Reboxetine Brand name: Edronax
Drug monograph
May 2000
Contents
Indications
Reboxetine is indicated for the treatment of depressive illness and for maintaining the clinical improvement in patients initially responding to treatment.
The remission of the acute phase of the depressive illness is associated with an improvement in the patient's quality of life in terms of social adaptation.
Safety
Contraindications
Hypersensitivity to reboxetine or any other components of the product.Warnings & Precautions
Since rare cases of seizures have been reported in clinical studies, reboxetine should be given under close supervision to subjects with a history of convulsive disorders and it should be discontinued if the patient develops seizures.Combined usage of MAO inhibitors and reboxetine should be avoided.
As with all antidepressants, switches to mania-hypomania have occurred. Close supervision of bipolar patients is recommended.
The risk of a suicidal attempt is inherent in depression and may persist until significant remission occurs; close patient supervision during initial drug therapy is recommended.
Caution is recommended in patients with current evidence of urinary retention and glaucoma.
Orthostatic hypotension has been observed with greater frequency at doses higher than the maximum recommended. Close supervision is recommended when administering reboxetine with other drugs known to lower blood pressure.
Pregnancy and Lactation
There are no adequate and well-controlled studies in pregnant women. Reboxetine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.While no information on the excretion of reboxetine in maternal milk in humans is available, reboxetine administration is not recommended in women who are breast feeding.
Overdose
In a few cases, doses higher than that recommended were administered to patients (12 to 20 mg/day) for a period ranging from a few days to a few weeks during clinical studies. Treatment-emergent adverse events included postural hypotension, anxiety and hypertension.Two cases of self-overdosing with up to 52 mg of reboxetine have been reported. No serious adverse events were observed.
In the case of overdose, close supervision including monitoring of cardiac function and vital signs is recommended.
Adverse Events
In placebo-controlled studies of 8 weeks duration or less, adverse events were reported in approximately 70% of reboxetine-treated patients and in approximately 60% of placebo-treated patients. Discontinuation rates for adverse events were similar between reboxetine- and placebo-treated patients and were less than 10%Adverse events that occurred with statistically greater frequency in reboxetine-treated patients than in placebo-treated patients include: dry mouth, constipation, insomnia, increased sweating, tachycardia, vertigo, urinary hesitance/retention and impotence. Impotence was mainly observed in patients treated with doses greater than 8 mg/day.
The only modification in vital signs was an increase in heart rate upon standing. Apart from tachycardia, no consistent changes in ECG tracings were observed during reboxetine treatment in adult patients.
In studies of longer than 8 weeks, newly emergent adverse events were reported in approximately 30% of the reboxetine-treated patients and approximately 25% of the placebo-treated patients. The adverse event profile for the studies of longer than 8 weeks was consistent with those for studies of 8 weeks or less. These adverse events were associated with discontinuation rates of 4% and 1%, respectively. Constipation was the only event which was observed more commonly in the reboxetine-treated group.
Adverse events occurring during discontinuation were infrequent and occurred in approximately 4% of the reboxetine-treated patients and approximately 6% of placebo-treated patients.
Interactions
In vitro studies have shown that reboxetine does not inhibit the activity of the following cytochrome P-450 isozymes: CYP1A2, CYP2C9, CYP2C19 and CYP2E1. At high concentrations, reboxetine inhibits CYP2D6, but the clinical significance of this observation is unknown. In vitro studies show that reboxetine is very weak inhibitor of CYP3A4.In vitro metabolism studies indicate that reboxetine is primarily metabolized by the CYP3A4 isozyme of cytochrome P450; reboxetine is not metabolized by CYP2D6. Therefore, compounds that decrease the activity of CYP3A4 would be expected to increase plasma concentrations of reboxetine. In a study in healthy volunteers, ketoconazole, a potent inhibitor of CYP3A4, was found to increase plasma concentrations of the reboxetine enantiomers by approximately 50%.
No significant reciprocal pharmacokinetic interaction has been found between reboxetine and lorazepam.
In an in vivo multiple dose study performed in healthy volunteers, no clinically significant interaction between fluoxetine and reboxetine was observed. Reboxetine does not appear to potentiate the effect of alcohol on cognitive functions in healthy volunteers.
Use of reboxetine concomitantly with other antidepressants (tricyclics, MAO inhibitors, SSRIs and lithium) has not been evaluated during clinical studies.
The extent of absorption of reboxetine is not significantly influenced by concomitant food intake.
Dosing (Posology)
Reboxetine tablets are for oral administration.
The onset of the clinical effect is generally seen after 14 days from treatment start.
Use in adults
The recommended therapeutic dose is 4 mg BID (8 mg/day) administered orally. After 3 weeks, the dose can be increased up to 10 mg/day in case of incomplete clinical response.Use in the elderly (age greater than 65)
The recommended therapeutic dose is 2 mg BID (4 mg/day) administered orally. This dose can be increased up to 6 mg/day in case of incomplete clinical response after 3 weeks from starting reboxetine.Use in children
There are no data available on the use of reboxetine in children.Use in patients with renal or hepatic insufficiency
The starting dose in patients with renal or moderate to severe hepatic insufficiency should be 2 mg BID which can be increased based on patient tolerance.
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