less frequent dose (eg 20 mg every other day) should be considered in patients with hepatic insufficiency (see section 5.2), or in patients in whom there is the possibility of an "interaction between PROZAC dispersible tablets. and medicinal products taken concomitantly (see section 4.5).
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Monoamine Oxidase InhibitorsCases of serious and sometimes fatal reactions have been reported in patients taking an SSRI in combination with a monoamine oxidase inhibitor (MAOI), and in patients who had recently stopped treatment with an SSRI and started that with a MAOI. Fluoxetine treatment should only be started 2 weeks after stopping an irreversible MAOI.
Some cases have presented with features similar to serotonin syndrome (which may resemble and be diagnosed as neuroleptic malignant syndrome). Cyproheptadine or dantrolene may be of benefit to patients with such reactions. Symptoms of a drug interaction with a MAOI include: hyperthermia, rigidity, myoclonus, autonomic nervous system instability with possible rapid fluctuations in vital signs, mental status changes including confusion, irritability and extreme agitation leading to delirium and coma.
Therefore, fluoxetine is contraindicated in combination with a non-selective MAOI. Likewise, at least 5 weeks should elapse after discontinuing fluoxetine treatment before initiating therapy with a MAOI. If fluoxetine is prescribed for a long time and / or at high doses, a time interval should be considered. longer.
The combination is not recommended. Fluoxetine treatment can be started the day after discontinuation of a reversible MAOI (eg moclobemide).
04.4 Special warnings and appropriate precautions for use
Warnings
Skin rash and allergic reactions: Rash, anaphylactoid events and progressive systemic events, sometimes serious (involving skin, kidney, liver or lung) have been reported. Upon the appearance of skin rash or other allergic phenomena for which a different etiology cannot be identified, the administration of fluoxetine must be suspended.
For use by children and adolescents under the age of 18:
PROZAC dispersible tablets should not be used for the treatment of children and adolescents under 18 years of age. Suicidal behaviors (suicide attempts and suicidal ideation) and hostility (essentially aggression, oppositional behavior and anger) were observed more frequently in clinical trials in children and adolescents treated with antidepressants than in those treated with placebo. If, based on medical need, a decision to treat is made, the patient should be closely monitored for the appearance of suicidal symptoms. Furthermore, long-term safety data for children and adolescents are not available with regard to growth, maturation and cognitive and behavioral development.
Precautions:
Convulsions: Seizures pose a potential risk with antidepressant medications. Therefore, as with other antidepressants, fluoxetine should be administered with caution to patients with a history of seizures. Treatment should be discontinued in any patient who experiences seizures or in whom an increase in seizure frequency is observed. Administration of fluoxetine should be avoided in patients with unstable seizure disorders / epilepsy and patients with controlled epilepsy should be carefully monitored.
Mania: Antidepressants should be used with caution in patients with a history of mania / hypomania. As with all antidepressant drugs, fluoxetine should be discontinued in any patient entering a manic phase.
Hepatic / Renal Function: Fluoxetine is extensively metabolised by the liver and eliminated by the kidneys. In patients with significant hepatic dysfunction, a lower dose is recommended, e.g. an alternate day dosage. When fluoxetine 20 mg / day was administered for 2 months, patients with severe renal impairment (GFR dialysis showed no difference in plasma levels of fluoxetine or norfluoxetine compared to control subjects with normal renal function.
Heart disease: None of the conduction alterations leading to cardiac arrest were observed on ECG in 312 patients who received fluoxetine in double-blind clinical trials. However, clinical experience in acute heart disease is limited, so caution is advised.
Weight lossWeight loss may occur in patients taking fluoxetine, but this is usually proportional to the starting body weight.
Diabetes: In diabetic patients, treatment with an SSRI can impair glycemic control. Hypoglycaemia occurred during fluoxetine therapy, while hyperglycaemia developed after drug discontinuation. Dosage adjustment of the insulin and / or oral hypoglycemic agent may be required.
