PROZAC^® 20

PROZAC 20 capsules are presented as size 3, green/cream capsules bearing the identicode "Lilly 3105" printed in black ink on both the capsule cap and base. Each capsule contains fluoxetine hydrochloride equivalent to 20 mg fluoxetine.

PROZAC 20 Dispersible tablets are white uncoated elongated scored tablets with an imprint. Each dispersible tablet contains fluoxetine hydrochloride equivalent to 20 mg fluoxetine.

Absorption and distribution

Fluoxetine is well absorbed after oral administration. Peak plasma concentration is reached in six to eight hours. Fluoxetine is extensively bound to plasma proteins. Fluoxetine is widely distributed. Steady-state plasma concentrations are achieved after dosing for several weeks. Steady-state concentrations after prolonged dosing are similar to concentrations seen at four to five weeks.

Metabolism and excretion

Fluoxetine is extensively metabolised in the liver to norfluoxetine and a number of other, unidentified metabolites which are excreted in urine. The elimination half-life of fluoxetine is four to six days and that of its active metabolite is four to 16 days.

Pharmacodynamic properties - The aetiology of premenstrual dysphoric disorder is unknown, but endogenous steroids (neuro and/or ovarian) involved in the menstrual cycle may interrelate with neuronal serotonergic activity.

Clinical data premenstrual dysphoric disorder (PMDD): In clinical trials fluoxetine was shown to be effective in relieving both the cyclical mood changes and physical symptoms (tension, irrritability and dsyphoria, bloating and breast tenderness) associated with PMDD.

Depression and it's associated anxiety,

Bulimia nervosa,

Obsessive-Compulsive disorder and

Premenstrual dysphoric disorder - a severe form of PMS.

Diagnosis of PMDD: The essential features of PMDD are clear and established cyclicity of symptoms (occurring during the last week of the luteal phase in most menstrual cycles) such as depressed mood, anxiety, affective lability, and physical symptoms such as breast tenderness or swelling, headaches, joint or muscle pain, bloating, and weight gain. PMDD is a severe clinical entity and is distinguished from the broader premenstrual syndrome by the intensity of its symptoms (particularly mood symptoms) and the extent to which it interferes with social and/or occupational function.

20 mg per day is the recommended initial dose.

60 mg per day is the recommended dose.

20 mg to 60 mg per day is the recommended dose.

20 mg per day is recommended continuously throughout the menstrual cycle. Initial treatment should be limited to six months, after which patients should be reassessed regarding the benefit of continued therapy.

The recommended dose may be increased or decreased. Doses above 80 mg/day have not been systematically evaluated.

There are no data to suggest that alternate dosing is required on the basis of age alone.

Safety and effectiveness in children have not been established.

PROZAC 20 may be administered with or without food.

A lower or less frequent dose should be considered in patients with hepatic impairment, with concurrent diseases, or who are taking multiple medications.

PROZAC 20 is contraindicated in patients known to be hypersensitive to fluoxetine.

PROZAC 20 should not be used in combination with a monoamine oxidase inhibitor (MAOI) or within a minimum of 14 days of discontinuing treatment with a MAOI. At least five weeks should elapse between discontinuation of PROZAC 20 and initiation of therapy with a MAOI. If PROZAC 20 has been prescribed chronically and/or at a high dose, a longer interval should be considered. Serious and fatal cases of serotonin syndrome (which may resemble and be diagnosed as neuroleptic malignant syndrome) have been reported in patients treated with fluoxetine and a MAOI in close temporal proximity.

Rash

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 possible allergic phenomena for which an alternative aetiology cannot be identified PROZAC 20 should be discontinued.

Seizures

As with other antidepressants, PROZAC 20 should be introduced cautiously in patients who have a history of seizures.

Hyponatraemia

Cases of hyponatraemia (some with serum sodium lower than 110 mmol/L) have been reported. The majority of these cases occurred in elderly patients and in patients treated with diuretics or otherwise volume-depleted.

Glycaemic Control

In patients with diabetes, hypoglycaemia has occurred during therapy with PROZAC 20 and hyperglycaemia has developed following discontinuation. Insulin and/or oral hypoglycaemic dosage may need to be adjusted when PROZAC 20 therapy is initiated or discontinued.

Carcinogenesis, mutagenesis, impairment of fertility

There is no evidence of carcinogenicity, mutagenicity or impairment of fertility from in vitro or animal studies.

