10 or 20mg Fluoxetine (as Fluoxetine hydrochloride)
Mechanism of action: Fluoxetine is a selective inhibitor of serotonin reuptake, and has practically no affinity to other receptors.
Absorption: Fluoxetine is well absorbed from the gastro-intestinal tract after oral administration with oral bioavailability estimated to be at least 60-80%. The bioavailability is not affected by food intake.
Distribution: Fluoxetine is extensively bound to plasma proteins (about 95%) and it is widely distributed (volume of distribution: 20-40 L/kg). Steady-state plasma concentrations are achieved after dosing for several weeks.
Excretion: The elimination half-life of fluoxetine is 4 to 6 days and for norfluoxetine 4 to 16 days. Excretion is mainly (about 60%) via the kidney. Fluoxetine is secreted into breast milk.
Metabolism: Maximum plasma concentration is generally achieved 6 to 8 hours after administration. Fluoxetine is primarily metabolised by the liver to the active metabolite norfluoxetine.
1- Major depressive episodes.
2- Obsessive-compulsive disorder.
3- Bulimia nervosa: Fluoxetine is indicated as a complement of psychotherapy for the reduction of binge-eating and purging activity.
Children and Adolescents Aged 8 Years and Above:
Moderate to severe major depressive episode, if depression is unresponsive to psychological therapy after 4-6 sessions, antidepressant medication should be offered to a child or young person with moderate to severe depression only in combination with a concurrent psychological therapy.
Hypersensitivity to the active substance or to any of the excipients.
Fluoxetine is contra-indicated in combination with irreversible, non-selective monoamine oxidase inhibitors (e.g. iproniazid) .
Fluoxetine is contra-indicated in combination with metoprolol used in cardiac failure.
Special warnings and precautions:
- Suicide-related behaviours and hostility were more frequently observed in clinical trials among children and adolescents (under 18 years)treated with antidepressants. Fluoxetine should only be used in children and adolescents aged 8 to 18 years for the treatment of moderate to severe major depressive episodes and it should not be used in other Indications.
- Depression is associated with an increased risk of suicidal thoughts and self-harm. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs.
- Fluoxetine should be used with caution in patients with conditions such as congenital long QT syndrome, a family history of QT prolongation or other clinical conditions that predispose to arrhythmias. If patients with stable cardiac disease are treated, an ECG review should be considered before treatment is started.
- On rare occasions development of a serotonin syndrome or neuroleptic malignant syndrome-like events have been reported in association with treatment of fluoxetine. As these syndromes may result in potentially life-threatening conditions, treatment with fluoxetine should be discontinued if such events occur and supportive symptomatic treatment should be initiated.
- Antidepressants should be used with caution in patients with a history of mania. As with all antidepressants, fluoxetine should be discontinued in any patient entering a manic phase.
- Seizures are a potential risk with antidepressant drugs. Therefore, as with other antidepressants, fluoxetine should be introduced cautiously in patients who have a history of seizures. Treatment should be discontinued in any patient who develops seizures or where there is an increase in seizure frequency
- There have been rare reports of prolonged seizures in patients on fluoxetine receiving ECT treatment, therefore caution is advisable.
- In patients with diabetes, treatment with an SSRI may alter glycaemic control. Hypoglycaemia has occurred during therapy with fluoxetine and hyperglycaemia has developed following discontinuation. Insulin and/or oral hypoglycaemic dosage may need to be adjusted.
- Weight loss may occur in patients taking fluoxetine, but it is usually proportional to baseline body weight.
- Mydriasis has been reported in association with fluoxetine; therefore, caution should be used when prescribing fluoxetine in patients with raised intraocular pressure or those at risk of acute narrow-angle glaucoma.
- Fluoxetine, a potent inhibitor of CYP2D6, may lead to reduced concentrations of endoxifen, one of the most important active metabolites of tamoxifen. Therefore, fluoxetine should whenever possible be avoided during tamoxifen treatment.
- The use of fluoxetine has been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.
- Rash, anaphylactoid events and progressive systemic events, sometimes serious (involving skin, kidney, liver or lung), have been reported. Upon the appearance of rash or of other allergic phenomena for which an alternative aetiology cannot be identified, fluoxetine should be discontinued.
- Withdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt.
The risk of withdrawal symptoms may be dependent on several factors, including the duration and dose of therapy and the rate of dose reduction. Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), asthenia, agitation or anxiety, nausea and/or vomiting, tremor, and headache are the most commonly reported reactions.
- Selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction.
Effects on ability to drive and use machines:
Although fluoxetine has been shown not to affect psychomotor performance in healthy volunteers, any psychoactive drug may impair judgement or skills.
Patients should be advised to avoid driving a car or operating hazardous machinery until they are reasonably certain that their performance is not affected.
Pregnancy & Lactation:
Fluoxetine should not be used during pregnancy unless the clinical condition of the woman requires treatment with fluoxetine and justifies the potential risk to the foetus.
Fluoxetine and its metabolite norfluoxetine, are known to be excreted in human breast milk, therefor using during breast feeding is not recommended.
Side effects :
- Very common: insomnia, headache, diarrhoea, nausea, fatigue.
- common: anxiety, nervousness, restlessness, tension, libido decreased, sleep disorder and abnormal dreams, disturbance in attention, lethargy,somnolence, tremor,vision blurred,palpitations, vomiting, dry mouth, rash, urticaria, pruritus, hyperhidrosis, arthralgia, frequent urination, and weight decreased and gynaecological bleeding.
