Fluvoxamine Maleate

Pronunciation

Pronunciation: floo-VOX-a-meen MAL-ee-ate
Class: SSRI

Trade Names

Luvox
- Tablets 25 mg
- Tablets 50 mg
- Tablets 100 mg
- Capsules, extended-release 100 mg
- Capsules, extended-release 150 mg

Apo-Fluvoxamine (Canada)
CO Fluvoxamine (Canada)
Luvox (Canada)
PMS-Fluvoxamine (Canada)
ratio-Fluvoxamine (Canada)
Sandoz Fluvoxamine (Canada)

Pharmacology

Inhibits neuronal reuptake of serotonin in the brain.

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Pharmacokinetics

Absorption

Absolute bioavailability is 53%. At steady state, T max is 3 to 8 h and C max is 88 to 546 ng/mL.

Extended-release

Bioavailability is 84% and mean C max is 38% lower compared with immediate-release tablets. A 3-fold increase in dose results in a 5.7- and 3-fold increase in AUC and C max , respectively, indicating nonlinear pharmacokinetics.

Distribution

Mean apparent Vd is about 25 L/kg. Fluvoxamine is about 80% protein bound.

Metabolism

Extensively metabolized by the liver. The main routes are oxidative demethylation and deamination of 9 metabolites; the major metabolite is fluvoxamine acid.

Elimination

About 2% is excreted unchanged in the urine. Mean t ½ is 15.6 h at steady state.

Extended-release

Mean plasma t ½ is 16.3 h.

Special Populations

Hepatic Function Impairment

30% decrease in Cl.

Elderly

Cl is reduced by 50% and mean max plasma concentrations are 40% higher.

Children

For the immediate-release tablets, AUC and C max were 1.5- and 2.7-fold higher, respectively, in children 6 to 11 yr of age. Female children had significantly higher AUC and C max compared with males. AUC and C max in adolescents 12 to 17 yr of age were similar to adults and there were no gender differences.

Gender

The AUC and C max were increased by approximately 60% in healthy women compared with men. The t ½ was not different between men and women.

Indications and Usage

Immediate-release tablets

Obsessive-compulsive disorder.

Extended-release capsules

Obsessive-compulsive disorder; social anxiety disorder, also known as social phobia.

Unlabeled Uses

Bulimia nervosa; depression; panic disorder; nocturnal enuresis.

Contraindications

Coadministration of alosetron, cisapride, MAOIs, pimozide, thioridazine, or tizanidine; hypersensitivity to any component of the product.

Dosage and Administration

Obsessive-compulsive disorder
Adults Extended-release

PO 100 mg once daily as a single dose at bedtime. The dose may be increased in 50 mg increments every 7 days, as tolerated, until max therapeutic benefit is achieved (max, 300 mg/day). Adjust dose to maintain the patient on the lowest effective dosage. Periodically reassess patients to determine the need for continued treatment.

Immediate-release

PO 50 mg as a single dose at bedtime initially.

Usual range

100 to 300 mg/day. Increase dose in 50 mg increments every 4 to 7 days, as tolerated, until max therapeutic benefit is achieved (max, 300 mg/day). Give total daily doses of more than 100 mg in 2 divided doses; if doses are unequal, give larger dose at bedtime.

Maintenance

Dosage is adjusted to maintain patient on lowest effective dosage. Periodically reassess need to continue treatment.

Children 8 to 17 yr of age Immediate-release

PO Start with 25 mg as a single daily dose at bedtime.

Usual range

50 to 200 mg/day. Increase dose in 25 mg increments every 4 to 7 days, as tolerated, until max therapeutic benefit is achieved (max, 200 mg/day for children 8 to 11 yr of age and 300 mg/day for children 12 to 17 yr of age). Give total daily doses of more than 50 mg in 2 divided doses; if doses are unequal, give larger dose at bedtime.

Social Anxiety Disorder
Adults Extended-release

PO 100 mg once daily as a single dose at bedtime. The dose may be increased in 50 mg increments every 7 days, as tolerated, until max therapeutic benefit is achieved (max, 300 mg/day).

General Advice

  • Administer without regard to meals; administer with food if GI upset occurs.
  • Extended-release capsules should be swallowed whole; do not break, crush, or chew.

Storage/Stability

Immediate-release tablets

Store at 68° to 77°F. Protect from high humidity. Dispense in a tightly closed, light-resistant container.

Extended-release capsules

Store at 59° to 86°F. Protect from high humidity. Avoid exposure to temperatures above 86°F.

