Dosing and uses of Faverin, Luvox (fluvoxamine)
Adult dosage forms and strengths
tablets
- 25mg
- 50mg
- 100mg
capsule, extended-release
- 100mg
- 150mg
Obsessive-Compulsive Disorder
Conventional tablets
- 50 mg qHS initially; may increase by 50 mg/day q4-7Days up to 100-300 mg/day
- Dose >100 mg/day should be divided q12hr
Extended-release capsules
- 100 mg PO qDay initially; may titrate in 50 mg/day increments every week
- Not to exceed 300 mg/day
Social Phobia (Off-label)
Immediate release
- 50 mg PO qDay; may increase by 50 mg at 1 week interval; usual dose range is 100-300 mg/day
Extended-release capsules
- 100 mg PO qDay initially; may titrate in 50 mg/day increments qWeek
- Not to exceed 300 mg/day
Panic Disorder (Off-label)
50 mg PO qDay; after several days, gradually increase to 150 mg/day; may increase to 300 mg/day for patients who fail to respond after several weeks of treatment
Dosing considerations
- Continue therapy for 1-2 years, and consider discontinuation with close supervision; when discontinuing therapy, a slow taper over 2-6 months is recommended
Posttraumatic Stress Disorder (Off-label)
50 mg/day PO initially; may increase dose to 100-250 mg in adults and 100 mg in older adults; not to exceed 300 mg/day
Dosing considerations
- Patients who respond to therapy may need to continue therapy indefinitely
- May attempt tapering after 6-12 months in patients with acute PTSD; tapering should occur gradually over 2 weeks to 1 month to avoid withdrawal symptoms; tapering should take place over 4-12 weeks in patients at risk of relapse
Dosing Modifications
Hepatic impairment: Decrease dose
Administration
May be administered with food
Pediatric dosage forms and strengths
tablet
- 25mg
- 50mg
- 100mg
capsule, extended-release
- 100mg
- 150mg
Obsessive-Compulsive Disorder
<8 years: Safety and efficacy not established
Ages 8-17 years (conventional tablets): 25 mg PO qHS initially; may titrate by 25 mg/day increments every 4-7 days to 50-200 mg/day
Not to exceed 200 mg (for ages 8-11 years) or 300 mg for adolescents
Give doses >50 mg/day divided q12hr
Geriatric dosage forms and strengths
The elderly are prone to SSRI/SNRI-induced hyponatremia; monitor closely
Obsessive-Compulsive Disorder
Conventional tablets: 25 mg qHS initially; may increase by 50 mg/day q4-7days up to 100-300 mg/day; dose >100 mg/day should be divided q12hr
Extended-release capsules: 100 mg PO qDay initially; may titrate in 50 mg/day increments every week; not to exceed 300 mg/day
Social Phobia
Extended-release capsules: 100 mg PO qDay initially; may titrate in 50 mg/day increments qWeek; not to exceed 300 mg/day
Faverin, Luvox (fluvoxamine) adverse (side) effects
>10%
Nausea (40%)
Headache (22-35%)
Somnolence (22-27%)
Weakness (14-26%)
Insomnia (20-35%)
Diarrhea (11-18%)
Dizziness (11-15%)
Xerostomia (10-14%)
Anorexia (6-14%)
Abnormal ejaculation (8-11%)
1-10%
Pain (10%)
Dyspepsia (8-10%)
Constipation (4-10%)
Decreased libido (2-10%)
Upper respiratory infections (9%)
Anxiety (5-8%)
Tremor (5-8%)
Sweating (6-7%)
Vomiting (4-6%)
Abdominal pain (5%)
Myalgia (5%)
Abnormal taste (2-5%)
Bruising (4%)
Abnormal dreams (3%)
Abnormal thinking (3%)
Chest pain (3%)
Palpitation (3%)
Agitation (2-3%)
Vasodilation (2-3%)
Hypertension (1-2%)
Increased LFTs (1-2%)
Weight change (1-2%)
Manic reaction
<1%
Activation of mania/hypomania, seizures (discontinue)
Sinusitis
Frequency not defined
Edema
Amnesia
Apathy
Asthenia
Malaise
Nervousness
Dry mouth
Myoclonus
Cough
Warnings
Black box warnings
In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses
This increase was not seen in patients aged >24 years; a slight decrease in suicidal thinking was seen in adults >65 years
In children and young adults, risks must be weighed against the benefits of taking antidepressants
Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during initial 1-2 months of therapy and dosage adjustments
The patient’s family should communicate any abrupt changes in behavior to the healthcare provider
Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy
This drug is not approved for use in pediatric patients
Contraindications
Hypersensitivity
Coadministration with serotonergic drugs
- Concomitant use or within 14 days of MAOIs increases risk of serotonin syndrome
- Reactions to concomitant administration with MAOIs include tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome, seizures, rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes (including extreme agitation progressing to delirium and coma)
- Starting fluvoxamine in a patient who is being treated with linezolid or IV methylene blue is contraindicated because of an increased risk of serotonin syndrome
- If linezolid or IV methylene blue must be administered, discontinue SSRI immediately and monitor for CNS toxicity; may resume 24 hr after last linezolid or methylene blue dose, or after 2 weeks of monitoring (5 weeks for fluoxetine), whichever comes first
Cautions