Suicide: As improvement may not occur during the first few weeks of treatment, as with all antidepressants, patients should be closely monitored during this period. The possibility of a suicide attempt is inherent in depression and may persist until significant remission of this disease occurs. It is general clinical experience with all therapies for depression that the risk of suicide may increase in the early stages of improvement.
Hemorrhage: There have been reports of cutaneous bleeding manifestations such as ecchymosis and purpura with the use of SSRIs. Ecchymosis has been reported as an infrequent event during treatment with fluoxetine. Other haemorrhagic manifestations (eg gynecological haemorrhages, gastrointestinal bleeding and other cutaneous or mucosal bleeding) have been reported rarely. In patients who taking SSRIs, caution is advised, especially during concomitant use with oral anticoagulants, drugs known to affect platelet function (eg atypical antipsychotics such as clozapine, phenothiazines, most tricyclic antidepressants, aspirin, NSAIDs ) or other drugs that may increase the risk of bleeding, as well as in patients with a history of pathological manifestations characterized by bleeding.
Electroconvulsive therapy (ECT): In fluoxetine-treated patients receiving ECT treatment, there have been rare reports of prolonged seizures, so caution is advised.
St. John's wort: When selective serotonin reuptake inhibitors and herbal preparations containing St. John's wort (Hypericum perforatum) are used together, increased serotonergic-type effects, such as serotonin syndrome, may occur.
On rare occasions, the development of a serotonin syndrome or neuroleptic malignant syndrome-like events have been reported in association with fluoxetine treatment, particularly when fluoxetine is administered in combination with other serotonergic drugs (among others L-tryptophan) and / or neuroleptics. Since these syndromes can give rise to potentially life-threatening conditions for the patient, if such events occur (characterized by groupings of symptoms such as hyperthermia, rigidity, myoclonus, autonomic nervous system instability with possible rapid fluctuations of vital signs, changes in the state including confusion, irritability and extreme agitation up to delirium and coma) fluoxetine treatment should be discontinued and symptomatic supportive treatment initiated.
04.5 Interactions with other medicinal products and other forms of interaction
Half-life: The long elimination half-lives of both fluoxetine and norfluoxetine (see section 5.2) should be borne in mind when considering pharmacodynamic or pharmacokinetic drug interactions (e.g. when switching from fluoxetine to other antidepressants).
Monoamine Oxidase Inhibitors: (see section 4.3).
Combinations not recommended:
MAOI-Type A (see section 4.3)
Associations requiring precautions for their use:
MAOI-Type B (selegiline): risk of serotonin syndrome. Clinical monitoring is recommended.
Phenytoin: Alterations in blood levels have been observed when combined with fluoxetine. In some cases, manifestations of toxicity have occurred. It is therefore advisable to administer the concomitant drug according to conservative therapeutic schemes and to carefully follow the patient's clinical conditions.
Serotonergic drugs: Co-administration with serotonergic drugs (eg tramadol, triptans) may increase the risk of developing a serotonin syndrome. The association with triptans adds an additional risk of coronary vasoconstriction and hypertension.
Lithium and tryptophan: There have been reports of serotonin syndrome when SSRIs have been administered in combination with lithium or tryptophan and, therefore, the concomitant use of fluoxetine with these drugs should be done with caution. When fluoxetine is given in combination with lithium, more targeted and frequent clinical monitoring is required.
CYP2D6 isoenzyme: Since the metabolism of fluoxetine (as for tricyclic antidepressants and other selective antidepressants for serotonin) affects the CYP2D6 isoenzymatic system in the liver, concomitant therapy with drugs equally metabolised by this enzyme system may lead to drug interactions. Concomitant therapy with drugs predominantly metabolised by this isoenzyme, and which have a limited therapeutic index (such as flecainide, encainide, carbamazepine and tricyclic antidepressants), should be initiated or adjusted from the lowest value of the dose range. This will need to be done even if fluoxetine was taken within the previous 5 weeks.