Drug Interactions

Alosetron, cisapride, MAOIs, pimozide, thioridazine, tizanidine

Coadministration with fluvoxamine is contraindicated.

Aspirin, heparin, NSAIDs, warfarin

Risk of bleeding may be increased.

Benzodiazepines (eg, alprazolam, diazepam, midazolam, triazolam), carbamazepine, clozapine, lidocaine, methadone, metoprolol, mexiletine, phenytoin, phosphodiesterase type 5 inhibitors (eg, sildenafil), propranolol, proton pump inhibitors, quinidine, ropivacaine, tacrine, theophylline, tricyclic antidepressants

Plasma levels of these drugs may be increased.

Cyproheptadine

Pharmacologic effects of fluvoxamine may be decreased.

Grapefruit

Fluvoxamine plasma levels may be elevated.

Diltiazem

Bradycardia may occur.

MAOIs

Similar SSRIs can cause serious (sometimes fatal) reactions. Do not give fluvoxamine in combination with MAOIs or within 14 days of discontinuation of MAOIs. After stopping fluvoxamine, wait at least 2 wk before starting MAOIs.

Ramelteon

Ramelteon plasma levels may be greatly elevated, increasing the risk of adverse reactions. Do not coadminister with fluvoxamine.

Serotonergic drugs (eg, 5-HT 1 agonists, linezolid, lithium, St. John's wort, tramadol), sympathomimetics, tryptophan

Risk of serotonin syndrome may be increased.

Smoking

Increases metabolism of fluvoxamine.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Immediate-release tablets

Palpitations, vasodilation (3%); hypertension, hypotension, syncope, tachycardia (at least 1%); ventricular tachycardia, including torsades de pointes (postmarketing).

Extended-release capsules

Palpitation (3%); hypertension, vasodilation (2%).

CNS

Immediate-release tablets

Headache, somnolence (22%); insomnia (21%); asthenia (14%); nervousness (12%); dizziness (11%); anxiety, tremor (5%); agitation, decreased libido, depression, hypertonia, stimulation (2%); amnesia, apathy, hyperkinesia, hypokinesia, malaise, manic reaction, psychotic reaction (at least 1%); myoclonus neuropathy, serotonin syndrome (postmarketing).

Extended-release capsules

Headache, insomnia (35%); somnolence (27%); asthenia (26%); dizziness (15%); dry mouth (11%); nervousness (10%); anxiety, tremor (8%); decreased libido (6%); abnormal dreams, abnormal thinking, agitation, apathy, paresthesia (3%); hypertonia, neurosis, twitching (2%).

Dermatologic

Immediate-release tablets

Sweating (7%); bullous eruption, Henoch-Schönlein purpura, Stevens-Johnson syndrome, toxic epidermal necrolysis (postmarketing).

Extended-release capsules

Sweating (7%); acne (2%).

EENT

Immediate-release tablets

Amblyopia, taste perversion (3%); laryngismus (postmarketing).

Extended-release capsules

Pharyngitis (6%); laryngitis (3%); amblyopia, epistaxis (2%).

GI

Immediate-release tablets

Nausea (40%); dry mouth (14%); diarrhea (11%); constipation, dyspepsia (10%); anorexia (6%); vomiting (5%); flatulence (4%); tooth disorder (3%); dysphagia (2%); abdominal pain (1%); ileus, pancreatitis (postmarketing).

Extended-release capsules

Nausea (39%); diarrhea (18%); anorexia (14%); dyspepsia (10%); constipation, vomiting (6%); abdominal pain (5%); gingivitis, taste perversion, tooth disorder (2%).

Genitourinary

Immediate-release tablets

Abnormal ejaculation (8%); urinary frequency (3%); anorgasmia, impotence (2%); urinary retention (1%); acute renal failure, priapism (postmarketing).

Extended-release capsules

Abnormal ejaculation (11%); anorgasmia (5%); abnormal sexual function, menorrhagia (3%); impotence, polyuria, UTI (2%).

Hematologic-Lymphatic

Immediate-release tablets

Agranulocytosis, aplastic anemia (postmarketing).

Extended-release capsules

Ecchymosis (4%).

Hepatic

Immediate-release tablets

Hepatitis (postmarketing).

Extended-release capsules

Abnormal LFTs (2%).

Hypersensitivity

Immediate-release tablets

Anaphylactic reaction, angioedema (postmarketing).

Lab Tests

Immediate-release tablets

Elevated liver transaminases (at least 1%).

