Edronax

/ Pfizer

Use in adults: The recommended therapeutic dose is 4 mg BID (8 mg/day) administered orally. After 3-4 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. The dose can be increased up to 6 mg/day in case of incomplete clinical response after 3 weeks from starting reboxetine.
Use in children and adolescents under the age of 18 years: There are no data available on the use of reboxetine in children. Edronax should not be used in the treatment of children and adolescents under the age of 18 years.
Use in patients with renal or hepatic impairment: 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.
For full details see prescribing information.

Depression and as maintenance therapy in patients initially responding to treatmentt.

Hypersensitivity to the active substance or to any of the excipients.

Paediatric population
Reboxetine should not be used in the treatment of children and adolescents under the age of 18 years. Suicide-related behaviours (suicide attempt and suicidal thoughts), and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.
Seizures
Reboxetine has not been tested in patients with convulsive disorders in clinical studies and since rare cases of seizures have been reported in clinical studies, it should be given under close supervision to subjects with a history of convulsive disorders and it must be discontinued if the patient develops seizures.
Serotonin syndrome
The development of potentially life-threatening serotonin syndrome has been reported with serotonin-norepinephrine reuptake inhibitors, including reboxetine alone, and with concomitant use of other serotonergic drugs (e.g., selective serotonin reuptake inhibitors, other SNRIs, triptans, tricyclic and tetracyclic antidepressants, lithium, opioids, tryptophan, buspirone, monoamine oxidase inhibitors, and St. John’s
Wort). If concomitant use of reboxetine with other serotonergic drugs is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.
As with all antidepressants, switches to mania/hypomania have occurred during the clinical studies. Close supervision of bipolar patients is, therefore, recommended.
Concomitant use of MAO-inhibitors (including linezolid (an antibiotic which is a reversible non-selective MAOI) and methylene blue) and reboxetine should be avoided in view of the potential risk (tyramine-like effect) based on their mechanisms of action.
Suicide/suicidal thoughts or clinical worsening
Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.
Orthostatic hypotension
Over the maximum recommended dose, orthostatic hypotension has been observed with greater frequency than that observed at recommended doses. Particular attention should be paid when administering reboxetine with other drugs known to lower blood pressure.
Mydriasis
Mydriasis has been reported in association with reboxetine; therefore, caution should be used when prescribing reboxetine to patients with increased intraocular pressure or those at risk of acute narrow-angle glaucoma.
Other
Close supervision should be applied in patients with current evidence of urinary retention, prostatic hypertrophy, glaucoma and history of cardiac disease.
See prescribing information for full details.

Very common: Insomnia, Dizziness, Dry mouth, Constipation, Nausea, and Hyperhidrosis.
Common: Decreased appetite, Agitation, Anxiety, Headache, Paraesthesia, Akathisia, Dysguesia, Accommodation disorder, Tachycardia, Palpitations, Vasodilatation, Hypotension, Hypertension, Vomiting, Rash, Sensation of incomplete bladder emptying, Urinary tract infection, Dysuria, Urinary retention, Erectile, dysfunction, Ejaculatory pain, Ejaculatory delay, Chills.
For full details see prescribing information.

Potent inhibitors of CYP3A4 (ketoconazole, nefazodone, erythromycin and fluvoxamine), would be expected to increase plasma concentrations of reboxetine.
CYP3A4 inducers (phenobarbital, carbamazepine, phenytoin, rifampicin and St John´s Wort) would be expected to decrease plasma concentrations of reboxetine.
Serotonergic medications Concomitant administration with any other medication which increases the amount of free serotonin in the synapse carries the risk of inducing serotonin syndrome. Medications to consider are those which inhibit reuptake of serotonin (SSRIs, SNRIs, tricyclics, and opioids); those which inhibit catabolism of serotonin (MAOIs, triptans, St John’s Wort); those which increase production of serotonin (L-tryptophan); those which release serotonin (opioids such as buprenorphine); those directly acting on serotonin receptors (triptans, lithium, opioids); and those working by other mechanisms (lithium, tricyclics, tetracyclics, and opioids). The most serious side effects and even death have been reported following the concomitant use of certain serotonergic medications with monoamine oxidase (MAO) inhibitors. Therefore, MAO inhibitors should be discontinued at least 2 weeks prior to the cautious initiation of therapy with reboxetine. The exact length of time may vary and is dependent upon the particular MAO inhibitor being used, the length of time it has been administered, and the dosage involved.
MAO-inhibitors (including linezolid an antibiotic which is a reversible non-selective MAOI and methylene blue) and reboxetine should be avoided in view of the potential risk (tyramine-like effect) based on their mechanisms of action.
Ergot derivatives and reboxetine might result in increased blood pressure.
See prescribing information for full details.

Pregnancy: No clinical trial data on exposure to reboxetine during pregnancy are available. However, postmarketing safety data on a very limited number of exposed pregnancies indicate no adverse effects of reboxetine on pregnancy or on the health of the fetus/newborn child. Animal studies in general do not indicate direct or indirect harmful effects with respect to pregnancy, embrynal/fetal development or parturition. Some impairment of growth and development has been noted in rat neonates. Reboxetine should only be used in pregnancy if the potential benefits of treatment to the mother outweigh the possible risks to the developing fetus.
Women of child-bearing potential: If conception occurs during therapy, treatment is to be discontinued as soon as pregnancy is confirmed to limit foetal exposure to the drug.
Lactation: Reboxetine is known to be excreted in breast milk. The level of active substance transferred in breast milk is anticipated to be very low, however there is insufficient information to exclude a risk to the nursing infant. The use of reboxetine during breastfeeding can be considered if the potential benefits outweigh the risk for the child.

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. Elderly might be particularly vulnerable to overdose. In premarketing clinical studies, there were 5 reports of reboxetine overdose alone or in combination with other pharmacologic agents. The amount of reboxetine ingested was 52 mg as the sole agent by 1 patient and 20 mg in combination with other agents by another patient. The remaining 3 patients ingested unknown quantities of reboxetine. All 5 patients recovered fully. There were no reports of ECG abnormalities, coma, or convulsions following overdose with reboxetine alone. In postmarketing experience, there have been few reports of overdose in patients taking reboxetine alone; none of these have proved fatal. Non-fatal overdoses in patients have been reported for patients taking up to 240 mg of reboxetine. One fatal overdose was reported in a patient who ingested reboxetine in combination with amitriptyline (doses unknown). 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. General symptomatic supportive and/or emetic measures might be required.