Oral anticoagulantsAltered anticoagulant effects (laboratory data and / or clinical symptoms and signs), which do not fit into a homogeneous category, but include increased bleeding, have been observed infrequently following co-administration of fluoxetine and oral anticoagulants.
When fluoxetine therapy is initiated or discontinued in patients receiving warfarin, close monitoring of coagulation should be performed (see section 4.4, Hemorrhage).
Electroconvulsive therapy (ECT): In fluoxetine-treated patients receiving ECT treatment, there have been rare reports of prolonged seizures, so caution is advised.
Alcohol: In routine testing, fluoxetine does not cause an increase in blood alcohol levels or potentiate the effects of alcohol. However, the combination of SSRI and alcohol treatment is not recommended.
St. John's wort: As with other SSRIs, pharmacodynamic interactions may occur between fluoxetine and the herbal preparation containing St. John's wort (Hypericum perforatum), which can lead to increased side effects.
04.6 Pregnancy and lactation
Pregnancy: Data collected from a large number of pregnancies do not indicate that fluoxetine has a teratogenic effect. Fluoxetine can be used during pregnancy, although caution should be used, especially in late pregnancy or just before the onset of labor as the following effects have been reported in newborns: irritability, tremor, hypotonia, persistent crying, difficulty sucking or sleeping. These symptoms may indicate both serotonergic effects and a withdrawal syndrome. The time of onset and duration of these symptoms may be related to the long half-life of fluoxetine (4-6 days) and its active metabolite, norfluoxetine (4-16 days).
Feeding time: Fluoxetine and its active metabolite norfluoxetine are known to be excreted in human breast milk. Adverse events have been reported in breastfed infants. If treatment with fluoxetine is deemed necessary, discontinuation of breastfeeding should be considered; however, if breastfeeding is continued, the lowest effective dose of fluoxetine should be prescribed.
04.7 Effects on ability to drive and use machines
Although fluoxetine has been shown not to interfere with psychomotor performance in healthy volunteers, any psychoactive drug can impair judgment or professional skills. Patients should be advised to avoid driving a vehicle or operating hazardous machinery until they are reasonably aware that their performance is not impaired.
04.8 Undesirable effects
Undesirable effects may decrease in intensity and frequency with continued treatment and generally do not lead to discontinuation of therapy.
As with other SSRIs, the following side effects have been observed:
Body as a whole: Manifestations of hypersensitivity (e.g. pruritus, rash, urticaria, anaphylactoid reaction, vasculitis, serum sickness-like reaction, angioedema) (see sections 4.3 and 4.4), tremors, serotonin syndrome, photosensitivity, very rarely toxic epidermal necrolysis (Lyell's syndrome).
Digestive system: Gastrointestinal disturbances (e.g. diarrhea, nausea, vomiting, dyspepsia, dysphagia, altered taste), dry mouth. Abnormal liver function tests have been reported rarely. Very rare cases of idiosyncratic hepatitis.
Nervous system: Headache, sleep disturbances (e.g. abnormal dreams, insomnia), dizziness, anorexia, fatigue (e.g. somnolence, drowsiness), euphoria, transient abnormal movements (e.g.nervous tics, ataxia, tremor, myoclonus), convulsions and psychomotor agitation. Hallucinations, manic reaction, confusion, agitation, anxiety and associated symptoms (e.g. nervousness), disturbances in concentration and cognition (e.g. depersonalization), panic attacks (these symptoms may be due to an underlying disease), very rarely serotonin syndrome.
Urogenital system: Urinary retention and altered urinary frequency.
Disorders of reproduction: Sexual dysfunction (delayed or absent ejaculation, anorgasmia), priapism, galactorrhea.
