Oxycodone Hydchloride

Oxycodone hydrochloride tablets are an immediate-release oral formulation of oxycodone hydrochloride indicated for the management of moderate to severe pain where the use of an opioid analgesic is appropriate.

Oxycodone hydrochloride tablets are contraindicated in patients with known hypersensitivity to oxycodone, or in any situation where opioids are contraindicated. This includes patients with significant respiratory depression (in unmonitored settings or the absence of resuscitative equipment) and patients with acute or severe bronchial asthma or hypercarbia. Oxycodone hydrochloride tablets are contraindicated in any patient who has or is suspected of having paralytic ileus.

Respiratory Depression Respiratory depression is the chief hazard from all opioid agonist preparations. Respiratory depression occurs most frequently in elderly or debilitated patients, usually following large initial doses in non-tolerant patients, or when opioids are given in conjunction with other agents that depress respiration. Oxycodone hydrochloride tablets should be used with extreme caution in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and in patients having substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression. In such patients, even usual therapeutic doses of oxycodone hydrochloride tablets may decrease respiratory drive to the point of apnea. In these patients alternative non-opioid analgesics should be considered, and opioids should be employed only under careful medical supervision at the lowest effective dose. Hypotensive Effect Oxycodone hydrochloride tablets, like all opioid analgesics, may cause severe hypotension in an individual whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs such as phenothiazines or other agents which compromise vasomotor tone. Oxycodone hydrochloride tablets may produce orthostatic hypotension in ambulatory patients. Oxycodone hydrochloride tablets, like all opioid analgesics, should be administered with caution to patients in circulatory shock, since vasodilatation produced by the drug may further reduce cardiac output and blood pressure. Head Injury and Increased Intracranial Pressure The respiratory depressant effects of narcotics and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure. Furthermore, narcotics produce adverse reactions which may obscure the clinical course of patients with head injuries.

General Oxycodone hydrochloride tablets are intended for use in patients who require oral pain therapy with an opioid agonist. As with any opioid analgesic, it is critical to adjust the dosing regimen individually for each patient (see DOSAGE AND ADMINISTRATION ). Selection of patients for treatment with oxycodone hydrochloride tablets should be governed by the same principles that apply to the use of other potent opioid analgesics. Opioid analgesics given on a fixed-dosage schedule have a narrow therapeutic index in certain patient populations, especially when combined with other drugs, and should be reserved for cases where the benefits of opioid analgesia outweigh the known risks of respiratory depression, altered mental state, and postural hypotension. Physicians should individualize treatment in every case, using nonopioid analgesics, prn opioids and/or combination products, and chronic opioid therapy with drugs such as oxycodone hydrochloride tablets in a progressive plan of pain management such as outlined by the World Health Organization, the Agency for Health Care Policy and Research, and the American Pain Society. Use of oxycodone hydrochloride tablets is associated with increased potential risks and should be used only with caution in the following conditions: acute alcoholism; adrenocortical insufficiency (e.g., Addison's disease); convulsive disorders; CNS depression or coma; delirium tremens; debilitated patients; kyphoscoliosis associated with respiratory depression; myxedema or hypothyroidism; prostatic hypertrophy or urethral stricture; severe impairment of hepatic, pulmonary or renal function; and toxic psychosis. The administration of oxycodone hydrochloride tablets, like all opioid analgesics, may obscure the diagnosis or clinical course in patients with acute abdominal conditions. Oxycodone may aggravate convulsions in patients with convulsive disorders, and all opioids may induce or aggravate seizures in some clinical settings. Tolerance and Physical Dependence Physical dependence and tolerance are not unusual during chronic opioid therapy. Significant tolerance should not occur in most patients treated with the lowest doses of oxycodone. It should be expected, however, that a fraction of patients will develop some degree of tolerance and require progressively higher dosages of oxycodone hydrochloride tablets to maintain pain control during chronic treatment. The dosage should be selected according to the patient's individual analgesic response and ability to tolerate side effects. Tolerance to the analgesic effects of opioids is usually paralleled by tolerance to side effects except for constipation. Physical dependence results in withdrawal symptoms in patients who abruptly discontinue the drug or may be precipitated through the administration of drugs with opioid antagonist activity. If oxycodone hydrochloride tablets are abruptly discontinued in a physically dependent patient, an abstinence syndrome may occur (see DRUG ABUSE AND DEPENDENCE ). If signs and symptoms of withdrawal occur, patients should be treated by reinstitution of opioid therapy followed by gradual tapered dose reduction of oxycodone hydrochloride tablets combined with symptomatic support (see DOSAGE AND ADMINISTRATION : Cessation of Therapy ). Use in Pancreatic/Biliary Tract Disease Oxycodone hydrochloride tablets may cause spasm of the sphincter of Oddi and should be used with caution in patients with biliary tract disease, including acute pancreatitis. Opioids like oxycodone hydrochloride tablets may cause increases in the serum amylase level. Information for Patients/Caregivers If clinically advisable, patients (or their caregivers) receiving oxycodone hydrochloride tablets should be given the following information by the physician, nurse, pharmacist or caregiver: Patients should be advised to report episodes of breakthrough pain and adverse experiences occurring during therapy. Individualization of dosage is essential to make optimal use of this medication. Patients should be advised not to adjust the dose of oxycodone hydrochloride tablets without consulting the prescribing professional. Patients should be advised that oxycodone hydrochloride tablets may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g. driving, operating heavy machinery). Patients should not combine oxycodone hydrochloride tablets with alcohol or other central nervous system depressants (sleep aids, tranquilizers) except by the orders of the prescribing physician, because additive effects may occur. Women of childbearing potential who become, or are planning to become, pregnant should be advised to consult their physician regarding the effects of analgesics and other drug use during pregnancy on themselves and their unborn child. Patients should be advised that oxycodone hydrochloride tablets are a potential drug of abuse. They should protect them from theft, and they should never be given to anyone other than the individual for whom they were prescribed. Patients should be advised that if they have been receiving treatment with oxycodone hydrochloride tablets for more than a few weeks and cessation of therapy is indicated, it may be appropriate to taper the oxycodone hydrochloride tablets dose, rather than abruptly discontinue it, due to the risk of precipitating withdrawal symptoms. Their physician can provide a dose schedule to accomplish a gradual discontinuation of the medication. Drug Interactions Oxycodone is metabolized in part to oxymorphone via the cytochrome p450 isoenzyme CYP2D6. While this pathway may be blocked by a variety of drugs (e.g., certain cardiovascular drugs and antidepressants), such blockade has not yet been shown to be of clinical significance with this agent. However, clinicians should be aware of this possible interaction. Neuromuscular Blocking Agents – Oxycodone, as well as other opioid analgesics, may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. CNS Depressants – Patients receiving narcotic analgesics, general anesthetics, phenothiazines, other tranquilizers, sedative-hypnotics or other CNS depressants (including alcohol) concomitantly with oxycodone hydrochloride tablets may exhibit an additive CNS depression. Interactive effects resulting in respiratory depression, hypotension, profound sedation, or coma may result if these drugs are taken in combination with the usual dosage of oxycodone hydrochloride tablets. When such combined therapy is contemplated, the dose of one or both agents should be reduced. Mixed Agonist/Antagonist Opioid Analgesics – Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, butorphanol and buprenorphine) should be administered with caution to patients who have received or are receiving a course of therapy with a pure opioid agonist analgesic such as oxycodone hydrochloride tablets. In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of oxycodone hydrochloride tablets and/or may precipitate withdrawal symptoms in these patients. Monoamine Oxidase Inhibitors (MAOIs) – MAOIs have been reported to intensify the effects of at least one opioid drug causing anxiety, confusion and significant depression of respiration or coma. The use of oxycodone hydrochloride tablets is not recommended for patients taking MAOIs or within 14 days of stopping such treatment. Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term studies have not been performed in animals to evaluate the carcinogenic potential of oxycodone hydrochloride tablets or oxycodone. The possible effects on male or female fertility have not been studied in animals. Oxycodone hydrochloride was genotoxic in an in vitro mouse lymphoma assay in the presence of metabolic activation. […]