Pregnancy

Experimental animal studies do not indicate direct or indirect harmful effects, with respect to the development of the embryo or foetus or the course of gestation. Because animal reproduction studies are not always predictive of human response, this medicine should be used during pregnancy only if clearly needed.

Lactation

Fluoxetine is excreted in human milk; therefore, caution should be exercised when PROZAC 20 is administered to nursing women.

Labour and delivery

The effect of PROZAC 20 on labour and delivery in humans is unknown.

Effects on ability to drive and use machines

Psychoactive medicines may impair judgement, thinking, or motor skills. Patients should be advised to avoid driving a car or operating machinery until they are reasonably certain that their performance is not affected.

Discontinuation Symptoms

Symptoms following discontinuation have been reported in association with antidepressants including selective serotonin reuptake inhibitors (SSRIs). Common symptoms include dizziness, paraesthesia, headache, anxiety and nausea. These symptoms are less likely to occur with fluoxetine than other antidepressants because both fluoxetine and its active metabolite have relatively long half-lives.

The prescriber should be aware that the information presented in Table 1 cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of medicine and non-medicine factors to the side effect incidence rate in the population studied.

The following events have not been reported in clinical trials of fluoxetine, but have been reported in clinical practice and are associated with fluoxetine therapy:

Serotonin syndrome [see Contraindications with MAOIs], inappropriate secretion of ADH, very rare idiosyncratic hepatitis.

Because fluoxetine has the potential to inhibit the cytochrome P450IID6 isoenzyme, therapy with medications that are predominantly metabolised by the P450IID6 system and that have a relatively narrow therapeutic index 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 five weeks. If PROZAC 20 is added to the treatment range of a patient already receiving such a medicine, the need for decreased dose of the original medication should be considered.

Changes in the blood levels of phenytoin, carbamazepine, haloperidol, clozapine, diazepam, alprazolam, lithium, 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.

Because fluoxetine is tightly bound to plasma protein, the administration of PROZAC 20 to a patient taking another medicine that is tightly bound to protein may cause a shift in plasma concentrations of either medicine.

Altered anti-coagulant effects (laboratory values and/or clinical signs and symptoms), with no consistent pattern, but increased bleeding, have been reported uncommonly when PROZAC 20 is co-administered with warfarin. As is prudent in concomitant use of warfarin with many other medicines, patients receiving warfarin therapy should receive careful monitoring when PROZAC 20 is initiated or stopped.

There have been rare reports of prolonged seizures in patients on PROZAC 20 receiving ECT treatment.

The long elimination half-lives of fluoxetine and its principal metabolite, norfluoxetine, are of potential consequence when medicines are prescribed which might interact with either substance following the discontinuation of PROZAC 20.

Cases of overdose of fluoxetine alone usually have a mild course. Symptoms of overdose have included nausea, vomiting, seizures, and signs of CNS excitation. Fatality attributed to overdose of fluoxetine alone has been extremely rare.

Cardiac and vital signs monitoring is recommended along with general symptomatic and supportive measures. No specific antidote is known. Forced diuresis, dialysis, haemoperfusion, and exchange transfusion are unlikely to be of benefit. In managing overdosage, consider the possibility of multiple medicine involvement.

20 mg capsules: Three years < 30°C
Dispersible tablets: Two years < 25°C

Capsules: none
Dispersible tablets: Disperse the tablet in approximately 100 mL water.

None known.

Prescription Medicine.

Capsules: Each pack contains 30 capsules in 3 platforms of 10 capsules each.
Dispersible tablets: Each pack contains 30 tablets in 3 platforms of 10 tablets each.

Physicians are advised to discuss the following issues with patients for whom they prescribe fluoxetine:
Because PROZAC 20 may impair judgement, thinking, or motor 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.
Patients should be advised to inform their physician if they are taking or plan to take any prescription or over-the-counter medicines, or alcohol.
Patients should be advised to inform their physician if they become pregnant or intend to become pregnant during therapy.
Patients should be advised to notify their physician if they are breast feeding an infant.
Patients should be advised to notify their physician if they develop a rash or hives.

Capsules: starch, silicone fluid, gelatin.
Dispersible tablets: microcrystalline cellulose, sodium saccharin, mannitol, sorbitol, aniseed flavouring, peppermint flavouring, colloidal anhydrous silica, pregelatinised starch, sodium stearyl fumarate, crospovidone.