Miscellaneous: Alopecia, yawning, vision abnormalities (e.g. blurred vision, mydriasis), sweating, vasodilation, arthralgia, myalgia, postural hypotension, ecchymosis. Other haemorrhagic manifestations (e.g. gynecological haemorrhages, gastrointestinal bleeding and other cutaneous or mucosal bleeding) have been reported rarely (see section 4.4, Hemorrhage).
Hyponatremia. Hyponatremia (including sodium values below 110 mmol / l) has been reported rarely and was found to be reversible with fluoxetine suspension. Some cases were probably due to the syndrome of inappropriate antidiuretic hormone secretion. Most of the reports were found in older patients, and in patients treated with diuretics or with reduced blood volume for any other reason.
Respiratory System: Pharyngitis, dyspnoea. Pulmonary events (including inflammatory processes of variable histopathology and / or fibrosis) have been reported rarely. Dyspnea may be the only warning symptom.
Discontinuation symptoms have been reported following discontinuation of treatment with SSRIs, although current evidence does not seem to indicate this is due to an addiction problem. Common symptoms include dizziness, paraesthesia, headache, anxiety, and nausea, most of which are mild and self-limiting. Fluoxetine has only rarely been associated with these symptoms. a gradual reduction in dosage.
04.9 Overdose
Cases of overdose due to fluoxetine alone generally have a mild course. Symptoms of overdose include nausea, vomiting, convulsions, cardiovascular dysfunction ranging from asymptomatic arrhythmia to cardiac arrest, pulmonary dysfunction and signs of an altered CNS condition ranging from excitement to coma.
Fatal outcome attributed to fluoxetine overdose alone has been extremely rare.
It is advisable to monitor cardiac function and vital signs, as well as general symptomatic and supportive measures. No specific antidotes are known.
Forced diuresis, dialysis, haemoperfusion and replacement transfusion are unlikely to offer benefits. Activated charcoal, which can be used in combination with sorbitol, may be an even more effective treatment than emesis or gastric lavage. When treating an overdose, consider the possibility of multiple drug involvement. In patients who have taken excessive amounts of a tricyclic antidepressant, a longer period of time for close medical observation may be required if they are also taking, or have recently taken, fluoxetine.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antidepressants; Selective serotonin reuptake inhibitors.
ATC code: N06AB03
Fluoxetine is a selective serotonin reuptake inhibitor, and this probably accounts for the mechanism of action. Fluoxetine has virtually no affinity for other receptors such as alpha1-, alpha2- and beta-adrenergics; serotonergics; dopaminergics type 1 histamine receptors; muscarinics and GABA receptors.
Major Depressive Episodes: Clinical trials comparing placebo and active substances were performed in patients with major depressive episodes. PROZAC was shown to be significantly more effective than placebo, as shown by the Hamilton Depression Rating Scale (HAM-D). Compared to placebo, PROZAC resulted in significantly higher rates of response (defined by a 50% reduction in HAM-D score) and remission in these studies.
Obsessive Compulsive Disorder: In short-term clinical trials (lasting less than 24 weeks), fluoxetine was shown to be significantly more effective than placebo. The therapeutic effect was observed at 20 mg / day, but higher doses (40 or 60 mg / day) demonstrated a higher response rate. In long-term clinical trials (three short-term clinical trials with extension phase and a relapse prevention study) efficacy has not been demonstrated.
Bulimia nervosa: In short-term clinical studies (less than 16 weeks duration), in outpatients who fully met the DSM-III-R criteria for bulimia nervosa, fluoxetine 60 mg / day was shown to be significantly more efficacy of placebo in reducing binge eating and purging. However, as far as long-term effectiveness is concerned, it is not possible to draw a conclusion.
