Fluphenazine

From Anvita Health Wiki

Contents 1 Introduction 2 Indications 3 Contraindications 4 Dosage 5 Pharmacokinetics 6 Adverse-effects 7 Drug-interactions 8 Laboratory 9 Mechanism-of-action 10 More General Terms 11 Additional Terms 12 Internet Database 13 References

Introduction

• Tradenames: Permitil, Prolixin. ( hydrochlorides) (fluphenazine hydrochloride, enanthate, decanoate)

Indications

• symptomatic management of psychiatric disorders
• generally used in combination with anticholinergic agent, i.e. Cogentin

Contraindications

• narrow-angle glaucoma
• bone marrow depression
• severe liver or cardiac disease
• cross-sensitivity to other phenothiazines may exist
  

• pregnancy category = ?
• safety in lactation = ?

Dosage

• 1.25 mg IM every 6-8 hours (observe for hypotension)
• 1-2 mg PO every 6-8 hours

• Tabs: 1, 2.5, 5, 10 mg.
• Elixir: 2.5 mg/5 mL.
• Prolixin decanoate 12.5-25 mg IM every 2-4 weeks.
• Injection: ( decanoate) 25 mg/mL (5 mL)
• Avoid contact of oral solution or injection with skin.
• Risk of contact dermatitis

Pharmacokinetics

• rapidly absorbed from the GI tract & from parenteral sites
• onset of action for decanoate is within 24-72 hours
• duration of action is 1-6 weeks
  

• elimination via liver
• elimination via kidney
• 1/2life = 13-58 hours
• protein binding = >99 %

Adverse-effects

• common (> 10%)

• extrapyramidal symptoms (very common)

• pseudoparkinsonism
• akathisia
• dystonias
• tardive dyskinesia

• 10-20% of patients on long term therapy
• generally irreversible

• hypotension & orthostatic hypotension
• pigmentary retinopathy
• constipation
• decreased sweating
• dizziness
• nasal congestion

• less common (1-10%)

• difficulty urinating, photosensitivity, rash, changes in menstrual cycle, impotence, breast tenderness, weight gain, nausea/vomiting, stomach pain, trembling of fingers

• uncommon (< 1%)

• agranulocytosis, leukopenia, priapism, neuroleptic malignant syndrome (rare), blue-gray discoloration of skin, galactorrhea impairment of temperature regulation, hepatotoxicity, cholestatic jaundice, lowering of seizure threshold, cornea & lens changes, pigmentary retinopathy

• other

• low sedation, low anticholinergic, low orthostatic hypotension effects
• QT prolongation
• direct myocardial depression
  
• drug adverse effects of antipsychotic agents

Drug-interactions

• see chlorpromazine
• risk of QT prolongation & torsades de pointes with astemizole, terfenadine & cisapride
• fluphenazine may inhibit metabolism of some beta-blockers
• tricyclic antidepressants may inhibit metabolism of fluphenazine
  
• drug interaction(s) of lithium carbonate with phenothiazine
• drug interaction(s) of antipsycotics with benzodiazepines
• drug interaction(s) of beta-adrenergic receptor antagonists with phenothiazines

Laboratory

• specimen:

• plasma ( heparin)
• stable for at least 3 weeks at -20 degrees C

• methods: GC, GC-MS, HPLC, RIA
• interferences:

• RIA: prochlorperazine, perphenazine, trifluoperazine, fluphenazine metabolites
• fluphenazine may be displaced from protein- binding sites by plasticizers in collecting devices

Mechanism-of-action

• high potency dopamine D2 receptor antagonist.

More General Terms

• phenothiazine
• antipsychotic agent
• dopaminergic receptor antagonist

Additional Terms

• benztropine <mesylate> (Cogentin)
• chlorpromazine (Thorazine, Ormazine, Propaphenin, Sonazine, Chloractil)

Internet Database

PubChem: 673536
PubChem: 3372
PubChem: 3389
PubChem: 3388
PubChem: 441211

References

1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 1147
3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
5. Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995

fluphenazine (Prolixin, Anatensol, Triflumethazine, Calmansial, Modecate)