<p>Safe Use of Opioids in Chronic Kidney Disease and Hemodialysis Patients: Tips and Tricks for Non-Pain Specialists</p>

Abstract

In patients suffering from moderate-to-severe chronic kidney disease (CKD) or end-stage renal disease (ESRD), subjected to hemodialysis (HD), pain is very common, but often underestimated. Opioids are still the mainstay of severe chronic pain management; however, their prescription in CKD and HD patients is still significantly low and pain is often under-treated. Altered pharmacokinetics and the lack of clinical trials on the use of opioids in patients with renal impairment increase physicians’ concerns in this specific population. This narrative review focused on the correct and safe use of opioids in patients with CKD and HD. Morphine and codeine are not recommended, because the accumulation of their metabolites may cause neurotoxic symptoms. Oxycodone and hydromorphone can be safely used, but adequate dosage adjustments are required in CKD. In dialyzed patients, these opioids should be considered as second-line agents and patients should be carefully monitored. According to different studies, buprenorphine and fentanyl could be considered first-line opioids in the management of pain in CKD; however, fentanyl is not appropriate in patients undergoing HD. Tapentadol does not need dosage adjustment in mild-to-moderate renal impairment conditions; however, no data are available on its use in ESRD. Opioid-related side effects may be exacerbated by common comorbidities in CKD patients. Opioid-induced constipation can be managed with peripherally-acting-μ-opioid-receptor-antagonists (PAMORA). Unlike the other PAMORA, naldemedine does not require any dose adjustment in CKD and HD patients. Accurate pain diagnosis, opioid titration and tailoring are mandatory to minimize the risks and to improve the outcome of the analgesic therapy.

Methadone substitution therapy: Diagnostic challenges in the general practice

“…When GFR <60 ml/min/1,73 m 2 , it is necessary to lower opioid dose 17 . Methadone is excreted with feces which makes it quite safe in patients with CKD, considering their plasma concentrations are similar to controls 18 . However, added damage caused by opiate abuse relapses should be considered, as well as concomitant use of alcohol and anxyolitics.…”

“…However, added damage caused by opiate abuse relapses should be considered, as well as concomitant use of alcohol and anxyolitics. The final goal doesn`t bezbednim za upotrebu u bolesnika sa hroničnom bubrežnom bolešću, budući da su koncentracije u plazmi kod ovih pacijenata slične onima kod kontrolnih ispitanika 18 . Međutim, treba imati u vidu dodatnu štetnost po zdravlje koju izazivaju relapsi u zloupotrebi opijata kao i kontomitantna upotreba alkohola i anksiolitika.…”

Current and Future Therapeutic Options in Pain Management: Multi-mechanistic Opioids Involving Both MOR and NOP Receptor Activation

“…Buprenorphine is mainly metabolized by the liver, therefore it is safe in patients with renal impairment [ 81 ], even when the glomerular filtration rate is lower than 30 mL/min and in patients with end-stage renal disease, undergoing hemodialysis, where pain is very common and often under-treated [ 82 ]. Buprenorphine is particularly suitable for elderly patients [ 83 ], as its metabolism remains quite stable with age and the possibility of drug–drug interactions with other drugs prescribed for comorbidities is lower than classical opioids [ 84 ].…”

Pain Management in Childhood Leukemia: Diagnosis and Available Analgesic Treatments

“…Due to its lower µ-opioid load (MOR affinity is 50 times lower than that of morphine), tapentadol has a favorable tolerability profile, in terms of gastrointestinal adverse events [28,29] and endocrine effects such as no significant changes in testosterone concentration [30]. Furthermore, this molecule is associated with a low risk of drug-drug interactions at the CYP450 level, and may therefore be used in poly-treated patients [31]. Tapentadol is the first and only drug in Europe to have been developed by a multinational pediatric drug development program for children aged 2 to <8 years of age [32].…”