Oxycodone hydrochloride tablets have been evaluated in open label clinical trials in patients with cancer and nonmalignant pain. Oxycodone hydrochloride tablets are associated with adverse experiences similar to those seen with other opioids. Serious adverse reactions that may be associated with oxycodone hydrochloride tablets therapy in clinical use are those observed with other opioid analgesics and include: respiratory depression, respiratory arrest, circulatory depression, cardiac arrest, hypotension, and/or shock (see OVERDOSAGE , WARNINGS ). The less severe adverse events seen on initiation of therapy with oxycodone hydrochloride tablets are also typical opioid side effects. These events are dose dependent, and their frequency depends on 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 of these include nausea, constipation, vomiting, headache, and pruritus. In many cases the frequency of adverse events during initiation of opioid therapy may be minimized by careful individualization of starting dosage, slow titration and the avoidance of large rapid swings in plasma concentration of the opioid. Many of these adverse events will abate as therapy is continued and some degree of tolerance is developed, but others may be expected to remain throughout therapy. In all patients for whom dosing information was available (n=191) from the open-label and double-blind studies involving oxycodone hydrochloride tablets, the following adverse events were recorded in patients treated with oxycodone hydrochloride tablets with an incidence ≥ 3%. In descending order of frequency they were: nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence. The following adverse experiences occurred in less than 3% of patients involved in clinical trials with oxycodone: Body as a Whole – abdominal pain, accidental injury, allergic reaction, back pain, chills and fever, fever, flu syndrome, infection, neck pain, pain, photosensitivity reaction, and sepsis. Cardiovascular – deep thrombophlebitis, heart failure, hemorrhage, hypotension, migraine, palpitation, and tachycardia. Digestive – anorexia, diarrhea, dyspepsia, dysphagia, gingivitis, glossitis, and nausea and vomiting. Hemic and Lymphatic – anemia and leukopenia. Metabolic and Nutritional – edema, gout, hyperglycemia, iron deficiency anemia and peripheral edema. Musculoskeletal – arthralgia, arthritis, bone pain, myalgia and pathological fracture. Nervous – agitation, anxiety, confusion, dry mouth, hypertonia, hypesthesia, nervousness, neuralgia, personality disorder, tremor, and vasodilation. Respiratory – bronchitis, cough increased, dyspnea, epistaxis, laryngismus, lung disorder, pharyngitis, rhinitis, and sinusitis. Skin and Appendages – herpes simplex, rash, sweating, and urticaria. Special Senses – amblyopia. Urogenital – urinary tract infection.