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

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 adverse effects of psychotropic agents
• drug adverse effects of dopaminergic receptor antagonists
• drug adverse effects of antihypertensive 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 antipsychotics & dopamine receptor agonists
• drug interaction(s) of antipsycotics with benzodiazepines
• drug interaction(s) of beta-adrenergic receptor antagonists with phenothiazines
• drug interaction(s) of NSAIDs & antihypertensives

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
• labs with Loincs
  • fluphenazine in specimen
  • fluphenazine in blood/urine
  • fluphenazine in gastric fluid
  • fluphenazine in serum/plasma
  • fluphenazine in urine

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)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=673536
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3372
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3389
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3388
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=441211