Fluvoxamine
Voxam
Category
Antiobsessional agent, antidepressant.
(USP DI)
Chemistry
Fluvoxamine Maleate.
C15H21F3N2O2'C4H4O4= 434.4.
(E)-5-Methoxy -4'-trifluoromethylvalerophenone O-2-aminothyloxime maleate.
Mechanism of action / Pharmacokinetics
The mechanism of action of fluvoxamine as an antiobsessional agent and as an antidepressant is presumed to be linked to its specific serotonin reuptake inhibition in brain neurons .Fluvoxamine potently and specifically inhibits presynaptic neuronal reuptake of 5-HT by blocking the membrane pump mechanism for neuronal 5-HT reuptake, thereby facilitating serotonergic transmission and decreasing 5-HT turnover.
(USP DI)
Pharmacokinetics properties
Time of peak plasma concentration (hrs) 3 - 8
Peak plasma concentration (ng/mL) 88 - 546
Half - life (hrs) 13.6 - 15.6
Protein binding (%) 80
Time to reach steady state (days) 7
Primary route of elimination %94 renal
Bioavailability (%) 53
(Facts)
Indications:
- Treatment of Obsessive – compulsive disorder. (OCD)
- Treatment of depressive disorder, major.
(USP DI)
Contraindication:
- Co- administration of alosetron, astemizole, cisapride, terfenadine, thioridazine or
pimozide with fluvoxamine contraindicated.
- Hypersensitivity to SSRIs or any inactive ingredients.
- In combination with a monoamine oxidase inhibitor (MAOI) or within 14 days of
discontinuing an MAOI.
(USPDI - Facts)
Warning and Precaution:
1- Antidepressants increased the risk of suicidal thinking and behavior in short - time studies in children and adolescents with major depressive disorder and other psychiatric disorders anyone considering the use of fluvoxamine or any other antidepressant in a child or adolescent must balance this risk with the clinical need.
(USP DI)
2- Because decreased appetite and weight loss are associated with fluvoxamine use,
monitoring of weight and growth parameters is recommended in children receiving long - term treatment with fluvoxamine.
(USP DI)
3- It is recommended that fluvoxamine should be withdrawn in patients who have increased serum liver enzyme concentration.
4- Fluvoxamine may need to be given with caution to patients with hepatic or renal
impairment and to the elderly.
(Martindale)
5- Seizures have occurred with fluvoxamine. Use with care in patients with history of
seizures; discontinue therapy if seizures occur.
(Facts)
6- Smokers had a 25% increase in the metabolism of fluvoxamine compared with
nonsmokers.
(Facts)
7- Fluvoxamine may impair judgment, thinking, or motor skills; caution patients about operating hazardous machinery, including automobiles, until they are reasonably certain that the drug treatment does not affect them adversely.
(Facts)
Pregnancy:
Category C.
Fluvoxamine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
(USP DI)
Breast Feeding:
Fluvoxamine is distributed into breast milk, but does not appear to accumulate in breast milk. Discontinue nursing or to discontinue the drug should take into account the potential for serious adverse effects from exposure to fluvoxamine in the nursing infant as well as the potential benefits of fluvoxamine maleate tablet therapy to the mother.
(USP DI)
Drug Interaction:
1- Fluvoxamine can greatly increase plasma concentration of theophylline and they should not be given together or if it is unavoidable the dose of theophylline should be halved and plasma theophylline concentration monitored more closely.
(Martindale)
2- Coadministration of fluvoxamine with amitriptyline, clompiramine, of imipramine has resulted in significantly increased plasma concentrations of the TACs.
(USP DI)
3- Fluvoxamineis likely to reduce the clearance of these benzodiazepines, concurrent use has been shown to reduce the clearance of alprazolam, bromazepin, diazepam by 50% or more, and to impair psychomotor performance and memory.
4- Significantly increased methadone plasma concentration to dose rations have been reported when fluvoxamine was added to the regimens of patients on methadone maintenance.
5- A serotonin syndrome (eg, CNS irritability, shivering, myoclonus, altered consciousness) may occur after coadministration fluvoxamine and metoclopramide, sibutramine and tramadol.
