fluoxetine PROZAC
Class: SSRIFDA Indications: MDD, OCD, Bulimia Nervosa, Panic Disorder, Treatment Resistant Depression, Depressive Episodes Assoc W/ Bipolar I Disorder, Myoclonus, PMDD
Off-Label Use: Premature Ejaculation, Fibromyalgia, Neurocardiogenic Syncope, Borderline Personality Disorder, PTSD, Raynaud Phenomenon, Social Anxiety
Prescribing
Forms: 10, 20, 40mg capsule; 10, 20, 60mg tablet; 20mg/5mL po solnDose Range: 10-80 mg/day
Starting: 20 mg/day qam; may ↑ after several weeks by 20 mg/day increments; max 80 mg/day
Stopping: Because of long t½ taper is rarely needed as fluoxetine "auto-tapers"
Precautions
Contraindications: Concomitant use of MAOIsSerious Side Effects: Serotonin syndrome; ↑ risk of SI in children and young adults; may impair platelet aggregation; SIADH
Conditional Risk of TdP
Side Effects: nausea, diarrhea, anorexia, insomnia, xerostomia, sedation/somnolence, decreased libido, tremor, hyperhidrosis
Pharmacodynamics
1° MOA: Selective serotonin reuptake inhibitorTarget: SERT, 5-HT2C (antagonist)
Pharmacokinetics
t½: 60 (24-144)° TMAX: 6-8°Substrate of: 2D6; 3A4
Inhibits: 2D6, 3A4 (potent); 2C9/2C19 (moderate); Induces: ∅
Active Metabolites: Norfluoxetine (t½ 200-330°)
DDIs
- - DO NOT CO-PRESCRIBE WITH MAOIs (need a 5-week washout period)
- - 2D6 inhibitors can ↑ its serum levels
- - fluoxetine's 2D6/3A4/2C9/2C19 inhibition can ↑ levels of 2D6/3A4/2C9/2C19 substrates
Misc
- - only antidepressant specifically approved for use in children (depression and OCD)
- - only SSRI with an FDA indication for eating disorders
- - long t½ of drug & its metabolites means dose Δ's won't be reflected in plasma levels for weeks
- - relatively safe in CV patients
- - 5HT2C antagonism has a net disinhibiting effect on NE & DA, which may account for its "activating" effects
- - more prone to result in weight loss compared to other SSRIs
- - nonlinear pharmacokinetics; inhibits its own metabolism
- - ∅ QTc prolongation
Special Populations
Category C—Is not a major teratogen. One animal study has shown that fluoxetine can produce changes, perhaps permanently, in the fetal brain; may adversely affect embryonic development. Two large case-control studies did find increased risks for some birth defects, but the absolute risk appears to be small. SSRIs in general have been associated with several developmental toxicities, including spontaneous abortions, low birth weight, prematurity, neonatal serotonin syndrome, neonatal behavioral syndrome (withdrawal), possibly sustained abnormal neurobehavior beyond the neonatal period, respiratory distress, and persistent pulmonary hypertension of the newborn (PPHN).
Highest RID (1.6-14.6%) among the SSRIs; ∅AE's have been reported for majority of fluoxetine-exposed infants; conflicting reports about effects on growth curves; the American Academy of Pediatrics classified the effects of fluoxetine on the nursing infant to be unknown but may be of concern
Start low with dosage ↑ of 10 & 20 mg q several weeks; can cause agitation, sleep disturbances, & ↑CNS stimulation in elderly.
Use with caution in patients with severe renal impairment
Administer a lower dose or less frequent dosing interval due to long t½