For fluoxetine a washout period of two to three weeks is advised before and after treatment with fluoxetine.Tricyclic antidepressants are known to lower the convulsion threshold and clomipramine should therefore, be used with extreme caution in patients with epilepsy and other predisposing factors, Concomitant treatment of clomipramine and electroconvulsive therapy should only be resorted to under careful supervision.Because of its anticholinergic properties, clomipramine should be used with caution in patients with a history of increased intra-ocular pressure, narrow-angle glaucoma, urinary retention or with symptoms of bladder neck obstruction, Decreased lacrimation and accumulation of mucoid secretions due to the anticholinergic properties of tricyclic antidepressants may cause damage to the corneal epithelium in patients with contact lenses.Caution is called for when giving tricyclic antidepressants to patients with severe hepatic disease and tumours of the adrenal medulla (Caution is advised in patients with hyperthyroidism or during concomitant treatment with thyroid preparations since aggravation of unwanted cardiac effects may occur.It is advisable to monitor cardiac and hepatic function during long-term therapy with clomipramine. • Do not drive until you know how the medicine affects you It is taken by mouth. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.Do not give clomipramine for at least 3 weeks after discontinuation of treatment with MAO inhibitors (there is a risk of severe symptoms consistent with Serotonin Syndrome such as hypertensive crisis, hyperpyrexia, myoclonus, agitation, seizures, delirium and coma). This risk persists until significant remission occurs. Staggering the dosage of clomipramine and resins, such that the drug is administered at least 2 h before or 4-6 h after the administration of resins, is recommended.Concomitant administration of clomipramine with St. John's wort during the treatment may decrease the plasma concentrations of clomipramine.Tricyclic antidepressants may potentiate the effects of these drugs (Clomipramine may diminish or abolish the antihypertensive effects of guanethidine, betanidine, reserpine, clonidine and alpha-methyldopa.
These disappear within a few days of withdrawing the drug.As improvement in depression may not occur for the first two to four weeks treatment, patients should be closely monitored during this period.Elderly patients are particularly liable to experience adverse effects, especially agitation, confusion, and postural hypotension.Clomipramine should be administered with particular precaution in patients with cardiovascular disorders, especially those with cardiovascular insufficiency, conduction disorders, (There may be a risk of QTc prolongation and torsades de pointes, particularly at supra-therapeutic doses or supra-therapeutic plasma concentrations of clomipramine, as occur in the case of co- medication with selective serotonin reuptake inhibitors (SSRIs).
Hypokalaemia should therefore be treated prior to administration of clomipramine (see sections 4.2 and 4.4).Tricyclic antidepressants should not be employed in combination with antiarrhythmic agents of the quinidine type.SSRIs which are inhibitors of CYP2D6, such as fluoxetine, paroxetine, or sertraline, and of others including CYP1A2 and CYP2C19 (Serotonin Syndrome can possibly occur when clomipramine is administered with other serotonergic co-medications such as selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenergic reuptake inhibitors (SNaRIs), tricyclic antidepressants and lithium (see sections 4.2 and 4.4). Antipsychotic agents may increase the plasma concentration of tricyclic agents. Clomipramine is metabolised by cytochrome P450 2D6 and the plasma concentration of clomipramine may therefore be increased by drugs that are either substrates and/or inhibitors of this P450 isoform. Examples of drugs which are substrates or inhibitors of cytochrome P450 2D6 include antiarrhythmics, certain antidepressants including SSRIs, tricyclic antidepressants and moclobemide; certain antipsychotics; β-blockers; protease inhibitors, opiates, ecstasy (MDMA), cimetidine and terbinafine.
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