Prozac 20 mg Tablets

Major depressive episodes

Bulimia nervosa

Obsessive-compulsive disorder: The obsessions or compulsions must be experienced as intrusive, markedly distressing, time consuming or interfering significantly with the person's social or occupational functioning.

Posology

Major depressive episode

Adults and elderly: A dose of 20 mg/day is recommended, preferably in the morning.

Bulimia nervosa

A dose of 60 mg/day is recommended.

Obsessive-compulsive disorder

A dose of 20 to 60 mg/day is recommended. The recommended dose may be increased or decreased. PROZAC 20 capsules cannot be used for downward dose titration. Doses above 80 mg/day are not recommended for any indication. Upward dose titration is advised at intervals of several weeks due to the kinetic properties of PROZAC 20 (see section 5.2). PROZAC 20 may be administered with or without food.

Usage in the elderly

PROZAC 20 should be used with caution in all elderly patients, particularly if they have systemic illness or are receiving multiple medications for concomitant diseases. Dosages over 20 mg per day are not recommended (see section 5.2).

Hepatic impairment and/or concurrent disease

A lower or less frequent dose should be considered in patients with hepatic impairment and concurrent diseases.

Withdrawal/discontinuation

Discontinuation of PROZAC 20 may lead to withdrawal symptoms, including dizziness, paraesthesia, headache, insomnia, tremor, confusion, sensory disturbances, asthenia, agitation, anxiety and nausea (see section 4.4).

Method of administration

For oral administration to adults only.

• Hypersensitivity (allergy) to the active substance, fluoxetine, or to any of the excipients listed in section 6.1.
• Severe renal failure (GFR < 30 ml/min).
• Concomitant use with linezolid.
• Concomitant use with metoprolol when used in cardiac failure.
• Concomitant use with pimozide.
• Concomitant use with monoamine oxidase inhibitors (MAOI) or within 14 days of discontinuation of therapy of MAOI (see section 4.4).

Paediatric use

Safety and efficacy in children below 18 years of age have not been established.

As improvement may not occur during the first two weeks of treatment, patients should be closely monitored during this period.

Suicide/suicidal thoughts or clinical worsening

Patients with major depressive disorder, both adults and children, may experience worsening of their depression and/or the emergence of suicidal ideation and behaviour, whether or not they are taking antidepressant medicines. This risk may persist until significant remission occurs. Isolated cases of suicidal ideation and suicidal behaviours have been reported during PROZAC 20 therapy or early after treatment discontinuation. Although a causal role for PROZAC 20 alone in inducing such behaviours has not been established, some pooled analyses from studies of patients using antidepressants in psychiatric conditions indicate an increased risk for suicidal ideation and suicidal behaviours in paediatric and young adult (< 25 years of age) patients.

In an analysis of controlled trials in adults with major depressive disorder, the following were risk factors for suicidality:

Prior to treatment:

• greater severity of depression
• presence of thoughts of death

During treatment:

• worsening of depression
• development of insomnia

Patients being treated with PROZAC 20 should be observed closely for clinical worsening and suicidality, especially at the beginning of a course of therapy or at any time of dose changes, either increases or decreases.

Medical practitioners should encourage patients of all ages to report any distressing thoughts or feelings at any time.

Because of the possibility of co-morbidity between major depressive disorder and other psychiatric disorders (e.g. obsessive-compulsive disorders) and non-psychiatric disorders, the same precautions observed when treating patients with major depressive disorder should be observed when treating patients with other psychiatric and non-psychiatric disorders.

Serotonin syndrome

A serotonin syndrome, which may be confused with neuroleptic malignant syndrome, may occur with the use of PROZAC 20. This syndrome is characterised by the clustering of clinical features of changes in mental state (confusion, disorientation, agitation) and neuromuscular activity (myoclonus, hyper-reflexia, tremor, rigidity, dyscoordination in combination with autonomic dysfunction (especially fever, sweating, diarrhoea). The serotonin syndrome has been seen in temporal association with the use of monoamine oxidase inhibitors and with other serotonergic medication, but may occur in the absence of any concomitant medication. PROZAC 20 should be stopped immediately as serious morbidity and death may follow the serotonin syndrome.