Metabolic-Nutritional

Immediate-release tablets

Edema, weight gain, weight loss (at least 1%); hyponatremia (postmarketing).

Extended-release capsules

Weight loss (2%).

Musculoskeletal

Extended-release capsules

Myalgia (5%).

Respiratory

Immediate-release tablets

Upper respiratory tract infection (9%); dyspnea, yawn (2%); increased cough, sinusitis (at least 1%).

Extended-release capsules

Yawning (5%); bronchitis (2%).

Miscellaneous

Immediate-release tablets

Flu-like syndrome (3%); chills (2%); accidental injury (at least 1%); porphyria, vasculitis (postmarketing).

Extended-release capsules

Pain (10%); accidental injury (5%); chest pain (3%); viral infection (2%).

Precautions

Warnings

Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorders and other psychiatric disorders. Appropriately monitor patients of all ages who are started on antidepressant therapy and closely observe for clinical worsening, suicidality, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the prescriber.


Monitor

Frequently assess patient for response to treatment. Periodically review therapy to determine if a dose change is indicated.


Pregnancy

Category C .

Lactation

Excreted in breast milk.

Children

Immediate-release tablets

Safety and efficacy not established for children younger than 8 yr of age.

Extended-release capsules

Safety and efficacy not established.

Elderly

Because of decreased drug Cl, titrate the dosage slowly after the initial dose.

Hepatic Function

Because of decreased drug Cl, titrate the dosage slowly after the initial dose

Abnormal bleeding

Bleeding episodes can occur in patients treated with drugs that interfere with serotonin reuptake.

Bipolar disorder

Screen for bipolar disorder prior to initiating therapy.

Cognitive and motor performance

Caution patients in operating potentially hazardous machinery (eg, cars) until they know whether the drug impairs their ability. Advise patients to avoid use of alcohol.

Concomitant illness

Caution is advised in patients with diseases or conditions that could affect hemodynamic responses or metabolism (eg, liver dysfunction).

Discontinuation

When discontinuing or reducing dose, gradually decrease dose and monitor the patient for adverse reactions (eg, abnormal skin sensations, agitation, anxiety, confusion, dizziness, dysphoric mood, irritability, nausea, sweating). If intolerable symptoms occur, consider reinstating therapy at previous dose and attempt to decrease dose at a more gradual rate.

Hyponatremia

Hyponatremia and SIADH have been reported and appear to be reversible when fluvoxamine is discontinued.

Mania/Hypomania

Fluvoxamine may activate hypomania or mania. Use cautiously in patients with history of mania.

Neuroleptic malignant syndrome

Has occurred and is potentially fatal. Signs and symptoms include altered mental status, diaphoresis, hyperpyrexia, irregular BP, irregular pulse, muscle rigidity, or tachycardia.

Seizures

Use with caution in patients with history of seizures. Seizures have been reported in small numbers of patients given this drug.

Serotonin syndrome

Life-threatening serotonin syndrome may occur, particularly with coadministration of serotonergic drugs.

Suicide

Supervise depressed patients at risk during initial therapy. Prescribe the smallest quantity consistent with good patient management to reduce the risk of overdose.

Overdosage

Symptoms

Bradycardia, coma, diarrhea, ECG abnormalities, hypokalemia, hypotension, increased reflexes, nausea, respiratory difficulties, seizures, somnolence, tachycardia, tremor, vomiting.

Patient Information

  • Advise patient to read patient information leaflet before starting therapy and with each refill.
  • Advise patient that medication is usually started at a low dose and then gradually increased until max benefit is obtained.
  • Advise patient taking once-daily dose to take at bedtime.
  • Advise patient to take prescribed dose without regard to meals, but to take with food if stomach upset occurs.
  • Inform patient that it may take 1 to 4 wk to note improvement in symptoms and to continue with prescribed therapy once improvement has been noted.
  • Instruct patient to contact health care provider if symptoms do not appear to be getting better or are getting worse, or if bothersome adverse reactions (eg, changes in sexual function, diarrhea, drowsiness, headache, insomnia, nausea, nervousness, unusual sweating) occur.
  • Advise patient to take frequent sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
  • Instruct patient to avoid alcoholic beverages and other depressants while taking this medication.
  • Advise patient that drug may impair judgment, thinking, or reflexes, and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
  • Advise patients and family to be alert for the emergence of agitation, irritability, and unusual changes in behavior as well as the emergence of suicidality, and to report such symptoms immediately to health care provider.

Copyright © 2009 Wolters Kluwer Health.

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