Promethazine

Products

In many countries, drugs containing promethazine are currently no longer on the market. The last product to be withdrawn from the market was Rhinathiol promethazine with the expectorant carbocisteine on January 31, 2009. However, medicines are still available in many countries. The original drug is Phenergan. Promethazine was developed in the 1940s at Rhône-Poulenc, which is now part of Sanofi.

Structure and properties

Promethazine (C17H20N2S, Mr = 284.4 g/mol) belongs to the phenothiazines and exists as a racemate. It is present in drugs as promethazine hydrochloride, a white, crystalline, practically odorless, and hygroscopic powder that is very soluble in water.

Effects

Promethazine (ATC D04AA10, ATC R06AD02) has antihistamine (antiallergic), anticholinergic, antiserotonergic, sedative, hypnotic, weak antipsychotic, barely antidopaminergic, and antiemetic and antivertiginous properties. Effects occur about 20 minutes after ingestion and last 6 to 12 hours.

Indications for use

The following are the main indications for use. Promethazine is not approved for these indications in all countries.

  • Agitation and agitation states in the context of underlying psychiatric disorders.
  • Nausea and vomiting, motion sickness
  • Sleep disorders
  • Cough
  • Allergies, hives
  • Insect bites, skin irritation, sunburn (topical).

Abuse

Promethazine is abused as an intoxicant due to its sedative (sedative) properties. Along with codeine, it is the main ingredient in Purple Drank. Several deaths have been reported in this context. Abuse is therefore strongly discouraged.

Dosage

According to the SmPC. Promethazine is administered perorally (drops, tablets), parenterally (solution for injection), rectally (suppositories), and topically (cream).

Contraindications

  • Hypersensitivity
  • Acute intoxication with central depressant drugs or alcohol
  • Severe blood cell or bone marrow injury
  • Circulatory shock or coma
  • History of known malignant neuroleptic syndrome following the administration of promethazine
  • Children and adolescents

For complete precautions, see the drug label.

Interactions

Promethazine is a substrate of CYP2D6 and has a high potential for interaction. Drug-drug interactions have been described with central depressant drugs, anticholinergics, antidepressants, MAO inhibitors, epinephrine, antihypertensives, antiepileptic drugs, and drugs that prolong the QT interval, among others.

Adverse effects

Possible adverse effects include (selection):

  • Sleep disturbance, confusion, agitation, paradoxical CNS stimulation.
  • Sedation, fatigue
  • Extrapyramidal disorders
  • Increase in intraocular pressure, accommodation disorders.
  • Feeling of a stuffy nose
  • Dry mouth, thirst, cholestasis, constipation.
  • Sweating
  • Micturition disorders
  • Skin reactions

Promethazine may prolong the QT interval and very rarely cause cardiac arrhythmias. An overdose can be life-threatening.