6- Tryptophan may enhance the serotonergic effects of fluvoxamine; use the combination with caution. Severe vomiting has been reported with the coadministration of fluvoxamine and tryptophan.
7- If propranolol or metoprolol is given with fluvoxamine, reduce the initial beta blocker dose.
8- Effects of buspirone may be decreased; plasma concentrations may be increased with fluvoxamine but clinical response may be decreased. Paradoxical worsening of OCD or serotonin syndrome has occurred.
9- Serum carbamazepine, haloperidol & mexiletine levels may be increased with
fluvoxamine, possibly resulting in toxicity.
10- Elevated serum clozapine levels have occurred. Closely monitor patients on concomitant administration with fluvoxamine, cyclosporine, hydantoin, tacrin, olanzapine & ropivacaine.
11- Bradycardia has occurred with concurrent use of fluvoxamine and ditiazem.
12- Lithium may enhance the serotonergic effects of fluvoxamine. Use with caution in combination; seizures have been reported.
13- The risk of GI adverse effects may be increased with the coadministration of fluvoxamine and NSAIDs. If possible, avoid concurrent use.
14- Fluvoxamine has been shown to decrease the clearance of tolbutamide. Fluvoxamine also has been shown to increase the peak plasma concentration of glimepiride.
15- Fluvoxamine increased warfarin plasma levels by 98%; PT was prolonged. Monitor PT. use caution with coadministration and monitor patient.
(Facts)
Adverse reaction:
Hypertension, hypertension (postural). palpitations, syncope, tachycardia, vasodilation, agitation, amnesia, anxiety, apathy, CNS stimulation, depersonalization, depression, dizziness, emotional lability, headache, hypertonia, hypo/hyperkinesia, insomnia, libido decreased, manic reaction, myoclonus/twitching, nervousness, psychotic reaction, sleep disorder, somnolence, tremor, vertigo, acne, sweating, excessive/increased, abdominal pain, anorexia, constipation, diarrhea/loose stools, dry mouth, dyspepsia, dysphagia, flatulence, gastroenteritis, nausea, tooth disorder/caries, vomiting, abnormal ejaculation, sexual dysfunction/impotence/anorgasmia, urinary frequency, urinary tract infection, urination disorder /retention, arthralgia, myasthenia, myopathy ,bronchitis ,cough (increased), dyspnea, sinusitis, upper respiratory tract infection, yawn, amblyopia, taste perversion/change ,accindental injury/trauma, allergy/allergic reaction, asthenia, chills, edema, flu syndrom, malaise, weight pain, weight loss.
(Facts)
Over dosage:
Diarrhea, dizziness, drowsiness, nausea, vomiting, bradycardia, coma, dryness of mouth, electrocardiogram abnormalities, mydriasis, seizures, tachycardia, tremor, urinary retention, hypotension, liver function abnormalities, myoclonus
(USP DI).
Administration and Dosage:
►Usual adult and geriatric dose:
Initially 50 mg in a single dose at bedtime. The doses may be increased as needed and tolerated increments of 50 mg a day at intervals of four to seven days. If the daily dosage exceed 100 mg it should be taken in two divided doses. If the doses are not equal the larger dose should be taken at bedtime.
►Usual adult prescribing limits
300 mg per day.
►Usual pediatric dose
Antiobsessional agent.
- Children younger than 8 years of age: safety and efficacy have not been established.
- Children 8 to 17 years of age: Oral initially 25 mg in a single dose at bedtime The dosage may be increased as needed and tolerant the daily dosage exceed 50 mg ,it should be administrated in the divided doses. If the doses are not equal the larger dose should be administrated at bedtime.
►Usual pediatric prescribing limits
Children 8 to 17 years of age: 200 mg a day.
(USP DI)
Storage:
Store below 30C. Protect from humidity and direct light.
(USP DI)
How supplied:
Voxam® 50 mg is supplied as pale yellow, round shape film coated tablets in blister of 10`s in boxes of 30`s.
Voxam® 100 mg is supplied as white, oval shape film coated tablets in blister of 10`s in boxes of 30`s.
References:
1- USP DI 2007.
2- PDR 2010.
3- Martindale 36.
4- Drug Facts 2009.