D2.418 - Tolperisone Hypersensitivity: An Underrecognized Drug Allergy in the Context of Widespread Off-Label Use

Drug hypersensitivity reactions remain a significant clinical challenge. Tolperisone is widely used for acute musculoskeletal pain, frequently in association with non-steroidal anti-inflammatory drugs (NSAIDs), although its approved indication is limited to post-stroke spasticity. Because of this common co-administration, allergic reactions are often attributed to NSAIDs. Moreover, tolperisone use remains limited in several European countries, potentially contributing to underrecognition and underreporting of hypersensitivity reactions.

We present a two-case series of patients evaluated for suspected tolperisone hypersensitivity in an allergology department. Clinical manifestations, timing of symptom onset, associated medication, and diagnostic investigations were analyzed. Drug hypersensitivity was confirmed using fractionated oral provocation tests performed under strict medical supervision, in accordance with international recommendations. Alternative culprit drugs were excluded through targeted testing when clinically indicated.

The first case involved a 47-year-old man who developed acute angioedema of the lips, generalized urticaria, and erythema approximately two hours after oral intake of tolperisone associated with non-steroidal anti-inflammatory drugs (NSAIDs), prescribed for acute low back pain. A fractionated oral provocation test with tolperisone was positive, reproducing cutaneous symptoms, while NSAID hypersensitivity was excluded.

The second case, previously evaluated, involved a 53-year-old woman without a history of atopy or drug allergy, who developed erythema, pruritus, angioedema, and dyspnea shortly after receiving tolperisone in combination with naproxen and esomeprazole. Fractionated OPT confirmed tolperisone hypersensitivity.

Both cases were consistent with immediate-type reactions, ranging from isolated cutaneous involvement to systemic manifestations. Review of local emergency department records suggests tolperisone is among the frequently implicated muscle relaxants in drug-induced allergic reactions in our region.

Tolperisone may represent an underrecognized cause of immediate drug hypersensitivity, particularly when administered concomitantly with NSAIDs, and in context of widespread off-label use. Oral provocation testing remains essential for diagnostic confirmation. Increased awareness is warranted to avoid misattribution of reactions to co-administered drugs.