promethazine (Phenergan, Farganesse)

Introduction

Tradename: Phenergan. (promethazine hydrochloride)

Indications

• adjunct to general anesthesia
  • preoperative, postoperative or obstetric sedation
• prevention & control of nausea & vomiting
• adjunct to analgesics for pain management (analgesia)
• antihistamine for the prevention & treatment of motion sickness
• apprehension
• allergies
  • allergic conconjuntivitis
  • urticaria

Contraindications

• angle-closure glaucoma

* 2) children < 2 years of age *

Caution: in children

pregnancy category = c

safety in lactation = -

Dosage

• allergies: 25 mg PO QHS
• nausea/vomiting:
  • 1-2 mg/kg up to 25-50 mg PO/IM/PR every 4-6 hours
• pre-operative sedation: 1-2 mg/kg up to 25-50 mg PO/IM/PR every 4-6 hours
• post-op: 6.25-12.5 mg IV
  • dilute with 10 or 20 mL of normal saline
  • administer through a free-flowing IV
• children: 0.1-0.5 mg/kg IM/IV/PO/PR every 6 hours PRN

Tabs: 12.5, 25, 50 mg.

Syrup: 6.25 & 25 mg/5 mL.

Suppository: 12.5, 25, 50 mg.

Injection: 25 mg/mL (1 mL), 50 mg/mL (1 mL).

Pharmacokinetics

• onset of sedative effect:
  • within 20 minutes following oral, rectal or IM administration
  • within 3-5 minutes after intravenous injection
• metabolized by the liver
• excreted as inactive drug in the urine & feces

elimination via liver

elimination via kidney

Adverse effects

• common (> 10%)
  • slight to moderate drowsiness
  • thickening of bronchial secretions
• less common (1-10%)
  • headache, fatigue, increased appetite, increased weight, nervousness, dizziness, nausea, diarrhea, abdominal pain, dry mouth, pharyngitis, arthralgia
• uncommon (< 1%)
  • angioedema, bronchospasm, depression, edema, epistaxis, hepatitis, myalgia, palpitations, paresthesias, photosensitivity, rash, hypotension, sedation, dizziness, paradoxical excitement, fatigue, insomnia, tremor, blurred vision, urinary retention, sedation (marked), dystonia, faintness with IV administration, irregular respiration
• other
  • anticholinergic effects:
    • dry mouth
    • blurred vision
    • dizziness (rare)
    • sedation
  • extrapyramidal effects with high doses
  • hypotension may occur with rapid IV administration
  • jaundice
  • extravasation with IV use can lead to severe tissue damage including gangrene requiring amputation
  • fatal respiratory depression has occurred *
  • central nervous system depression
    • especially, children < 2 years of age
  • seizures

• drug adverse effects of H1 receptor antagonists

Drug interactions

• other CNS depressants
• MAO inhibitors intensify anticholinnergic effects

• drug interaction(s) of lithium carbonate with phenothiazine
• drug interaction(s) of beta-adrenergic receptor antagonists with phenothiazines

Laboratory

• promethazine in blood
• promethazine in blood/urine
• promethazine in serum/plasma/urine
• promethazine in serum/plasma
• promethazine in urine

Mechanism of action

• agonist at the histamine H1 receptor
• sedative, anti-motion sickness, & local anesthetic effects
• antiemetic effects secondary to anticholinergic effects on the:
  • vestibular apparatus
  • chemoreceptor-trigger zone (CTZ) in the midbrain

More general terms

• phenothiazine
• H1 receptor antagonist (antihistamine)
• anti-emetic

Component of

• codeine/phosphate/promethazine
• codeine/phenylephrine/phosphate/promethazine
• codeine/guaifenesin/promethazine
• meperidine/promethazine
• dextromethorphan/promethazine (Phenergan with dextromethorphan)
• codeine/promethazine (Phenergan with codeine)
• phenylephrine/promethazine (Phenergan with phenylephrine)
• codeine/phenylephrine/promethazine (Phenergan with phenylephrine & codeine)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4927
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=6014
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=657263
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=517306