Monoamine oxidase inhibitors

Cases of serious and sometimes fatal reactions (including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs and mental status changes that include extreme agitation progressing to delirium and coma) have been reported in patients receiving PROZAC 20 in combination with monoamine oxidase inhibitors (MAOI) and in patients who have recently discontinued PROZAC 20 and are then started on a MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Therefore PROZAC 20 is contraindicated in combination with a MAOI or within 14 days of discontinuing therapy with a MAOI. Since PROZAC 20 and its major metabolite have very long elimination half-lives, at least 5 weeks should be allowed after stopping PROZAC 20 before starting a MAOI. If PROZAC 20 has been prescribed chronically and/or at a high dose, a longer interval should be considered (see sections 4.3 and 4.5).

Cardiovascular effects

Clinical experience in acute cardiac disease is limited, therefore caution is advisable. Cases of QT interval prolongation and ventricular dysrhythmia including torsades de pointes have been reported during the post-marketing period. PROZAC 20 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 dysrhythmias (e.g., hypokalaemia, hypomagnesaemia, bradycardia, acute myocardial infarction or uncompensated heart failure) or increased exposure to PROZAC 20 (e.g., hepatic impairment), or concomitant use with medicinal products known to induce QT prolongation and/or torsade de pointes. If patients with stable cardiac disease are treated, an ECG review should be considered before treatment is started. If signs of cardiac dysrhythmia occur during treatment with fluoxetine, the treatment should be withdrawn, and an ECG should be performed.

Mania

Antidepressants should be used with caution in patients with a history of mania/hypomania. As with all antidepressants, fluoxetine should be discontinued in any patient entering a manic phase.

Rash and possibly allergic events

Rash, anaphylactoid events and progressive systemic events, sometimes serious and involving skin, kidney, liver or lung, have been reported in patients taking PROZAC 20. Upon the appearance of rash or of other possibly allergic phenomena, PROZAC 20 should be discontinued.

Seizures

PROZAC 20 should be introduced cautiously in patients who have a history of seizures. PROZAC 20 should be discontinued in any patient who develops seizures. PROZAC 20 should be avoided in patients with uncontrolled epilepsy; patients with controlled epilepsy should be carefully monitored.

Electroconvulsive therapy (ECT)

There have been reports of prolonged seizures in patients on PROZAC 20 receiving electroconvulsant treatment (see section 4.5).

Tamoxifen

PROZAC 20, a potent inhibitor of CYP2D6, may lead to reduced concentrations of endoxifen, one of the most important active metabolites of tamoxifen. Therefore, PROZAC 20 should whenever possible be avoided during tamoxifen treatment (see section 4.5).

Hepatic/renal function

PROZAC 20 is extensively metabolised by the liver and excreted by the kidneys. A lower dose, e.g. alternate day dosing, is recommended in patients with significant hepatic dysfunction or mild to moderate renal failure (GFR 30 to 80 ml/min).

Weight loss

PROZAC 20 may cause loss of mass which could be undesirable in underweight depressed patients.

Diabetes

In patients with diabetes, PROZAC 20 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 when fluoxetine therapy is initiated or discontinued.

Haemorrhage

There have been reports of altered platelet function and/or abnormal results from laboratory studies in patients taking fluoxetine. There have also been reports of abnormal bleeding in several patients taking fluoxetine, including cutaneous bleeding abnormalities (e.g. ecchymosis and purpura) and other haemorrhagic manifestations (e.g. gynaecological haemorrhages, gastrointestinal bleedings and other cutaneous or mucous bleedings) (see section 4.5). Caution is advised in patients taking SSRIu2019s, particularly in concomitant use with oral anticoagulants, drugs known to affect platelet function (e.g. atypical antipsychotics such as clozapine, phenothiazines, most TCAu2019s, aspirin, NSAIDu2019s) or other medicines which may increase risk of bleeding as well as in patients with a history of bleeding disorders (see section 4.5).

Akathisia/psychomotor restlessness

Development of severe psychomotor activation (e.g. agitation, akathisia, panic) was also a risk factor during treatment with PROZAC 20. The presence or emergence of these conditions prior to or during therapy suggests that consideration should be given to increased clinical monitoring or possible modification of therapy.

