Oxycodone/naloxone as a therapeutic option in a patient with chronic pain and opioid-induced bowel dysfunction

Cancer-induced pain is a complex issue of utmost importance in everyday clinical practice. Published data show that the majority of patients with advanced or disseminated cancer and between 27% and 60% of ambulatory cancer patients in various stages of the disease may suffer from moderate or severe pain (VAS 5–10) [1, 2].
However, it has been demonstrated that up to 82% of patients with cancer-induced pain may be inadequately treated, with postponed introduction of WHO analgesic ladder third-level drugs in a substantial subset of this population [3, 4]. Unfortunately, ineffectively controlled pain is associated with high risk of unfavourable psychosomatic consequences.
Concern about undesirable effects of potent opioids is undoubtedly one of the main causes of inadequate analgesic treatment as almost 80% of patients experience at least one side effect [5]. Opioids’ side effects are typically mild in intensity and not life-threatening, but they may significantly impair the quality of life.
One of the most important clinical issues in this regard is opioid-induced bowel dysfunction (OIBD). OIBD is mainly manifested by persistent constipation, which is the most frequent undesirable effect of regimens containing opioid analgesics [6, 7]. In a subset of patients the severity of constipation may cause unacceptable decline of the quality of life, despite appropriate laxative treatment or prevention.
Thus, a treatment strategy combining effective analgesia with concomitant maintenance or recovery of proper bowel function should be an attractive option for this patient group. Currently, this goal may be achieved by combined administration of oxycodone with naloxone, with pharmaceutical products containing both these agents in a 2 : 1 ratio, marketed as prolonged-release (PR) tablets.
Oxycodone is a potent opioid analgesic agent belonging to the third rung of the WHO analgesic ladder. It is characterized by high bioavailability after oral administration (up to 87%) and wide distribution in all body compartments. It shows 45% binding to serum proteins, whereas the serum half-life varies between 3 and 5 hours. The drug is metabolized in the liver via the P-450 cytochrome system (CYP3A4, CYP2D6) into active metabolites, which do not play a dominant role in drug pharmacodynamics due to low serum concentrations. Elimination of the drug occurs via urine and faeces, while moderate or severe liver or renal insufficiency increases the exposure...


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