- Uncommon: Depersonalization, elevated mood, euphoric mood, thinking abnormal, orgasm abnormal, bruxism, suicidal thoughts and behavior, psychomotor hyperactivity, dyskinesia, ataxia, balance disorder, myoclonus, memory impairment, mydriasis, tinnitus, hypotension, dyspnoea, epistaxis, dysphagia, gastrointestinal haemorrhage, alopecia, increased tendency to bruise, cold sweat, muscle twitching, dysuria, sexual dysfunction, malaise, feeling abnormal, feeling cold, feeling hot, abnormal liver function tests
1- Contra-indicated combinations:
- Irreversible, non-selective monoamine oxidase inhibitors (e.g.iproniazid): Some cases of serious and sometimes fatal reactions have been reported in combination with fluoxetine.
- Metoprolol used in cardiac failure: risk of metoprolol adverse events, including excessive bradycardia, may be increased because of an inhibition of its metabolism by fluoxetine.
2- Not recommended combinations:
- Tamoxifen: Reduced efficacy of tamoxifen has been reported with concomitant usage of some SSRI antidepressants (e.g fluoxetine).
- Alcohol: fluoxetine did not raise blood alcohol levels or enhance the effects of alcohol. However, the combination of SSRI treatment and alcohol is not advisable.
- Mequitazine: risk of mequitazine adverse events may be increased because of an inhibition of its metabolism by fluoxetine.
- MAOI-A including linezolid and methylthioninium chloride: Risk of serotonin syndrome including diarrhoea, tachycardia, sweating, tremor, confusion or coma.
3- Combinations requiring caution:
- Phenytoin: Changes in blood levels have been observed when combined with fluoxetine. In some cases manifestations of toxicity have occurred.
- Serotoninergic drugs (lithium, tramadol, triptans): There have been reports of mild serotonin syndrome when SSRIs were given with drugs also having a serotoninergic effect.
- QT interval prolongation: co-administration of fluoxetine with medicinal products that prolong the QT interval, such as Class IA and III antiarrhythmics, antipsychotics (e.g. phenothiazine derivatives and haloperidol), tricyclic antidepressants, certain antimicrobial agents (e.g. sparfloxacin, moxifloxacin, erythromycin IV, pentamidine), anti-malaria treatment particularly halofantrine, certain antihistamines (astemizole, mizolastine), should be used with caution.
- Drugs affecting haemostasis (oral anticoagulants, whatever their mechanism, platelets antiaggregants including aspirin and NSAIDs): risk of increased bleeding.
- Cyproheptadine: There are individual case reports of reduced antidepressant activity of fluoxetine when used in combination with cyproheptadine.
- Drugs inducing hyponatremia: Hyponatremia is an undesirable effect of fluoxetine. Use in combination with other agents associated with hyponatremia (e.g. diuretics, desmopressin, carbamazepine and oxcarbazepine) may lead to an increased risk.
- Drugs lowering the epileptogenic threshold: Seizures are an undesirable effect of fluoxetine. Use in combination with other agents which may lower the seizure threshold may lead to an increased risk.
- Other drugs metabolised by CYP2D6: Fluoxetine is a strong inhibitor of CYP2D6 enzyme, therefore concomitant therapy with drugs also metabolised by this enzyme system may lead to drug interactions.
Dosage And Administration:
1- Major depressive episodes: The recommended dose is 20 mg daily.
Dosage should be reviewed and adjusted if necessary within 3 to 4 weeks of initiation of therapy and thereafter as judged clinically appropriate.
Patients with depression should be treated for a sufficient period of at least 6 months to ensure that they are free from symptoms.
2- Obsessive-compulsive disorder: The recommended dose is 20 mg daily. Although there may be an increased potential for undesirable effects at higher doses, in some patients, if after two weeks there is insufficient response to 20 mg, the dose may be increased gradually up to a maximum of 60 mg.
3- Bulimia nervosa: A dose of 60mg/day is recommended. Long-term efficacy (more than 3 months) has not been demonstrated in bulimia nervosa.
All indications: The recommended dose may be increased or decreased. Doses above 80 mg/day have not been systematically evaluated.
Children and adolescents aged 8 years and above:
Treatment should be initiated and monitored under specialist supervision.
The starting dose is 10mg/day. Dose adjustments should be made carefully,
on an individual basis, to maintain the patient at the lowest effective dose.
After one to two weeks, the dose may be increased to 20mg/day.
Due to higher plasma levels in lower-weight children, the therapeutic effect may be achieved with lower doses.
Caution is recommended when increasing the dose and the daily dose should generally not exceed 40mg. Maximum recommended dose is 60mg/day.
Patients with hepatic impairment:
A lower or less frequent dose (e.g. 20mg every second day) should be considered in patients with hepatic impairment.
Withdrawal symptoms seen on discontinuation of fluoxetine:
- Abrupt discontinuation should be avoided. When stopping treatment with fluoxetine the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of withdrawal reactions.
- The risk of withdrawal symptoms may be dependent on several factors, including the duration and dose of therapy and the rate of dose reduction.
Symptoms: Dizziness, sensory disturbances, sleep disturbances, asthenia, agitation or anxiety, nausea and/or vomiting, tremor, and headache.
Generally, these symptoms are mild to moderate.
- Symptoms: Symptoms of overdose have included nausea, vomiting, seizures, cardiovascular dysfunction ranging from asymptomatic arrhythmias or ECG changes, pulmonary dysfunction.
- Management: Cardiac and vital signs monitoring are recommended, along with general symptomatic and supportive measures. No specific antidote is known.
Carton pack contains 3 blisters of PVdC each of 10 film coated tablets, with leaflet.