There have been reports of extrapyramidal symptoms associated with the use of PROZAC 20 and of aggravation of Parkinsonu2019s disease in patients taking PROZAC 20. PROZAC 20 should therefore be used with care in patients with extrapyramidal disorders.

Mydriasis

Mydriasis has been reported in association with PROZAC 20; therefore, caution should be used when prescribing fluoxetine in patients with raised intraocular pressure or those at risk of acute narrow-angle glaucoma.

Withdrawal symptoms on discontinuation of treatment

Discontinuation of PROZAC 20 may lead to withdrawal symptoms, including dizziness, paraesthesia, headache, insomnia, tremor, confusion, sensory disturbances, asthenia, agitation, anxiety and nausea (see section 4.2). If the decision is made to discontinue treatment, PROZAC 20 should be tapered over a period of at least one to two weeks, according to the patientu2019s needs (see section 4.2).

Sexual dysfunction

Selective serotonin reuptake inhibitors (SSRI), such as PROZAC 20, may cause symptoms of sexual dysfunction (see section 4.8). There have been reports of long-lasting sexual dysfunction where the symptoms have continued despite discontinuation of treatment.

General

The following symptoms have been reported in patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and non-psychiatric: anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania and mania. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, consideration should be given to changing the therapeutic regimen, including possibly discontinuing PROZAC 20 in patients for whom such symptoms are severe, abrupt in onset or were not part of the patientu2019s presenting symptoms.

The long elimination half-lives of fluoxetine and its active metabolite should be borne in mind (see section 5.2) when considering pharmacodynamic or pharmacokinetic medicine interactions, or the potential consequence when medicines are prescribed that might interact with either substance following the discontinuation of PROZAC 20.

Medicines metabolised by cytochrome CYP2D6 isoenzyme

PROZAC 20 has the potential to inhibit the cytochrome CYP2D6 isoenzyme, therapy with medications that are predominantly metabolised by the P450IID6 system and that have a relatively narrow therapeutic index (such as flecainide, propafenone and nebivolol) and those that are titrated, but also with atomoxetine, carbamazepine, tricyclic antidepressants and risperidone. They should be initiated at the low end of the dose range if a patient is receiving PROZAC 20 concurrently or has taken it in the previous 5 weeks. If PROZAC 20 is added to the treatment regimen of a patient already receiving such a medicine, the need for decreased dose of the original medication should be considered.

Metoprolol

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 (see section 4.3).

Monoamine oxidase inhibitors

PROZAC 20 should not be used concomitantly with monoamine oxidase inhibitors (see sections 4.3 and 4.4).

CNS active medicines

Caution is advised if the concomitant administration of PROZAC 20 and CNS active medicines, including lithium, is required. There have been reports of both increased and decreased lithium levels when used concomitantly with fluoxetine. Lithium levels should be monitored.

Changes in blood levels of phenytoin, carbamazepine, haloperidol, clozapine, diazepam, alprazolam, imipramine and desipramine, and in some cases clinical manifestations of toxicity, have been observed. Consideration should be given to using conservative titration schedules of the concomitant medicine and monitoring of clinical status.

Concomitant use of other medicines with serotonergic activity (e.g. Serotonin and Norepinephrine Reuptake Inhibitors, Selective Serotonin Reuptake Inhibitors, such as triptans, tramadol, tryptophane, selegiline, or St. Johnu2019s Wort) may result in serotonin syndrome. Therefore, the concomitant use of PROZAC 20 with these medicines should be undertaken with caution, with closer and more frequent clinical monitoring (see section 4.4).

There have been greater than 2-fold increases of previously stable plasma levels of other antidepressants when PROZAC 20 has been administered in combination with these medicines. Patients receiving PROZAC 20 in combination with tryptophan have been reported to experience adverse reactions, including agitation, restlessness and gastrointestinal distress. The half-life of concurrently administered diazepam may be prolonged.

Medicines affecting haemostasis

PROZAC 20 use may increase the risk of bleeding abnormalities. Concomitant use of aspirin, NSAIDS, other antiplatelet aggregation inhibitors, warfarin and other anticoagulants may add to this risk. Additional clinical evaluation and more frequent INR monitoring if receiving warfarin, should be implemented. Dose adjustments may be necessary during the initiation, ongoing treatment and/or discontinuation of PROZAC 20.

