Adverse reaction to dextromethorphan


  • We present the case of an adverse reaction to dextromethorphan with positive skin prick test.

Dextromethorphan is a nonrespiratory depressant opiate derivative used alone or in combination with other compounds as symptomatic treatment of cough and its efficacy is similar to that of codeine (1).

A 24-year-old woman presented at our outpatient clinic for a sensation of bolus in the throat with swallowing difficulty, erythema and hives with audible whistling immediately after the first dose of Romilar® (dextromethorphan hydrobromide), which was resolved after treatment with corticosteroids and antihistaminic agents. She had taken Algidol® (paracetamol and codeine) half an hour before the onset of the symptoms. She had previously tolerated Romilar, paracetamol and codeine without any problems.

An allergy study by prick test with Romilar (dextromethorphan) was positive. A skin prick test (SPT) with Romilar was also performed in 10 controls, being positive in three of them.

The SPT with paracetamol and codeine was negative. Oral challenge with paracetamol and codeine was well tolerated. Oral challenge was also performed with another opiod agonist, tramadol, which was well tolerated.

After challenge with dextromethorphan (0.5 ml of the Romilar syrup solution), the patient immediately developed four hive lesions on her back that was resolved after antihistaminic treatment.

Given that the results of the challenge test were doubtful because it was not possible to disguise the taste of the preparation and as the adverse reaction was not severe and the patient requested this drug to control her symptoms, we decided to repeat the challenge test.

In the first place, a placebo having identical taste as Romilar was administered and was well tolerated. Then dextromethorphan was administered and after 0.5 ml of the solution, the patient developed generalized erythema with generalized pruritus and decreased blood pressure. Prompt treatment with adrenaline, steroids and antihistamines relieved the symptoms.

Dextromethorphan is used as an antitussive drug with the same efficacy as codeine but with less subjective or gastrointestinal abnormalities. Unlike other opiates, it has no analgesic power. Its toxicity is low and adverse reactions are rare, the most common being those that affect the central nervous system or psychiatric disorders; rash or urticaria type manifestations and anaphylaxis are totally rare (1).

We have not found any reports of allergic reaction to dextromethorphan with positive skin test. There is one case of anaphylaxis (2) due to dextromethorphan in which no skin test was performed and one case of fixed drug eruption with positive oral challenge but with negative epicutaneous test (3).

Opiate derivatives are nonspecific histamine releasers and induce nonallergic drug hypersensitivity (4).

In our case, it is interesting that the patient has tolerated codeine and tramadol, also nonspecific histamine releasers. Because of this, as well as the positivity of the prick and the rareness of reactions of this type in spite of the wide use of the drug, a mechanism of IgE-mediated drug allergy cannot be ruled out (4).