Buprenorphine transdermal patch induced intractable vomiting in a low backache patient. Are unmonitored patches safe?

INTRODUCTION

Buprenorphine transdermal patches (TPs) offer a convenient and sustained method of drug delivery and thus have achieved popularity for the management of both acute and chronic pain of varied aetiologies.^1,2 As a preferable alternative to oral and parenteral formulations, it avoids painful skin punctures and multiple dosing. Further, due to slow release of the drug and evading sudden peaks in the plasma levels, buprenorphine TPs reduce the occurrence of breakthrough pain and thus the requirement of rescue analgesics.^1,2 However, adverse effects, including nausea and vomiting, though rare, require careful consideration. We describe buprenorphine TP-induced intractable vomiting in a patient who had presented to us with acute exacerbation of chronic low back pain (LBP).

THE CASE

A 45-year-old female with a body mass index (BMI) of 25.9 kg/m² visited our pain clinic with an acute exacerbation of chronic LBP associated with radiculopathy of bilateral lower limbs. She was known to have L3-L4 and L4-L5 prolapsed intervertebral disc (PIVD) for the past 6 months and was on conservative manage-ment. There was no motor involvement. Bladder and bowel functions were intact. She was hypothyroid, controlled on 50 μg levothyroxine once daily. We prescribed a combination of oral pregabalin 75 mg, methylcobalamin 1500 μg, and nortriptyline 10 mg once daily for 15 days, oral tolperisone 150 mg sustained release for 10 days, and oral aceclofenac (100 mg) and paracetamol (325 mg) twice daily for 5 days. In addition, due to acute moderate-to-severe pain, we applied buprenorphine TP containing 10 mg with a drug delivery rate of 10 μg/hour. She was instructed to follow up in our clinic after 15 days. However, the next day, she visited our clinic with complaints of 6–7 episodes of vomiting with persistent nausea over the past 24 hours. This was associated with constipation. However, she did not report any abdominal pain. On examination, she was dehydrated, though afebrile with intact sensorium. We admitted her on a daycare basis and initiated fluid resuscitation. Arterial blood gas analysis revealed compensated metabolic alkalosis. Ultrasonography of the abdomen did not reveal any significant findings. Complete blood count, kidney and liver function tests, and serum electrolytes were also within normal limits. Recognising the probable association between buprenorphine TP and vomiting, the patch was removed. Antiemetic medications, including ondansetron 4 mg IV and dexamethasone 8 mg IV was administered to manage acute symptoms. Over a period of 6 hours, she had no further episodes of vomiting, and nausea subsided. After rehydration with 1 litre of crystalloid, she was discharged with the advice to continue oral ondansetron 4 mg thrice daily for another 24 hours and then as the need arose. On telephonic consul-tation for the next two days, she had no more episodes of vomiting.

DISCUSSION

Buprenorphine is a semisynthetic mixed agonist-antagonist opioid analgesic; it exerts agonistic effects at the μ (mu) opioid receptor and antagonistic effects at the κ (kappa) and δ (delta) opioid receptors in the central nervous system.¹ Buprenorphine achieves effective analgesia at relatively low receptor occupancy (5–10%) and thus relatively low plasma concentrations of buprenorphine are sufficient to provide effective pain relief.² This drug has a distinct and complex pharmacological profile, which leads to improved therapeutic advantages and a good safety profile. The creation of a novel transdermal drug delivery method for buprenorphine has rekindled interest in this hitherto under-utilised medication. Steady-state plasma concentrations are reached within 48 hours of the first application of buprenorphine TPs.³ Buprenorphine TPs delivering 5, 10, or 20 μg/hour for 7 days are widely marketed in India.

A retrospective cohort study of the 7-day buprenorphine TPs in general practice showed improved patient compliance with treatment for 6 and 12 months, when compared with codeine, dihydrocodeine, and tramadol; however, there was an increased incidence of nausea, vomiting, dizziness, and constipation associated with the use of the patch.⁴ The transdermal route, while reducing peaks and troughs, can still elicit adverse effects. Nausea and/or vomiting are one of the most common side-effects reported by patients after application of buprenorphine TP.⁵ However, our patient had intractable vomiting (without spontaneous resolution) and required removal of the patch and administration of antiemetics. Although the precise mechanisms of opioid-induced nausea and vomiting (OINV) are not entirely certain, postulated mechanisms include (i) enhanced vestibular sensitivity, (ii) direct effects on the chemoreceptor trigger zone, and (iii) delayed gastric emptying.^6,7 In addition, inter-individual variability, comorbid conditions, genetic preponderance, dose of the drug and concomitant medication might increase the susceptibility to this side-effect. Females show a higher predilection to OINV than males.⁸ Further, our patient was hypothyroid, which could have increased the susceptibility to OINV by altering drug metabolism. An increased dose (10 μg/hour instead of 5 μg/hour) could also be a contributing factor. Aceclofenac is known to cause occasional nausea and/or vomiting secondary to dyspepsia;⁹ however, our patient was not a novice candidate to aceclofenac. She had received oral aceclofenac in the past without such a side effect.

Monitoring of patients on opioids, even with TPs, is warranted. Early recognition of the side effects is the key. Initiation of buprenorphine TP with the lowest dose (5 μg/hour) could be a reasonable strategy followed by incremental dosing if well tolerated. Removal of TP with rescue antiemetics is the currently known management.