Kalxetin

KALXETIN^®
Fluoxetine HCl
capsule

Composition
Each capsule contains :
Fluoxetine HCl equivalent to Fluoxetine 10 mg or 20 mg

Pharmacology
Fluoxetine is a new oral antidepressant which is chemically unrelated to tricyclic, tetracyclic or other available antidepressants.

Its antidepressant action seems to be inhibition of CNS neuronal uptake of serotonin. Fluoxetine at clinically relevant doses has been shown to block the uptake of serotonin, but not of norepinephrine, into human platelets. In animal studies, fluoxetine is also a much more potent uptake inhibitor of serotonin than of norepinephrine. As a serotoninergic antidepressant, fluoxetine is also effective in the treatment of obsessive-compulsive disorder.
Antagonism of muscarinic, histaminergic and α-t- adrenergic receptors has been correlated with anticholinergic, sedative and cardiovascular effects of classical tricyclic antidepressants. Fluoxetine binds to these and other membrane receptors from brain tissue much less potently in vitro than do the tricyclics. A single oral dose of 40 mg produces peak plasma levels of 15-55 ng/mL after 6-8 hours. Food may delay its absorption but does not affect its bioavailability. Fluoxetine is 94.5% bound to plasma proteins, albumin and α-t- glycoprotein. Fluoxetine is extensively metabolized to an active metabolite, norfluoxetine, and a number of other metabolites. Norfluoxetine' s potency and selectivity as a serotonin uptake blocker is essentially equivalent to fluoxetine' s. The primary route of elimination is hepatic metabolism inactive metabolites excreted by the kidney. The elimination half- life of fluoxetine is 2-3 days, while that of norfluoxetine is 7-9 days. After 30 days of dosing at 40 mg/day, plasma concentrations of fluoxetine in the range of 91- 302 ng/mL and norfluoxetine 72-258 ng/mL. In cirrhotic patients, the elimination half life of fluoxetine increases from 2-3 days in normal subjects to 7.6 days, while that of norfluoxetine from 7-9 days to 12 days.

Indications
Treatment of depression.
Its efficacy is established for outpatients with major depressive disorder treated for 5 to 6 weeks.

Contraindications
KALXETIN^® is contraindicated in patients known to be hypersensitive to it.

Dosage and administration 
Initial treatment:
The initial dose is 20 mg/day in the morning. If no clinical improvement is observed after several weeks, the dose may be increased. Doses above 20 mg/day should be given bid (ie, morning and noon), and a maximum dose of 80 mg/day should not be exceeded. Like other antidepressants, the full antidepressant effect may be delayed until 4 weeks of treatment or longer. A lower or less frequent dosage should be used in hepatic and/or renal impairment, and should also be considered for patients, such as the elderly, with concurrent disease or on multiple medications.

Maintenance/ Continuation/ Extended treatment
It is not known how long a patient treated with fluoxetine should remain on it. In 1987, expert psychopharmacologists agreed that in general, acute episodes of depression require several months or longer of sustained pharmacologic therapy. Whether the dose of antidepressant needed to induce remission is identical to the dose needed to maintain and/or sustain euthymia is unknown.

