fluoxetine hydrochloride

Prozac, Prozac Weekly, Prozit (UK), Sarafem

Pharmacologic class: Selective serotonin reuptake inhibitor

Therapeutic class: Antidepressant

Pregnancy risk category B

Action

Selectively inhibits serotonin reuptake in CNS; has little to no effect on norepinephrine and dopamine reuptake

Availability

Capsules: 10 mg, 15 mg, 20 mg, 40 mg

Capsules (delayed-release): 90 mg

Oral solution: 20 mg/5 ml

Tablets: 10 mg, 15 mg, 20 mg

Indications and dosages

➣ Major depressive disorder (MDD)

Adults: 20 mg/day P.O. in morning. After several weeks, may increase by 20 mg/day at weekly intervals. Give dosages above 20 mg/day in two divided doses (morning and noon); don't exceed 80 mg/day. Patients stabilized on 20 mg/day may be switched to 90-mg/week delayed-release capsules (Prozac Weekly) 7 days after last 20-mg dose.

Children ages 8 to 18: Initially, 10 to 20 mg/day P.O. After 1 week at 10 mg daily, dosage should be increased to 20 mg/day. However, because of higher plasma levels in lower-weight children, starting and target dose in this group may be 10 mg/day. Dosage increase to 20 mg/day may be considered after several weeks if insufficient clinical improvement occurs.

➣ Obsessive-compulsive disorder (OCD)

Adults: Initially, 20 mg/day P.O. in morning. After several weeks, may increase dosage. Give doses above 20 mg/day once daily (morning) or in two divided doses b.i.d. (morning and noon). Dosage range of 20 to 60 mg/day is recommended; however, dosages of up to 80 mg/day have been well tolerated. Don't exceed 80 mg/day.

Children ages 7 to 17: Initially, 10 mg/day P.O. in morning in adolescents and higher-weight children; after 2 weeks, may increase dosage to 20 mg/day. Additional dosage increases may be considered after several more weeks if insufficient clinical improvement occurs. Dosage range of 20 to 60 mg/day is recommended. Initially, 10 mg/day P.O. in lower-weight children; may increase dosage after several more weeks if insufficient clinical improvement occurs. Dosage range of 20 to 30 mg/day is recommended. Experience with daily doses greater than 20 mg is very minimal; there is no experience with doses greater than 60 mg.

➣ Acute treatment of depressive episodes associated with bipolar I disorder

Adults: Initially, 20 mg fluoxetine P.O. with 5 mg olanzapine P.O. daily; dosage range of fluoxetine is 20 to 50 mg; olanzapine, 5 to 12.5 mg. Safety of fluoxetine doses above 75 mg and olanzapine doses above 18 mg haven't been established

➣ Bulimia nervosa

Adults: 60 mg/day P.O.; may be titrated upward over several days

➣ Panic disorder

Adults: 10 mg/day P.O. for 1 week; then, if needed, increase to 20 mg/day. Dosage increases of up to 60 mg/day may be considered after several weeks if patient doesn't respond to lower dosage.

➣ Premenstrual dysphoric disorder

Adults: 20 mg/day (Sarafem) P.O., not to exceed 80 mg/day

Dosage adjustment

• Hepatic impairment

• Concurrent disease or multiple concomitant medications

• Pregnant women during third trimester

• Elderly patients

Off-label uses

• Diabetic peripheral neuropathy

• Alcoholism

• Bipolar II disorder

• Borderline personality disorder

• Narcolepsy

• Posttraumatic stress disorder

• Schizophrenia

• Social phobia

Contraindications

• Hypersensitivity to drug

• MAO inhibitor use within past 14 days

• Concurrent use of thioridazine or within 5 weeks of discontinuing fluoxetine

• Concurrent use of pimozide

Precautions

Use cautiously in:

• hepatic or renal impairment, diabetes mellitus, cardiovascular disease, concomitant illness, acute narrow-angle glaucoma

• history of seizures, serotonin syndrome or neuroleptic malignant syndrome, clinical worsening and suicidal thinking and behavior, activation of mania or hypomania

• hyponatremia in association with syndrome of inappropriate antidiuretic hormone secretion

• concurrent use of NSAIDs, aspirin, warfarin, or other drugs that affect coagulation

• concurrent use of tryptophan (use not recommended)

• pregnant patients (third trimester)

• breastfeeding patients (use not recommended)

• children younger than age 7 (in OCD use), younger than age 8 (in MDD use), younger than age 18 for all other uses (safety and efficacy not established).

