ADVERSE REACTIONS
The safety of oxycodone hydrochloride extended-release tablets was evaluated in double-blind clinical trials involving 713 patients with moderate to severe pain of various etiologies. In open-label studies of cancer pain, 187 patients received oxycodone hydrochloride extended-release tablets in total daily doses ranging from 20 mg to 640 mg per day. The average total daily dose was approximately 105 mg per day.
Serious adverse reactions which may be associated with oxycodone hydrochloride extended-release tablet therapy in clinical use are those observed with other opioid analgesics, including respiratory depression, apnea, respiratory arrest, and (to an even lesser degree) circulatory depression, hypotension, or shock (see OVERDOSAGE).
The non-serious adverse events seen on initiation of therapy with oxycodone hydrochloride extended-release tablets are typical opioid side effects. These events are dose-dependent, and their frequency depends upon the dose, the clinical setting, the patient's level of opioid tolerance, and host factors specific to the individual. They should be expected and managed as a part of opioid analgesia. The most frequent (>5%) include: constipation, nausea, somnolence, dizziness, vomiting, pruritus, headache, dry mouth, sweating, and asthenia.
In many cases the frequency of these events during initiation of therapy may be minimized by careful individualization of starting dosage, slow titration, and the avoidance of large swings in the plasma concentrations of the opioid. Many of these adverse events will cease or decrease in intensity as oxycodone hydrochloride extended-release tablets therapy is continued and some degree of tolerance is developed.
Clinical trials comparing oxycodone hydrochloride extended-release tablets with immediate-release oxycodone and placebo, revealed a similar adverse event profile between oxycodone hydrochloride extended-release tablets and immediate-release oxycodone. The most common adverse events (>5%) reported by patients at least once during therapy were:
Table 3 | Oxycodone Hydrochloride Extended-Release Tablets (n=227) | Oxycodone Hydrochloride Immediate-Release Tablets (n=225) | Placebo (n=45) |
| (%) | (%) | (%) |
| Constipation | 23 | 26 | 7 |
| Nausea | 23 | 27 | 11 |
| Somnolence | 23 | 24 | 4 |
| Dizziness | 13 | 16 | 9 |
| Pruritus | 13 | 12 | 2 |
| Vomiting | 12 | 14 | 7 |
| Headache | 7 | 8 | 7 |
| Dry Mouth | 6 | 7 | 2 |
| Asthenia | 6 | 7 | -- |
| Sweating | 5 | 6 | 2 |
The following adverse experiences were reported in oxycodone hydrochloride extended-release tablets treated patients with an incidence between 1% and 5%. In descending order of frequency they were anorexia, nervousness, insomnia, fever, confusion, diarrhea, abdominal pain, dyspepsia, rash, anxiety, euphoria, dyspnea, postural hypotension, chills, twitching, gastritis, abnormal dreams, thought abnormalities, and hiccups.
The following adverse reactions occurred in less than 1% of patients involved in clinical trials or were reported in post marketing experience:
General: accidental injury, chest pain, facial edema, malaise, neck pain, pain, and symptoms associated with either an anaphylactic or anaphylactoid reaction
Cardiovascular: migraine, syncope, vasodilation, ST depression
Digestive: dysphagia, eructation, flatulence, gastrointestinal disorder, increased appetite, nausea and vomiting, stomatitis, ileus
Hemic and Lymphatic: lymphadenopathy
Metabolic and Nutritional: dehydration, edema, hyponatremia, peripheral edema, syndrome of inappropriate antidiuretic hormone secretion, thirst
Nervous: abnormal gait, agitation, amnesia, depersonalization, depression, emotional lability, hallucination, hyperkinesia, hypesthesia, hypotonia, malaise, paresthesia, seizures, speech disorder, stupor, tinnitus, tremor, vertigo, withdrawal syndrome with or without seizures
Respiratory: cough increased, pharyngitis, voice alteration
Skin: dry skin, exfoliative dermatitis, urticaria
Special Senses: abnormal vision, taste perversion
Urogenital: amenorrhea, decreased libido, dysuria, hematuria, impotence, polyuria, urinary retention, urination impaired
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