Tapentadol-induced urticarial rash in a patient with acute pancreatitis

Abstract

Tapentadol, a dual-action opioid, is increasingly used for pain management in acute pancreatitis (AP). Although its common side effects are well-documented, cutaneous reactions are rare. We report a 30-year-old gentleman with AP who developed generalized urticaria following oral tapentadol use. The patient had no prior history of atopy or drug allergies. The rash resolved after discontinuation of tapentadol and administration of a short course of corticosteroids and antihistamines. Cutaneous reactions to tapentadol are extremely rare but should be recognized promptly to ensure timely management and prevent unnecessary investigations.

Introduction

Acute pancreatitis (AP) is a highly prevalent gastrointestinal condition that necessitates hospitalization. Abdominal pain is the defining characteristic of AP, prompting immediate analgesia and remaining a paramount concern in the early management of the disease.[1] Several pharmacological options are available for pain management, including paracetamol, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids. Opioids are the most commonly prescribed agents for pain relief in AP. Tapentadol is an opioid analgesic that exerts its analgesic effect through a dual mechanism. It binds to the μ-opioid receptor (MOR) with an affinity at least ten-fold higher than that for delta and kappa opioid receptors. Tapentadol also inhibits noradrenaline reuptake, leading to elevated noradrenaline levels and subsequent activation of α₂-adrenergic receptors, thereby enhancing analgesia.[2] Although the common side effects are well-recognized, cutaneous adverse reactions are rare, with only a few cases reported in the literature, predominantly in drug abusers following intravenous use.[3,4] Here, we report a case of oral tapentadol-induced urticaria, which was successfully managed with a short course of oral corticosteroids and antihistamines.

Case Report

A 30-year-old male with no known comorbidities presented to our outpatient department with a 3-day history of mild-to-moderate upper abdominal pain radiating to the back, which worsened after food intake. There was no history of vomiting, diarrhea, constipation, abdominal distension, jaundice, or fever. He had been treated at an outside hospital with oral rabeprazole, acetaminophen, and tramadol, which provided only partial relief. On examination, he had mild tachycardia (heart rate: 106 beats/min) and epigastric tenderness. On evaluation, his serum amylase and lipase levels were elevated (350 IU and 630 IU, respectively). Contrast-enhanced computed tomography of the abdomen revealed a bulky, heterogeneously enhancing head and uncinate process of the pancreas with peripancreatic inflammation [Figure 1]. His hemogram, liver function tests, and renal function tests were within the normal limits. He was admitted and managed conservatively with intravenous fluids (Ringer’s lactate and dextrose solutions), on-demand intravenous tramadol for analgesia, and kept nil per oral. Oral intake was resumed after 48 h, with a reduction in pain intensity in a Visual Analog Scale (VAS) score from 6/10 to 2/10. After 72 h, he was discharged in a hemodynamically stable condition with prescriptions for on-demand oral tapentadol 100 mg, rabeprazole, and multivitamin supplements. The following day, the patient returned to the outpatient department with complaints of a generalized, itchy rash that developed after taking a tapentadol tablet [Figure 2]. He had been treated at an outside hospital with an injection of pheniramine maleate followed by oral levocetirizine 5 mg, which provided only a partial relief. He had no personal or family history of atopy and no prior history of drug allergies. A dermatology consultation was obtained, and he was diagnosed with drug-induced urticaria. He was successfully treated by discontinuing tapentadol and initiating a short course of oral steroids (prednisolone 20 mg OD for 5 days) along with levocetirizine 5 mg once daily for 1 week. His rash showed gradual improvement over the following 4 days.

Figure 1.

Contrast-enhanced computed tomography of the abdomen showing heterogeneously enhancing bulky head of pancreas (arrow) with peripancreatic fat stranding (arrowhead)

Figure 2.