Tamoxifen

Pharmacokinetic interaction between CYP2D6 inhibitors and tamoxifen, showing a 65 to 75 % reduction in plasma levels of one of the more active forms of the tamoxifen, i.e. endoxifen, has been reported in the literature. Reduced efficacy of tamoxifen has been reported with concomitant usage of some SSRI antidepressants in some studies. As a reduced effect of tamoxifen cannot be excluded, co-administration with potent CYP2D6 inhibitors, such as PROZAC 20, should whenever possible be avoided (see section 4.4).

Alcohol

In formal testing, fluoxetine did not raise blood alcohol levels or enhance the effects of alcohol. However, the combination of SSRI treatment and alcohol is not advisable.

QT interval prolongation

Pharmacokinetic and pharmacodynamic studies between fluoxetine and other medicinal products that prolong the QT interval have not been performed. An additive effect of fluoxetine and these medicinal products cannot be excluded. Therefore, co-administration of fluoxetine, as in PROZAC 20, with medicinal products that prolong the QT interval, such as Class IA and III antiarrhythmics, antipsychotics (e.g. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobial medicines (e.g. sparfloxacin, moxifloxacin, erythromycin IV, pentamidine), anti-malaria treatment particularly halofantrine, certain antihistamines (astemizole, mizolastine), should be used with caution (see sections 4.4, 4.8 and 4.9).

Cyproheptadine

There are individual case reports of reduced antidepressant activity of fluoxetine, as in PROZAC 20, when used in combination with cyproheptadine.

Medicines inducing hyponatremia

Hyponatremia is an undesirable effect of fluoxetine, as in PROZAC 20. Use in combination with other medicines associated with hyponatremia (e.g. diuretics, desmopressin, carbamazepine and oxcarbazepine) may lead to an increased risk (see section 4.8).

Medicines lowering the epileptogenic threshold

Seizures are an undesirable effect of fluoxetine, as in PROZAC 20. Use in combination with other medicines which may lower the seizure threshold (for example, TCAs, other SSRIs, phenothiazines, butyrophenones, mefloquine, chloroquine, bupropion, tramadol) may lead to an increased risk.

Plasma protein binding

Fluoxetine is bound to plasma protein and concurrent administration may alter plasma concentrations of other plasma protein bound medicines, e.g. warfarin, digitoxin, or conversely, fluoxetine binding may be changed by other medicines.

Electroconvulsive therapy (ECT)

There have been reports of prolonged seizures in patients on PROZAC 20 receiving ECT treatment (see section 4.4)

Pregnancy

Safety in pregnancy has not been demonstrated. PROZAC 20 use should be considered during pregnancy only if the potential benefit justifies the potential risk to the foetus, taking into account the risks of untreated depression. Results of a number of epidemiological studies assessing the risk of fluoxetine exposure in early pregnancy have been inconsistent and have not provided conclusive evidence of an increased risk of congenital malformations. However, one meta-analysis suggests a potential risk of cardiovascular defects in infants of women exposed to PROZAC 20 during the first trimester of pregnancy compared to infants of women who were not exposed to PROZAC 20.

Use in the third trimester

At the end of pregnancy, caution should be exercised, as transitory withdrawal symptoms (e.g. transient jitteriness, difficulty feeding, tachypnoea and irritability) have been reported rarely in the neonate after maternal use near term.

Some neonates exposed to PROZAC 20 late in the third trimester developed complications resulting in prolonged hospitalisation, respiratory support and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs, or possibly, withdrawal syndrome. In some cases, the clinical picture is consistent with serotonin syndrome (see section 4.4).

PROZAC 20 use late in the third trimester of pregnancy may increase the risk of persistent pulmonary hypertension in the newborn. Observational data indicate an increased risk (less than 2-fold) of postpartum haemorrhage following SSRI/SNRI exposure within the month prior to birth (see sections 4.4, 4.8).

Breastfeeding

Fluoxetine and its metabolite norfluoxetine, are known to be excreted in human breast milk. Adverse events have been reported in breastfeeding infants. If treatment with PROZAC 20 is considered necessary, discontinuation of breastfeeding should be considered; however if breastfeeding is continued, the lowest effective dose of PROZAC 20 should be prescribed.

