Yes

Antipsychotic Agent, Phenothazine, Piperazine

Management of manifestations of psychotic disorders and schizophrenia; depot formulation may offer improved outcome in individuals with psychosis who are noncompetent with oral antipsychotics

C

Hypersensitivity to fluphenazine or any component (cross reactivity between phenothiazines may occur); severe CNS depression, coma, subcortical brain damage, blood dyscrasias, hepatic disease

May be sedating, use with caution in disorders where CNS depression is a feature. Use with caution in Parkinson's disease. Caution in patients with hemodynamic instability; bone marrow suppression; predisposition to seizures; severe cardiac, renal, or respiratory disease. Esophageal dysmotility and aspiration have been associated with antipsychotic use - use with caution in patients at risk of pneumonia (ie, Alzheimer's disease). Caution in breast cancer or other prolactin-dependent tumors (may elevate prolactin levels). May alter temperature regulation or mask toxicity of other drugs due to antiemetic effects. May alter cardiac conduction; life-threatening arrhythmias have occurred with therapeutic doses of phenothiazines. Hypotension may occur, particularly with I.M. administration. May cause orthostatic hypotension - use with caution in patients at risk of this effect or those who would tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, or other medications which may predispose). Adverse effects of depot injections may be prolonged.

May cause extrapyramidal reactions, including pseudoparkinsonism, acute dystonic reactions, akathisia and tardive dyskinesia (risk of these reactions is high relative to other antipsychotics). May be associated with neuroleptic malignant syndrome (NMS) or pigmentary retinopathy.

Cardiovascular: Hypotension, tachycardia, fluctuations in blood pressure, hypertension, arrhythmias, edema

Central nervous system: Parkinsonian symptoms, akathisia, dystonias, tardive dyskinesia, dizziness, hyper-reflexia, headache, cerebral edema, drowsiness, lethargy, restlessness, excitement, bizarre dreams, EEG changes, depression, seizures, NMS, altered central temperature regulation

Dermatologic: Increased sensitivity to sun, rash, skin pigmentation, itching, erythema, urticaria, seborrhea, eczema, dermatitis

Endocrine & metabolic: Changes in menstrual cycle, breast pain, amenorrhea, galactorrhea, gynecomastia, changes in libido, elevated prolactin, SIADH

Gastrointestinal: Weight gain, loss of appetite, salivation, xerostomia, constipation, paralytic ileus, laryngeal edema

Genitourinary: Ejaculatory disturbances, impotence, polyuria, bladder paralysis, enuresis

Hematologic: Agranulocytosis, leukopenia, thrombocytopenia, nonthrombocytopenic purpura, eosinophilia, pancytopenia

Hepatic: Cholestatic jaundice, hepatotoxicity

Neuromuscular & skeletal: Trembling of fingers, SLE, facial hemispasm

Ocular: Pigmentary retinopathy, cornea and lens changes, blurred vision, glaucoma

Respiratory: Nasal congestion, asthma

Symptoms of overdose include deep sleep, hypotension, hypertension, dystonia, seizures, extrapyramidal symptoms, respiratory failure

Following initiation of essential overdose management, toxic symptom treatment and supportive treatment should be initiated. Hypotension usually responds to I.V. fluids or Trendelenburg positioning. If unresponsive to these measures, the use of a parenteral inotrope may be required. Seizures commonly respond to diazepam (I.V. 5-10 mg bolus in adults every 15 minutes if needed up to a total of 30 mg; I.V. 0.25-0.4 mg/kg/dose up to a total of 10 mg in children) or to phenytoin or phenobarbital. Cardiac arrhythmias often respond to I.V. lidocaine while other antiarrhythmics can be used. Neuroleptics often cause extrapyramidal symptoms (eg, dystonic reactions) requiring management; benztropine mesylate I.V. 1-2 mg (adults) may be effective. These agents are generally effective within 2-5 minutes.

CYP2D6 enzyme substrate; CYP2D6 enzyme inhibitor CYP1A2, 2D6, and 3A3/4 enzyme substrate; CYP2D6 enzyme inhibitor

Benztropine (and other anticholinergics) may inhibit the therapeutic response to fluphenazine and excess anticholinergic effects may occur

Chloroquine may increase fluphenazine concentrations

Cigarette smoking may enhance the hepatic metabolism of fluphenazine. Larger doses may be required compared to a nonsmoker.

Concurrent use of fluphenazine with an antihypertensive may produce additive hypotensive effects

Antihypertensive effects of guanethidine and guanadrel may be inhibited by fluphenazine

Concurrent use with TCA may produce increased toxicity or altered therapeutic response

Fluphenazine may inhibit the antiparkinsonian effect of levodopa; avoid this combination

Fluphenazine plus lithium may rarely produce neurotoxicity

Barbiturates may reduce fluphenazine concentrations

Propranolol may increase fluphenazine concentrations

Sulfadoxine-pyrimethamine may increase fluphenazine concentrations

Fluphenazine and possibly other low potency antipsychotics may reverse the pressor effects of epinephrine

Fluphenazine and CNS depressants (ethanol, narcotics) may produce additive CNS depressant effects

Fluphenazine and trazodone may produce additive hypotensive effects

Fluphenazine used with clonidine has resulted in delirium; monitor

Fluphenazine may inhibit the metabolism of tricyclic antidepressants (desipramine, imipramine, nortriptyline); monitor for altered therapeutic response

Avoid freezing; protect all dosage forms from light; clear or slightly yellow solutions may be used; should be dispensed in amber or opaque vials/bottles. Solutions may be diluted or mixed with fruit juices or other liquids but must be administered immediately after mixing; do not prepare bulk dilutions or store bulk dilutions.