Two placebo-controlled clinical trials were conducted in patients who met the diagnostic criteria for Pre-Menstrual Dysphoric Disorder as reported on the DSM-IV. Patients were included if they had symptoms of sufficient severity to interfere with their occupational and social function and in their relationship life with others. Patients using oral contraceptives were excluded. In the first study with a continuous dose of 20 mg / day for 6 menstrual cycles, improvement was observed in the primary efficacy parameter (irritability, anxiety and dysphoria). In the second study, with intermittent dosing during the luteal phase (20 mg / day for 14 days) for 3 menstrual cycles, improvement was observed in the primary efficacy parameter (score based on the daily recording scale of the severity of the disorders, Daily Record of Severity of Problems score). However, no definitive conclusions on the efficacy and duration of treatment can be drawn from these studies.
05.2 Pharmacokinetic properties
Absorption
After oral administration, fluoxetine is well absorbed from the gastrointestinal tract. Bioavailability is not affected by food intake.
Distribution
Fluoxetine is extensively bound to plasma proteins (approximately 95%) and is distributed diffusely in the body (Volume of distribution: 20-40 l / kg). Equilibrium plasma concentrations are reached only after several weeks of treatment. The equilibrium concentrations after prolonged dosing are similar to those observed after 4-5 weeks.
Metabolism
Fluoxetine has a non-linear pharmacokinetic profile with a hepatic first pass effect. The maximum plasma concentration is generally reached 6 to 8 hours after administration. Fluoxetine is extensively metabolised by the polymorphic enzyme CYP2D6. Fluoxetine is predominantly metabolised by the liver to the active metabolite norfluoxetine (demethylfluoxetine) via demethylation.
Elimination
The elimination half-life of fluoxetine is 4-6 days, while that of norfluoxetine is 4-16 days. These long half-lives are responsible for the persistence of the drug for 5-6 weeks after its discontinuation. Elimination occurs mainly by renal route (about 60%). Fluoxetine is excreted in breast milk.
Populations at risk
Senior citizens:
Kinetic parameters are not altered in healthy elderly compared to younger subjects.
Liver failure:
In case of liver failure (alcoholic cirrhosis), the half-lives of fluoxetine and norfluoxetine are increased to 7 and 12 days, respectively. A lower or less frequent dose should be considered.
Kidney failure:
After administration of a single dose of fluoxetine in patients with mild, moderate or complete (anuria) renal insufficiency, the kinetic parameters were not altered compared to healthy volunteers. However, after repeated administration, an increase in the equilibrium plateau of plasma concentrations may be observed.
05.3 Preclinical safety data
Studies conducted in vitro or on animals they did not show a carcinogenic, mutagenic effect or insufficient fertility.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
PROZAC 20 mg dispersible tablets: each dispersible tablet contains: microcrystalline cellulose, sodium saccharin, mannitol, sorbitol, anise flavor, peppermint flavor, colloidal anhydrous silica, fluid starch, sodium stearyl fumarate, povidone.
06.2 Incompatibility
Don't report.
06.3 Period of validity
PROZAC 20 mg dispersible tablets: 2 years.
(with intact packaging)
06.4 Special precautions for storage
Store at controlled room temperature (15-30 ° C).
06.5 Nature of the immediate packaging and contents of the package
PROZAC 20 mg dispersible tablets
The product is packaged in blisters consisting of ACLAR and aluminum.
Blister of 12 dispersible tablets.
Blister packs of 28 dispersible tablets.
06.6 Instructions for use and handling
PROZAC 20 mg dispersible tablets:
Swallow without chewing or dissolve the tablet in water, diluting to taste.
07.0 MARKETING AUTHORIZATION HOLDER
ELI LILLY ITALIA S.p.A.
Via Gramsci, 731/733
50019 Sesto Fiorentino (FI)
08.0 MARKETING AUTHORIZATION NUMBER
PROZAC 20 mg dispersible tablets (12 tablets): AIC N. 025970031
PROZAC 20 mg dispersible tablets (28 tablets): AIC N. 025970056
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
PROZAC 20 mg dispersible tablets (12 tablets): 01 April 2003
PROZAC 20 mg dispersible tablets (28 tablets): 01 April 2003
10.0 DATE OF REVISION OF THE TEXT
23/03/2007