Multiple well-defined erythematous papulo-plaques were noted over the anteroposterior aspect of the trunk and the ventral aspect of both wrists

Discussion

AP is one of the most common gastrointestinal diseases worldwide, often requiring hospital admission. The global annual incidence of AP is 33.74 per 100,000 person-years.[5] AP is characterized by abdominal pain, vomiting, fever, multiorgan failure, and other symptoms. The diagnosis of AP requires two of the following three features: (i) abdominal pain, (ii) serum lipase or amylase activity at least three times greater than the upper limit of normal, and (iii) imaging evidence of pancreatitis.[6] The most common etiological factors for AP in India were alcohol, followed by gallstones.[7,8] Our index patient had ethanol-related acute necrotizing pancreatitis.

The initial treatment of AP depends on intravenous hydration, analgesics, and adequate nutritional support.[9] Pain management is an important priority in the treatment of AP. There are many pharmacological options, with NSAIDs and opioids being the most frequently prescribed analgesics for pain relief of patients with AP.[1] Compared to NSAIDs, opioids provide more effective pain relief in AP patients, with a significantly lower requirement for rescue analgesics, a longer pain-free interval, greater reduction in VAS scores, and comparable safety.[10,11] In our patient, we managed pain with opioid analgesia (intravenous tramadol during hospital stay and oral tapentadol after discharge).

Tapentadol, an opioid exhibiting dual action as a MOR agonist and a noradrenaline reuptake inhibitor, presents a promising therapeutic option for pain management. The Food and Drug Administration approved its immediate-release formulation in 2008 and extended-release preparation in 2011. Tapentadol’s dual mechanism of action effectively targets both nociceptive and neuropathic pain, resulting in a more favorable efficacy–safety profile compared to conventional opioids. It stands out for its reduced side effects, enhanced tolerability, and minimal drug–drug interactions.[12] The diminished side effect profile in comparison to opioids such as morphine and codeine is attributed to its reduced intrinsic efficacy at the MOR.[13]

However, common side effects of tapentadol include dizziness, drowsiness, headache, nausea, vomiting, constipation, and hypotension. Rare side effects associated with tapentadol use include anaphylaxis, angioedema, ataxia, confusion, hypotension, decreased heart rate, delayed gastric emptying, disorientation, drug dependence, dysarthria, euphoria, hallucinations, hypersensitivity, hypogonadism, cutaneous reactions, and drug-related hepatic disorders; however, these have been reported in <1% of patients.[14]

Human cutaneous mast cells express opioid receptors, and their stimulation can trigger mast cell degranulation, leading to urticarial skin reactions.[15] Due to its diminished affinity for the MOR, cutaneous reactions to tapentadol are uncommon, with only a few instances documented in the literature, predominantly among intravenous drug users.[3,4] In an earlier study, a patient developed a skin allergy during treatment with oral tapentadol (TAPAL-ER 50) for pain control in cancer patients.[16] We report the second documented case of a cutaneous adverse reaction to oral tapentadol in a patient with AP.

Urticaria has been reported to be the second most common cutaneous drug reaction, following morbilliform reactions. It accounts for 5%–22% of all cutaneous drug reactions.[17] The clinical manifestations of drug-induced urticaria are indistinguishable from those of nondrug-induced urticaria. Management entails ceasing the causative drug and employing oral second-generation antihistamines, such as cetirizine, loratadine, fexofenadine, desloratadine, or levocetirizine. In addition, topical lotions such as calamine and menthol containing aqueous cream are useful soothing agents. If urticaria is severe or nonsedating antihistamines alone are ineffective, a 4–5-day course of oral prednisone or prednisolone may be added.[18] In our index patient, acute drug-induced urticaria secondary to oral tapentadol was managed successfully with oral steroids along with the antihistamines.

Conclusion

Pain is a predominant symptom in AP and requires effective management for improved patient outcomes. Tapentadol, as a dual-action opioid, is a promising analgesic option. Clinicians should remain aware of rare adverse reactions of oral tapentadol, including cutaneous manifestations, to ensure timely intervention and avoid unnecessary investigations.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.