Conflicting evidence regarding use of SSRIs during pregnancy and increased risk of persistent pulmonary hypertension of the newborn (see Pregnancy)
In neonates exposed to SNRIs/SSRIs late in third trimester: Risk of complications such as feeding difficulties, irritability, and respiratory problems
Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy
May need to modify dose for hepatic impairment; titrate at smaller increments and longer intervals
Clinical worsening and suicide ideation may occur despite medication in adolescents and young adults (18-24 years)
May worsen mania symptoms or precipitate mania in patients with bipolar disorder
Increases risk of bleeding in patients taking anticoagulants/antiplatelets concomitantly
Do not use concurrently with alosetron, astemizole, cisapride, pimozide, terfenadine, or tizanidine due to QT prolongation risk
Potentially life-threatening serotonin syndrome reported when coadministered with drugs that impair serotonin metabolism (in particular, MAOIs, including nonpsychiatric MAOIs, such as linezolid and IV methylene blue) (see Contraindications)
May impair ability to operate heavy machinery and other tasks requiring mental alertness
Bone fractures have been associated with antidepressant treatment; consider possibility of fragility fracture if patient presents with pain, joint tenderness, or swelling
Impaired glucose control (hyperglycemia or hypoglycemia) reported; monitor for signs/symptoms of loss of glucose control, especially in patients with diabetes
May cause or exacerbate sexual dysfunction
Syndrome of inapropriate antidiuretic hormone and hyponatremia reported with SSRI and SNRI use; volume deplretion and/or concurrent use of diuretics may increase risk; consider discontinuing therapy if symptomatic hyponatremia occurs
Use caution in patients with cardiovascular disease or history of seizure disorder
Pregnancy and lactation
Pregnancy
Category: C
Use late in the third trimester associated with complications in newborns and may require prolonged hospitalization, respiratory support, and tube feeding
Persistent pulmonary hypertension of the newborn
- Potential risk of persistent pulmonary hypertension of the newborn when used during pregnancy
- Initial Public Health Advisory in 2006 was based on a single published study; since then, there have been conflicting findings from new studies, making it unclear whether use of SSRIs during pregnancy can cause PPHN
- FDA has reviewed the additional new study results and has concluded that, given the conflicting results from different studies, it is premature to reach any conclusion about a possible link between SSRI use in pregnancy and PPHN
- FDA recommendation: FDA advises healthcare professionals not to alter their current clinical practice of treating depression during pregnancy and to report any adverse events to the FDA MedWatch program
- A meta-analysis of 7 observational studies, found exposure to SSRIs in late pregnancy (ie, >20 weeks' gestation) more than doubled the risk of PPHN that could not be explained by other etiologies (eg, congenital malformations, meconium aspiration) (BMJ 2014;348:f6932)
Lactation
Present in breast milk; avoid
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Faverin, Luvox (fluvoxamine)
Mechanism of action
Selective serotonin reuptake inhibitor; little or no affinity for dopamine, alpha-adrenergic histamine, or cholinergic receptor
Absorption
Bioavailability: 53%
Peak plasma time: 3-8 hr
Peak plasma concentration: 88-546 ng/mL (nonlinear)
Distribution
Protein bound: 80%
Vd: 25 L/kg
Metabolism
Metabolism: Hepatic oxidative demethylation, deamination
Metabolites: Inactive
Enzymes inhibited: Hepatic CYP1A2, CYP2C9, CYP3A4
Elimination
Half-life: 15.6 hr; 17.4-25.9 hr (elderly)
Dialyzable: No
Excretion: Urine (85%)
Pharmacogenomics
Several SSRIs (eg, fluoxetine, fluvoxamine, paroxetine, sertraline) are metabolized by CYP2D6
CYP2D6 is involved in the metabolism of approximately 20% of drugs in clinical use and displays large individual-to-individual variability in activity due to genetic polymorphisms
More than 80 CYP2D6 variant alleles have been identified; however, 4 of the most prevalent alleles, CYP2D6*3, *4, *5, and *6, account for 93-97% of CYP2D6 poor metabolizers (PMs)
CYP2D6*4, the most common variant (~25% frequency in whites), causes a splicing defect; CYP2D6*3 (2.7% frequency) causes a frameshift mutation; and CYP3D6*5 (2.6%) is an entire deletion of the CYP2D6 gene; individuals homozygous for these alleles have no CYP2D6 activity
The impact of CYP2D6 activity is further complicated in some SSRIs (eg, fluoxetine, fluvoxamine, paroxetine, sertraline) that, in addition to being substrates for CYP2D6, are also known to moderately inhibit CYP2D6 activity
Genetic testing laboratories
- Genotyping tests for CYP2D6 variants are commercially available through Applied Biosystems (https://www.appliedbiosystems.com/) and GenPath Diagnostics (https://www.genpathdiagnostics.com/)