Blocks postsynaptic mesolimbic dopaminergic D₁ and D₂ receptors in the brain; depresses the release of hypothalamic and hypophyseal hormones; believed to depress the reticular activating system thus affecting basal metabolism, body temperature, wakefulness, vasomotor tone, and emesis

Following I.M. or S.C. administration (derivative dependent):

Decanoate (lasts the longest and requires more time for onset):

Onset of action: 24-72 hours

Peak neuroleptic effect: Within 48-96 hours

Hydrochloride salt (acts quickly and persists briefly):

Onset of activity: Within 1 hour

Duration: 6-8 hours

Distribution: Crosses the placenta; appears in breast milk

Metabolism: In the liver

Half-life: Derivative dependent:

Enanthate: 84-96 hours

Hydrochloride: 33 hours

Decanoate: 163-232 hours

Adults:

I.M.: 2.5-10 mg/day in divided doses at 6- to 8-hour intervals (parenteral dose is 1/3 to 1/2 the oral dose for the hydrochloride salts)

I.M. (decanoate): 12.5 mg every 2 weeks

Conversion from hydrochloride to decanoate I.M. 0.5 mL (12.5 mg) decanoate every 3 weeks is approximately equivalent to 10 mg hydrochloride/day

I.M. (enanthate): 12.5-25 mg every 2 weeks

Hemodialysis: Not dialyzable (0% to 5%)

Alcohol: Additive CNS effect, avoid use

Therapeutic: 5-20 ng/mL; correlation of serum concentrations and efficacy is controversial; most often dosed to best response

cholesterol (S), glucose; uric acid (S)

Most pharmacology textbooks state that in presence of phenothiazines, systemic doses of epinephrine paradoxically decrease the blood pressure. This is the so called "epinephrine reversal" phenomenon. This has never been observed when epinephrine is given by infiltration as part of the anesthesia procedure.

Orthostatic hypotension and nasal congestion possible in dental patients. Since the drug is a dopamine antagonist, extrapyramidal symptoms of the TMJ a possibility.

Use exactly as directed (do not increase dose or frequency); may cause physical and/or psychological dependence. Do not discontinue without consulting prescriber. Dilute with water, milk, orange or grapefruit juice; do not dilute with beverages containing caffeine, tannin, or pectinate (eg, coffee, colas, tea, or apple juice). Do not take within 2 hours of any antacid. Avoid excess alcohol or caffeine and other prescription or OTC medications not approved by prescriber. Avoid skin contact with medication; may cause contact dermatitis (wash immediately with warm, soapy water). Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience excess drowsiness, lightheadedness, dizziness, or blurred vision (use caution driving or when engaging in tasks requiring alertness until response to drug is known); dry mouth, upset stomach, nausea, vomiting (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help); postural hypotension (use caution climbing stairs or when changing position from lying or sitting to standing); urinary retention (void before taking medication); ejaculatory dysfunction (reversible); decreased perspiration (avoid strenuous exercise in hot environments); or photosensitivity (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). Report persistent CNS effects (eg, trembling fingers, altered gait or balance, excessive sedation, seizures, unusual movements, anxiety, abnormal thoughts, confusion, personality changes); chest pain, palpitations, rapid heartbeat, severe dizziness; unresolved urinary retention or changes in urinary pattern; altered menstrual pattern, change in libido, swelling or pain in breasts (male or female); vision changes; skin rash or irritation or yellowing of skin; or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Avoid contact of oral solution or injection with skin (contact dermatitis); watch for hypotension when administering I.M. or I.V.; oral liquid to be diluted in the following only: water, saline, 7-UP®, homogenized milk, carbonated orange beverages, pineapple, apricot, prune, orange, V8® juice, tomato, and grapefruit juices

Concentrate, as hydrochloride:

Permitil®: 5 mg/mL with alcohol 1% (118 mL)

Prolixin®: 5 mg/mL with alcohol 14% (120 mL)

Elixir, as hydrochloride (Prolixin®): 2.5 mg/5 mL with alcohol 14% (60 mL, 473 mL)

Injection, as decanoate (Prolixin Decanoate®): 25 mg/mL (1 mL, 5 mL)

Injection, as enanthate (Prolixin Enanthate®): 25 mg/mL (5 mL)

Injection, as hydrochloride (Prolixin®): 2.5 mg/mL (10 mL)

Tablet, as hydrochloride

Permitil®: 2.5 mg, 5 mg, 10 mg

Prolixin®: 1 mg, 2.5 mg, 5 mg, 10 mg

Cheung HK and Yu EC, "Effect of 1050 mg Fluphenazine Decanoate Given Intramuscularly Over Six Days," Br Med J (Clin Res Ed), 1983, 286(6370):1016-7.

Fishbain DA, "Priapism Resulting From Fluphenazine Hydrochloride Treatment Reversed by Diphenhydramine," Ann Emerg Med, 1985, 14(6):600-2.

Oshika T, "Ocular Adverse Effects of Neuropsychiatric Agents. Incidence and Management," Drug Saf, 1995, 12(4):256-63.

Peabody CA, Warner MD, Whiteford HA, et al, "Neuroleptics and the Elderly," J Am Geriatr Soc, 1987, 35(3):233-8.

Risse SC and Barnes R, "Pharmacologic Treatment of Agitation Associated With Dementia," J Am Geriatr Soc, 1986, 34(5):368-76.

Saltz BL, Woerner MG, Kane JM, et al, "Prospective Study of Tardive Dyskinesia Incidence in the Elderly," JAMA, 1991, 266(17):2402-6.

Seifert RD, "Therapeutic Drug Monitoring: Psychotropic Drugs," J Pharm Pract, 1984, 6:403-16.