Warnings and precautions

1. Fluoxetine may cause rash in 4 % of patients, associated with systemic signs or symptoms such as fever, leukocytosis, arthralgia, edema, carpal tunnel syndrome, respiratory distress and mild transaminase elevation, lymphadenopathy, proteinuria, etc. Although the association is not certain, and there is no sustained lasting injury, fluoxetine should be discontinued upon appearance of rash.
2. Fluoxetine may cause significant weight loss (more than 5% of body weight) in 13% of patients.
3. Fluoxetine may activate mania/ hypomania in approximately 1 % of patients. Other antidepressants, however, also activate mania/ hypomania in a small proportion of patients with major affective disorder.
4. Like other antidepressants, fluoxetine may cause seizures in 0.2% of patients. Therefore, fluoxetine should be introduced with care in patients with a history of seizures.
5. Fluoxetine has not been evaluated in patients with a recent history of myocardial infarction or unstable heart disease.
6. In patients with liver cirrhosis, a lower or less frequent dose should be used (see Pharmacology section).
7. Use with caution in patients with severe renal impairment : chronic treatment with fluoxetin have not been adequately evaluated.
8. Any psychoactive drug, including fluoxetine, may impair judgment, thinking, or motor skills, and patients should be cautioned about operating hazardous machinery, including motor vehicle, until they are reasonably certain that the drug treatment does not affect them adversely.
9. Usage during pregnancy : Reproduction studies in rats and rabbits at doses 9 and 11 times the maximum daily human dose (80 mg) respectively have revealed no evidence of harm to the fetus due to fluoxetine. However, there are no adequate and well-controlled studies pregnant women. Therefore, this drug should be used during pregnancy only if clearly needed.
10. The effect of fluoxetine on labor and delivery in humans is unknown.
11. Excretion of fluoxetine and its metabolites in human milk is unknown, therefore this drug should be used with caution in nursing women.
12. Safety and efficacy of fluoxetine in children have not been established.
13. No unusual adverse age - related events have been identified in elderly patients. However, the data are insufficient to rule out possible age-related differences during chronic use, particularly in elderly patients who have concomitant systemic illness or who are receiving concomitant drugs.
14. In patients with diabetes, KALXETIN^® may alter glycemic control. Hypoglycemia has occurred during therapy with KALXETIN^® and hyperglycemia has developed following discontinuation of the drug.

Drug interactions

1. Data on the effects of the combined use fluoxetine and MAO inhibitors are limited, therefore their combined use should be avoided. At least 14 days should elapse between discontinuation of a MAOI and initiation of fluoxetine treatment, and at least 5 weeks should elapse between discontinuation of fluoxetine and initiation of therapy with a MAOI.
2. Concurrent administration with diazepam may prolong the elimination half life of diazepam.
3. Displacement of plasma protein binding may occur when fluoxetine is used in combination with other drugs which are tightly bound to plasma proteins (eg, warfarin, digitoxin), resulting in increased free plasma levels and potentially adverse effects.
4. Combination of fluoxetine and tryptophan may cause agitation. restlessness, and GI distress.
5. Combination of fluoxetine with other CNS - active drugs has not been adequately evaluated, therefore this Combination should be used with caution.
6. The benefit of the combined use of ECT and fluoxetine has not been established. A single report of prolonged seizure in a patient on fluoxetine has been reported.

Adverse reactions
The most commonly observed adverse events were :

• Nervous system complaints, including anxiety, nervousness, and insomnia
• Drowsiness and fatigue or asthenia
• Tremor
• Sweating
• GI complaints, including anorexia, nausea, and diarrhea
• Dizziness or lightheadedness
• Chills
• Increased appetite
• Weight loss
• Abnormal dream and agitation
• Bronchitis, rhinitis and yawn

Overdosage
Until December 1987 there were 38 reports of acute overdose with fluoxetine, alone or in combination with other drugs and/or alcohol. Among these cases, there were 2 deaths in which fluoxetine was found in combination with other CNS-active drugs (maprotiline in one case, and codeine with temazepam in the other case). One case of overdose of fluoxetine alone (3000 mg) experienced 2 grandmal seizures that remitted spontaneously without specific anticonvulsant treatment.
The prominent symptoms of fluoxetine overdose were nausea, vomiting, agitation, restlessness, hypomania and other signs of CNS excitation. Except for the 2 deaths mentioned above, all other overdose cases recovered without residue.There are no specific antidote for fluoxetine. Management of overdose includes emesis or lavage or activated charcoal, and symptomatic and supportive measures.

Presentation 
Capsule 10 mg: Box of 3 strips x 10 capsules Reg. No. DKL0111618501B1
Capsule 20 mg: Box of 3 strips x 10 capsules Reg. No. DKL9311618501A1

Store below 30°C.

ON MEDICAL PRESCRIPTION ONLY.
HARUS DENGAN RESEP DOKTER.

PT KALBE FARMA Tbk.
Bekasi - Indonesia

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