Oxycodone Hydrochloride (Page 4 of 10)

5.8 Adrenal Insufficiency

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

5.9 Severe Hypotension

Oxycodone HCl may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Drug Interactions (7)]. Monitor these patients for signs of hypotension after initiating or titrating the dosage of oxycodone HCl. In patients with circulatory shock, use of oxycodone HCl may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid use of oxycodone HCl in patients with circulatory shock.

5.10 Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness

In patients who may be susceptible to the intracranial effects of CO₂ retention (e.g., those with evidence of increased intracranial pressure or brain tumors), oxycodone HCl may reduce the respiratory drive, and the resultant CO₂ retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with oxycodone HCl.

Opioids may obscure the clinical course in a patient with a head injury. Avoid the use of oxycodone HCl in patients with impaired consciousness or coma.

5.11 Risks of Use in Patients with Gastrointestinal Conditions

Oxycodone HCl is contraindicated in patients with gastrointestinal obstruction, including paralytic ileus.

The oxycodone in oxycodone HCl tablets may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

5.12 Increased Risk of Seizures in Patients with Seizure Disorders

The oxycodone in oxycodone HCl may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during oxycodone HCl therapy.

5.13 Withdrawal

Do not abruptly discontinue oxycodone HCl in a patient physically dependent on opioids. When discontinuing oxycodone HCl in a physically dependent patient, gradually taper the dosage. Rapid tapering of oxycodone in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain [see Dosage and Administration (2.4), Drug Abuse and Dependence (9.3)].

Additionally, avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including oxycodone HCl. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms [see Drug Interactions (7)].

5.14 Risks of Driving and Operating Machinery

Oxycodone HCl may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of oxycodone HCl and know how they will react to the medication [see Patient Counseling Information (17)].

6 ADVERSE REACTIONS

The following serious adverse reactions are described, or described in greater detail, in other sections:

•

Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1)]

•

Life-Threatening Respiratory Depression [see Warnings and Precautions (5.3)]

•

Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.4)]

•

Interactions with Benzodiazepines or Other CNS Depressants [see Warnings and Precautions (5.6)]

•

Adrenal Insufficiency [see Warnings and Precautions (5.8)]

•

Severe Hypotension [see Warnings and Precautions (5.9)]

•

Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.11)]

•

Seizures [see Warnings and Precautions (5.12)]

•

Withdrawal [see Warnings and Precautions (5.13)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Oxycodone HCl tablets have been evaluated in open label clinical trials in patients with cancer and nonmalignant pain. Oxycodone HCl tablets are associated with adverse experiences similar to those seen with other opioids.

Serious adverse reactions associated with oxycodone HCl use included: respiratory depression, respiratory arrest, circulatory depression, cardiac arrest, hypotension, and/or shock.

The common adverse reactions seen on initiation of therapy with oxycodone HCl are dose related and are typical opioid-related adverse reactions. The most frequent of these included nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence. The frequency of these reactions depended on several factors, including clinical setting, the patient’s level of opioid tolerance, and host factors specific to the individual.

In all patients for whom dosing information was available (n=191) from the open-label and double-blind studies involving oxycodone HCl, the following adverse events were recorded in oxycodone HCl treated patients with an incidence ≥ 3%. In descending order of frequency they were: nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence.

Other less frequently observed adverse reactions from opioid analgesics, including oxycodone HCl included:

Blood and lymphatic system disorders: anemia, leukopenia

Cardiac disorders: cardiac failure, palpitation, tachycardia

Gastrointestinal disorders: abdominal pain, dry mouth, diarrhea, dyspepsia, dysphagia, glossitis, nausea, vomiting

General disorders and administration site conditions: chills, edema, edema peripheral, pain, pyrexia

Immune system disorders: hypersensitivity

Infections and infestations: bronchitis, gingivitis, infection, pharyngitis, rhinitis, sepsis, sinusitis, urinary tract infection

Injury, poisoning and procedural complications: injury

Metabolism and nutrition disorders: decreased appetite, gout, hyperglycemia

Musculoskeletal and connective tissue disorders: arthralgia, arthritis, back pain, bone pain, myalgia, neck pain, pathological fracture

Nervous system disorders: hypertonia, hypoesthesia, migraine, neuralgia, tremor, vasodilation

Psychiatric disorders: agitation, anxiety, confusional state, nervousness, personality disorder

Respiratory, thoracic and mediastinal disorders: cough, dyspnea, epistaxis, laryngospasm, lung disorder

Skin and subcutaneous tissue disorders: photosensitivity reaction, rash, hyperhidrosis, urticaria

Vascular disorders: thrombophlebitis, hemorrhage, hypotension, vasodilatation