Fluvoxamine Film Coated Tablets
Fluvoxamine maleate 50 mg/Film Coated Tablet
Company Name
Alexandria
Therapeutic Group
SSRI ANTIDEPRESSANTS
Pharmaceutical form
Tablets
Package
1,2 or 3 strips(Al/PVDC) X 10 tablets (local market) & 100 strips(Al/PVDC) X 10 tablets (export)
Indications
"Major depressive episode
Obsessive Compulsive Disorder (OCD)
Warning & Precautions
"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. Other psychiatric conditions for which Fluvoxamine is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders. Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old. Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present. Paediatric population Fluvoxamine should not be used in the treatment of children and adolescents under the age of 18 years, except for patients with Obsessive Compulsive Disorder. 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. Geriatric population Data in elderly subjects give no indication of clinically significant differences in normal daily dosages compared to younger subjects. However, upward dose titration should be done slower in the elderly, and dosing should always be done with caution. Renal and hepatic impairment Patients suffering from hepatic or renal insufficiency should start on a low dose and be carefully monitored. Treatment with fluvoxamine has rarely been associated with an increase in hepatic enzymes, generally accompanied by clinical symptoms. In such cases treatment should be discontinued.
Product Type
Human
Dosage
"Depression
Adults
The recommended dose is 100 mg daily. Patients should start on 50 or 100 mg, given as a single dose in the evening. Dosage should be reviewed and adjusted if necessary within 3 to 4 weeks of initiation of therapy and thereafter as judged clinically appropriate. Although there may be an increased potential for undesirable effects at higher doses, if after some weeks on the recommended dose insufficient response is seen some patients may benefit from having their dose increased gradually up to a maximum of 300 mg a day. Doses up to 150 mg can be given as a single dose, preferably in the evening. It is advisable that a total daily dose of more than 150 mg is given in 2 or 3 divided doses. Dosage adjustments should be made carefully on an individual patient basis, to maintain the patients at the lowest effective dose. Patients with depression should be treated for a sufficient period of at least six months to ensure that they are free from symptoms.
Children/adolescents
Fluvoxamine should not be used in children and adolescents under the age of 18 years for the treatment of major depressive episode. The efficacy and safety of Fluvoxamine have not been established in the treatment of paediatric major depressive episode
Obsessive Compulsive Disorder
Adults
The recommended dose is between 100-300 mg daily. Patients should start at 50 mg per day. Although there may be an increased potential for undesirable effects at higher doses, if after some weeks on the recommended dose insufficient response is seen some patients may benefit from having their dose increased gradually up to a maximum of 300 mg a day. Doses up to 150 mg can be given as a single dose, preferably in the evening. It is advisable that a total daily dose of more than 150 mg is given in 2 or 3 divided doses. If a good therapeutic response has been obtained, treatment can be continued at a dosage adjusted on an individual basis. While there are no systematic studies to answer the question of how long to continue fluvoxamine treatment, OCD is a chronic condition and it is reasonable to consider continuation beyond 10 weeks in responding patients. Dosage adjustments should be made carefully on an individual patient basis, to maintain the patients at the lowest effective dose. The need for treatment should be reassessed periodically. Some clinicians advocate concomitant behavioural psychotherapy for patients who have done well on pharmacotherapy. Long-term efficacy (more than 24 weeks) has not been demonstrated in OCD.
Children/adolescents
In children over 8 years and adolescents there is limited data on a dose of up to 100 mg b.i.d for 10 weeks. The starting dose is 25 mg per day. Increase every 4-7 days in 25 mg increments as tolerated until an effective dose is achieved. The maximum dose in children should not exceed 200 mg/day. It is advisable that a total daily dose of more than 50 mg should be given in two divided doses. If the two divided doses are not equal, the larger dose should be given at bedtime.
Withdrawal symptoms seen on discontinuation of fluvoxamine
Abrupt discontinuation should be avoided. When stopping treatment with fluvoxamine the dose should be gradually reduced over a period of at least one or two weeks in order to reduce the risk of withdrawal reactions. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate.
Hepatic or renal insufficiency
Patients suffering from hepatic or renal insufficiency should start on a low dose and be carefully monitored.
Fluvoxamine tablets should be swallowed with water and without chewing
Adverse Reactions
"Side effects have been reported spontaneously during postmarketing use of fluvoxamine. A precise frequency cannot be provided and is therefore classified as 'not known'.
Blood and lymphatic system disorders: Haemorrhage (e.g. gastrointestinal haemorrhage, ecchymosis, purpura).
Endocrine disorders: Inappropriate antidiuretic hormone secretion.
Metabolism and nutrition disorders: Hyponatraemia, weight increased, weight decreased.
Nervous system disorders: Serotonin syndrome, neuroleptic malignant syndrome-like events, paresthesia, dysgeusia, and SIADH have been reported.
Renal and urinary disorders: micturition disorder (including urinary retention, urinary incontinence, pollakiura, nocturia and enuresis)
Reproductive system and breast disorders: Anorgasmia.
General disorders and administration site conditions: drug withdrawal syndrome including drug withdrawal syndrome neonatal .Psychomotor restlessness/akathisia.
Cases of suicidal ideation and suicidal behaviours have been reported during fluvoxamine therapy or early after treatment discontinuation (see section 4.4 Special warnings and precautions for use).