Fertility

Animal data have shown that fluoxetine may affect sperm quality (see section 5.3). Human case reports with some SSRIu2019s have shown that an effect on sperm quality is reversible. Impact on human fertility has not been observed so far.

Although PROZAC 20 has been shown not to affect psychomotor performance in healthy volunteers, PROZAC 20 may impair judgement, thinking or motor skills. Patients should be cautioned that their ability to perform potentially hazardous tasks (e.g. driving a motor vehicle or operating machinery) may be impaired. They should refrain from doing so until certain how they are affected by PROZAC 20.

a. Summary of the safety profile

The most commonly reported adverse reactions in patients treated with fluoxetine were headache, nausea, insomnia, fatigue and diarrhoea. Undesirable effects may decrease in intensity and frequency with continued treatment and do not generally lead to cessation of therapy.

b. Tabulated list of adverse reactions

Clinical Trial Data: Events are classified within body system categories using the following frequencies: very common adverse events ( u2265 1/10), common adverse events (u2265 1/100, < 1/10), uncommon adverse events (u2265 1/1 000, < 1/100), rare events (u2265 1/10 000, < 1/1 000) , not known (cannot estimate from the available data).

Very Common Common Uncommon Rare Not known

Blood and lymphatic system disorders

• Thrombocytopenia
• Neutropenia
• Leucopenia

Immune system disorders

• Anaphylactic reaction
• Serum sickness

Endocrine disorders

• Inappropriate antidiuretic hormone secretion

Metabolism and nutrition disorders

• Decreased appetite
• Hyponatraemia

Psychiatric disorders

• Insomnia
• Anxiety
• Nervousness
• Restlessness
• Tension
• Libido decreased
• Sleep disorder
• Abnormal dreams
• Depersonalisation
• Elevated mood
• Euphoric mood
• Thinking abnormal
• Orgasm abnormal
• Bruxism
• Suicidal thoughts and behaviour
• Hypomania
• Mania
• Hallucinations
• Agitation
• Panic attacks
• Confusion
• Dysphemia
• Aggression

Nervous system disorders

• Headache
• Disturbance in attention
• Dizziness
• Dysgeusia
• Lethargy
• Somnolence
• Tremor
• Psychomotor hyperactivity
• Dyskinesia
• Ataxia
• Balance disorder
• Myoclonus
• Memory impairment
• Convulsion
• Akathisia
• Buccoglossal syndrome
• Serotonin syndrome

Eye disorders

• Vision blurred
• Mydriasis

Ear and labyrinth disorders

• Tinnitus

Cardiac disorders

• Palpitations
• Electrocardiogram QT prolonged (QTcF u2265 450 msec)
• Ventricular arrhythmia including torsades de pointes

Vascular disorders

• Flushing
• Hypotension
• Vasculitis
• Vasodilatation

Respiratory, thoracic and mediastinal disorders

• Yawning
• Dyspnoea
• Epistaxis
• Pharyngitis
• Pulmonary events (inflammatory processes of varying histopathology and/or fibrosis)

Gastrointestinal disorders

• Diarrhoea
• Nausea
• Vomiting
• Dyspepsia
• Dry mouth
• Dysphagia
• Gastrointestinal haemorrhage
• Oesophageal pain

Hepato-biliary disorders

• Idiosyncratic hepatitis

Skin and subcutaneous tissue disorders

• Rash
• Urticaria
• Pruritus
• Hyperhidrosis
• Alopecia
• Increased tendency to bruise
• Cold sweat
• Angioedema
• Ecchymosis
• Photosensitivity reaction
• Purpura
• Erythema multiforme
• Stevens-Johnson syndrome
• Toxic Epidermal Necrolysis (Lyell Syndrome)

Musculoskeletal and connective tissue disorders

• Arthralgia
• Muscle twitching
• Myalgia

Renal and urinary disorders

• Frequent urination
• Dysuria
• Urinary retention
• Micturition disorder

Reproductive system and breast disorders

• Gynaecological bleeding
• Erectile dysfunction
• Ejaculation disorder
• Sexual dysfunction
• Galactorrhoea
• Hyperprolactinaemia
• Priapism
• Postpartum haemorrhage