Administration

See Be aware that drug should be discontinued 5 weeks before MAO inhibitor or thioridazine therapy begins.

• Give before 2 P.M. to prevent nighttime insomnia.

• Be aware that drug should be gradually reduced rather than abruptly stopped whenever possible.

Adverse reactions

CNS: anxiety, drowsiness, headache, insomnia, abnormal dreams, dizziness, fatigue, nervousness, hypomania, mania, weakness, tremor, seizures, suicidal ideation

CV: chest pain, palpitations, prolonged QTc interval

EENT: visual disturbances, stuffy nose, sinusitis, pharyngitis

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, dry mouth, anorexia

GU: urinary frequency, sexual dysfunction, dysmenorrhea

Metabolic: hypouricemia, hypocalcemia, hyponatremia, hyperglycemia, hypoglycemia

Musculoskeletal: joint, back, or muscle pain

Respiratory: cough, upper respiratory tract infection, dyspnea, respiratory distress

Skin: diaphoresis, pruritus, erythema nodosum, flushing, rash

Other: abnormal taste, weight loss, fever, flulike symptoms, hot flashes, serotonin syndrome, neuroleptic malignant syndrome (NMS), allergic reactions, hypersensitivity reactions

Interactions

Drug-drug. Adrenergics: increased sensitivity to adrenergics, increased risk of serotonin syndrome

Alprazolam: decreased metabolism and increased effects of alprazolam

Antihistamines, opioids, other antidepressants, sedative-hypnotics: additive CNS depression

Aspirin, NSAIDs, warfarin, other drugs that affect coagulation: increased risk of GI or other bleeding

Buspirone: potentiation of fluoxetine effects, increased risk of seizures

Carbamazepine, clozapine, digoxin, haloperidol, lithium, phenytoin, warfarin: increased blood levels of these drugs, greater risk of adverse reactions

CYP450-2D6 inducers: increased effects of these drugs

Cyproheptadine: decrease in or reversal of fluoxetine effects

Digoxin, warfarin, other highly protein-bound drugs: increased risk of adverse reactions to either drug

Efavirenz, ritonavir, saquinavir, other CYP450 inhibitors: serotonergics, triptans: increased risk of serotonin syndrome

MAO inhibitors: confusion, agitation, seizures, hypertension, and hyperpyrexia (serotonin syndrome)

Pimozide: increased risk of drug interaction or QTc-interval prolongation

Thioridazine: increased risk of QTc-interval prolongation or potential for elevated thioridazine plasma level

Other antidepressants, phenothiazines, risperidone, tryptophan: increased risk of adverse reactions

Ritonavir: increased ritonavir blood level

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, blood urea nitrogen, creatine kinase, electrolytes, glucose: increased levels

Sodium: decreased level

Drug-herbs. St. John's wort: increased risk of serotonin syndrome

Drug-behaviors. Alcohol use: additive CNS depression

Patient monitoring

See Monitor patient for signs and symptoms of depression. Assess for suicidal ideation.

See Evaluate neurologic status, watching especially for seizures.

See Monitor cardiovascular status, particularly for prolonged QTc interval.

• Assess weight regularly. Watch for signs of eating disorders.

See Monitor patient for signs and symptoms of allergic reactions, serotonin syndrome, or NMS-like reactions. Discontinue drug immediately and initiate supportive treatment if these reactions occur.

Patient teaching

• Encourage patient to establish effective bedtime routine to minimize sleep disorders.

• Tell patient drug may take 4 weeks or longer to be fully effective.

See Instruct patient to contact prescriber if he develops worsening depression or has suicidal thoughts.

See Instruct patient to immediately stop drug and report signs and symptoms of allergic reactions (rash), serotonin syndrome, or neuroleptic malignant syndrome-like reactions.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• Tell female patient to inform prescriber if she is pregnant or breastfeeding.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.