perphenazine (Trilafon)

Introduction

Tradename: Trilafon.

Indications

• symptomatic management of psychotic disorders
• chemotherapy-induced nausea & vomiting

Contraindications

• narrow-angle glaucoma
• bone marrow suppression
• severe liver disease
• severe cardiac disease

Caution:

• seizure disorder
• safety in children < 12 years of age has not been established

pregnancy category = c

safety in lactation = ?

Dosage

• 5 mg IM/IV every 6 hours
  • dilute IV injection to 0.5 mg/mL with normal saline & infuse at 1 mg/min
• 4-8 mg PO TID with water or juice
• elderly: 2-12 mg daily

Tabs: 2, 4, 8, 16 mg.

Liquid: 16 mg/5 mL.

Injection: 5 mg/mL (1 mL)

Pharmacokinetics

• see chlorpromazine
• metabolized in the liver by cyt P450 2D6

elimination via liver

elimination via kidney

Adverse effects

• common (> 10%)
  • pseudoparkinsonism, akathisia, dystonia, hypotension, pigmentary retinopathy, tardive dyskinesia (persistent), constipation, decreased sweating, dizziness, orthostatic hypotension, nasal congestion
• less common (1-10%)
  • difficulty urinating, photosensitivity, rash, changes in menstrual cycle, ejaculatory dysfunction, changes in libido, breast pain, weight gain, nausea/vomiting, epigastric pain, trembling of fingers
• uncommon (< 1%)
  • agranulocytosis, cholestatic jaundice, neuroleptic malignant syndrome, priapism, blue-gray discoloration of the skin, impairment of temperature regulation, galactorrhea, leukopenia, hepatotoxicity, changes in the cornea & lens
• other
  • low sedation
  • low anticholinergic effects
  • low orthostatic hypotension effects
  • high incidence of extrapyramidal symptoms
    • pseudoparkinsonism
    • dystonias
    • akathisia
  • neuroleptic malignant syndrome (rare)
  • tardive dyskinesia (persistent)
  • QT prolongation
  • direct myocardial depression
  • lowering of seizure threshold
• black box warning
  • increased risk of hyperglycemia
  • increased risk of cerebrovascular events
  • increased risk of mortality in patients with dementia

• drug adverse effects of antipsychotic agents
• drug adverse effects of psychotropic agents

Drug interactions

• see chlorpromazine
• avoid terfenadine, astemizole & other agents which prolong the QT interval
• perphenazine inhibits cyt P450 2D6
  • inhibits its own metabolism
  • may increase levels & effects of drugs metabolized by cyt P450 2D6
• any drug that inhibits cyt P450 2D6 may increase levels of perphenazine

• 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

Mechanism of action

high-potency antipsychotic agent

More general terms

• phenothiazine
• antipsychotic agent

Additional terms

• cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)

Component of

• amitriptyline/perphenazine (Etrafon, Triavil)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4748
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=199967
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=656661
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=62871
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=62873
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=76557
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=74835