General disorders and administration site conditions

• Fatigue
• Feeling jittery
• Chills
• Malaise
• Feeling abnormal
• Mucosal haemorrhage
• Feeling cold
• Feeling hot

Investigations

• Weight decreased
• Transaminases increased
• Gamma-glutamyltransferase increased

1 Includes anorexia

2 Includes early morning awakening, initial insomnia, middle insomnia

3 Includes loss of libido

4 Includes nightmares

5 Includes anorgasmia

6 Includes completed suicide, depression suicidal, intentional self-injury, self-injurious ideation, suicidal behaviour, suicidal ideation, suicide attempt, morbid thoughts, self injurious behaviour. These symptoms may be due to underlying disease

7 Includes hypersomnia, sedation

8 Based on ECG measurements from clinical trials

9 Includes hot flush

10 Includes atelectasis, interstitial lung disease, pneumonitis

11 Includes most frequently gingival bleeding, haematemesis, haematochezia, rectal haemorrhage, diarrhoea haemorrhagic, melaena, and gastric ulcer haemorrhage

12 Includes erythema, exfoliative rash, heat rash, rash, rash erythematous, rash follicular, rash generalized, rash macular, rash macular-papular, rash morbilliform, rash papular, rash pruritic, rash vesicular, umbilical erythema rash

13 Includes pollakiuria

14 Includes cervix haemorrhage, uterine dysfunction, uterine bleeding, genital haemorrhage, menometrorhagia, menorrhagia, metrorrhagia, polymenorrhea, postmenopausal haemorrhage, uterine haemorrhage, vaginal haemorrhage

15 Includes ejaculation failure, ejaculation dysfunction, premature ejaculation, ejaculation delayed, retrograde ejaculation

16 Occasionally persisting after treatment discontinuation

17 This event has been reported for the therapeutic class of SSRIs/SNRIs (see sections 4.4, 4.6).

18 Includes asthenia

The following have been reported in association with PROZAC 20, but no causal relationship has been established: Aplastic anaemia, cerebral vascular accident, confusion, seizures, dyskinesia (including, for example, a case of buccal-lingual-masticatory syndrome, which resolved following drug discontinuation), eosinophilic pneumonia, gastrointestinal haemorrhage, hyperprolactinaemia, erythema multiforme, angioedema, movement disorders developing in patients with risk factors (including medicines associated with such events) and worsening of pre-existing movement disorders, neuroleptic malignant syndrome-like events, pancreatitis, suicidal ideation, pancytopenia, immune related haemolytic anaemia, thrombocytopenia, thrombocytopenic purpura, vaginal bleeding after withdrawal of the medication and violent behaviour.

See section 4.6 for information on side effects of persistent pulmonary hypertension in the newborn.

c. Description of selected adverse reactions

Suicide/suicidal thoughts or clinical worsening

Cases of suicidal ideation and suicidal behaviour have been reported during fluoxetine therapy or early after treatment discontinuation (see section 4.4).

Bone fractures

Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving SSRIs and TCAs. The mechanism leading to the risk is unknown.

Withdrawal symptoms seen on discontinuation of fluoxetine treatments

Discontinuation of fluoxetine commonly leads to withdrawal symptoms. 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. Generally these events are mild to moderate and are self-limiting, however, in some patients they may be severe and/or prolonged (see section 4.4). It is therefore advised that when PROZAC 20 treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see sections 4.2 and 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8. Alternately, report suspected adverse reactions to the company at [email protected].

Symptoms

Symptoms of overdose included nausea, vomiting, seizures, cardiovascular dysfunction ranging from asymptomatic dysrhythmias (including nodal rhythm and ventricular dysrhythmias) or ECG changes indicative of QTc prolongation to cardiac arrest (including very rare cases of Torsades de Pointes), pulmonary dysfunction and signs of altered CNS status ranging from excitation to coma.

Management

Cardiac and vital signs monitoring is recommended along with general symptomatic and supportive measures. There are no specific antidotes for PROZAC 20. Due to the large volume of distribution of PROZAC 20, forced diuresis, dialysis, haemoperfusion and exchange transfusion are unlikely to be of benefit. In managing overdosage, the possibility of multiple medicine involvement should be considered.