Withdrawal symptoms seen on discontinuation of fluvoxamine treatment
Discontinuation of fluvoxamine (particularly when abrupt) commonly leads to withdrawal symptoms. Dizziness, sensory disturbance (including paraesthesia, visual disturbance and electric shock sensations), sleep disturbances (including insomnia and intense dreams), agitation and anxiety, irritability, confusion, emotional instability, nausea and/or vomiting, diarrhoea, sweating, palpitations, headache and tremor are the most commonly reported reactions. Generally these events are mild to moderate and are self-limiting, however, in some patients they may be severe and/or prolonged. It is therefore advised that when fluvoxamine treatment is no longer required, gradual discontinuation by dose tapering should be carried out.
Class effects: Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving Selective Serotonin Reuptake Inhibitors (SSRIs) and Tricyclic Antidepressants (TCAs). The mechanism leading to this risk is unknown
Contra Indications
"Fluvoxamine tablets are contraindicated in combination with tizanidine and monoamine oxidase inhibitors (MAOIs).
Treatment with fluvoxamine can be initiated:
two weeks after discontinuation of an irreversible MAOI, or
the following day after discontinuation of a reversible MAOI (e.g. moclobemide).
At least one week should elapse between discontinuation of fluvoxamine and initiation of therapy with any MAOI.
Hypersensitivity to the active substance or to any of the excipients.
Drug Interactions
"Fluvoxamine should not be used in combination with MAOIs. Fluvoxamine is a potent inhibitor of CYP1A2, and to a lesser extent of CYP2C and CYP3A4. Drugs which are largely metabolised via these isoenzymes are eliminated slower and may have higher plasma concentrations when co-administered with fluvoxamine. This is particularly relevant for drugs with a narrow therapeutic index. Patients should be carefully monitored and, if necessary, dose adjustment of these drugs is recommended. Fluvoxamine has marginal inhibitory effects on CYP2D6 and seems not to affect non-oxidative metabolism or renal excretion.
CYP1A2 : An increase in previously stable plasma levels of those tricyclic antidepressants (e.g. clomipramine, imipramine, amitriptyline) and neuroleptics (e.g. clozapine and olanzapine) which are largely metabolised through cytochrome P450 1A2 when given together with fluvoxamine, has been reported. A decrease in the dose of these products should be considered if treatment with fluvoxamine is initiated. Patients co-administered fluvoxamine and CYP1A2 metabolised drugs with a narrow therapeutic index (such as tacrine, theophylline, methadone, mexiletine) should be carefully monitored and, if necessary, dose adjustment of these drugs is recommended. Isolated cases of cardiac toxicity have been reported when fluvoxamine was combined with thioridazine. As plasma concentrations of propranolol are increased in combination with fluvoxamine, the propranolol dose may need to be lowered. Caffeine plasma levels are likely to be increased during co-administration with fluvoxamine. Thus, patients who consume high quantities of caffeine-containing beverages should lower their intake when fluvoxamine is administered and adverse caffeine effects (like tremor, palpitations, nausea, restlessness, insomnia) are observed. As plasma concentrations of ropinirole may be increased in combination with fluvoxamine thus increasing the risk of overdose, surveillance and reduction in the dosage of ropinirole during fluvoxamine treatment and after its withdrawal may be required.
CYP2C : Patients co-administered fluvoxamine and CYP2C metabolised drugs with a narrow therapeutic index (such as phenytoin) should be carefully monitored and, if necessary, dose adjustment of these drugs is recommended.
Warfarin: When given with fluvoxamine, warfarin plasma concentrations were significantly increased and prothrombin times prolonged. The cytochrome P-450 isozymes involved in the metabolism of warfarin include 2C9, 2C19, 2C8, 2C18, 1A2, and 3A4. 2C9 is likely to be the principal form of human liver P-450 which modulates the in vivo anticoagulant activity of warfarin.
CYP3A4 :Terfenadine, astemizole, cisapride (see also section 4.4 Special Warnings and Precautions for Use). Patients co-administered fluvoxamine and CYP3A4 metabolised drugs with a narrow therapeutic index (such as carbamazepine and ciclosporin) should be carefully monitored and, if necessary, dose adjustment of these drugs is recommended. The plasma levels of oxidatively metabolised benzodiazepines (e.g. triazolam, midazolam, alprazolam, and diazepam) are likely to be increased when co-administered with fluvoxamine. The dosage of these benzodiazepines should be reduced during co-administration with fluvoxamine.
Glucuronidation :Fluvoxamine does not influence plasma concentrations of digoxin.
Renal excretion : Fluvoxamine does not influence plasma concentrations of atenolol.
Pharmacodynamic interactions
The serotonergic effects of fluvoxamine may be enhanced when used in combination with other serotonergic agents (including triptans, SSRIs and St. John´s Wort preparations). Fluvoxamine has been used in combination with lithium in the treatment of severely ill, drug-resistant patients. However, lithium (and possibly also tryptophan) enhances the serotonergic effects of fluvoxamine. The combination should be used with caution in patients with severe, drug-resistant depression. In patients on oral anticoagulants and fluvoxamine, the risk for haemorrhage may increase and these patients should therefore be closely monitored. As with other psychotropic drugs, patients should be advised to avoid alcohol use while taking fluvoxamine
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