"Nov. 1, 2012 -- Two more drugs made by the New England Compounding Center (NECC) are crawling with various kinds of bacteria, FDA tests reveal.
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Addiction, Abuse, And Misuse
OXYCONTIN contains oxycodone, a Schedule II controlled substance. As an opioid, OXYCONTIN exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence]. As modified-release products such as OXYCONTIN deliver the opioid over an extended period of time, there is a greater risk for overdose and death due to the larger amount of oxycodone present [see Drug Abuse and Dependence].
Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed OXYCONTIN. Addiction can occur at recommended doses and if the drug is misused or abused.
Assess each patient's risk for opioid addiction, abuse or misuse prior to prescribing OXYCONTIN, and monitor all patients receiving OXYCONTIN for the development of these behaviors or conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed modified-release opioid formulations such as OXYCONTIN, but use in such patients necessitates intensive counseling about the risks and proper use of OXYCONTIN along with intensive monitoring for signs of addiction, abuse, and misuse.
Abuse, or misuse of OXYCONTIN by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of oxycodone and can result in overdose and death [see OVERDOSAGE].
Opioid agonists are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing OXYCONTIN. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see PATIENT INFORMATION]. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression has been reported with the use modified-release opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status [see OVERDOSAGE]. Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of OXYCONTIN, the risk is greatest during the initiation of therapy or following a dose increase. Closely monitor patients for respiratory depression when initiating therapy with OXYCONTIN and following dose increases.
To reduce the risk of respiratory depression, proper dosing and titration of OXYCONTIN are essential [see DOSAGE AND ADMINISTRATION]. Overestimating the OXYCONTIN dose when converting patients from another opioid product can result in a fatal overdose with the first dose.
Accidental ingestion of even one dose of OXYCONTIN, especially by children, can result in respiratory depression and death due to an overdose of oxycodone.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of OXYCONTIN during pregnancy can result in withdrawal signs in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn.
Interactions With Central Nervous System Depressants
Hypotension and profound sedation, coma, or respiratory depression may result if OXYCONTIN is used concomitantly with other central nervous system (CNS) depressants (e.g., sedatives, anxiolytics, hypnotics, neuroleptics, other opioids).
When considering the use of OXYCONTIN in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient's response, including the degree of tolerance that has developed to CNS depression. Additionally, evaluate the patient's use of alcohol or illicit drugs that can cause CNS depression. If the decision to begin OXYCONTIN therapy is made, start with 1/3 to ½ the usual dose of OXYCONTIN, monitor patients for signs of sedation and respiratory depression and consider using a lower dose of the concomitant CNS depressant [see DRUG INTERACTIONS and DOSAGE AND ADMINISTRATION].
Use In Elderly, Cachectic, And Debilitated Patients
Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients. Monitor such patients closely, particularly when initiating and titrating OXYCONTIN and when OXYCONTIN is given concomitantly with other drugs that depress respiration [see Life-Threatening Respiratory Depression].
Use In Patients With Chronic Pulmonary Disease
Monitor patients with significant chronic obstructive pulmonary disease or cor pulmonale, and patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression for respiratory depression, particularly when initiating therapy and titrating with OXYCONTIN, as in these patients, even usual therapeutic doses of OXYCONTIN may decrease respiratory drive to the point of apnea [see Life-Threatening Respiratory Depression]. Consider the use of alternative non-opioid analgesics in these patients if possible.
OXYCONTIN may cause severe hypotension, including orthostatic hypotension and syncope in ambulatory patients. There is an 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]. Monitor these patients for signs of hypotension after initiating or titrating the dose of OXYCONTIN. In patients with circulatory shock, OXYCONTIN may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of OXYCONTIN in patients with circulatory shock.
Use In Patients With Head Injury Or Increased Intracranial Pressure
Monitor patients taking OXYCONTIN who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors) for signs of sedation and respiratory depression, particularly when initiating therapy with OXYCONTIN. OXYCONTIN may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Opioids may also obscure the clinical course in a patient with a head injury.
Avoid the use of OXYCONTIN in patients with impaired consciousness or coma.
Difficulty In Swallowing And Risk For Obstruction In Patients At Risk For A Small Gastrointestinal Lumen
There have been post-marketing reports of difficulty in swallowing OXYCONTIN tablets. These reports included choking, gagging, regurgitation and tablets stuck in the throat. Instruct patients not to pre-soak, lick or otherwise wet OXYCONTIN tablets prior to placing in the mouth, and to take one tablet at a time with enough water to ensure complete swallowing immediately after placing in the mouth.
There have been rare post-marketing reports of cases of intestinal obstruction, and exacerbation of diverticulitis, some of which have required medical intervention to remove the tablet. Patients with underlying GI disorders such as esophageal cancer or colon cancer with a small gastrointestinal lumen are at greater risk of developing these complications. Consider use of an alternative analgesic in patients who have difficulty swallowing and patients at risk for underlying GI disorders resulting in a small gastrointestinal lumen.
Use In Patients With Gastrointestinal Conditions
OXYCONTIN is contraindicated in patients with GI obstruction, including paralytic ileus. The oxycodone in OXYCONTIN may cause spasm of the sphincter of Oddi. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. Opioids may cause increases in the serum amylase.
Use In Patients With Convulsive Or Seizure Disorders
The oxycodone in OXYCONTIN may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings. Monitor patients with a history of seizure disorders for worsened seizure control during OXYCONTIN therapy.
Avoidance Of Withdrawal
Avoid the use of mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) or partial agonist (buprenorphine) analgesics in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic, including OXYCONTIN. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or may precipitate withdrawal symptoms.
When discontinuing OXYCONTIN, gradually taper the dose [see DOSAGE AND ADMINISTRATION]. Do not abruptly discontinue OXYCONTIN.
Driving And Operating Machinery
OXYCONTIN 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 OXYCONTIN and know how they will react to the medication.
Cytochrome P450 3A4 Inhibitors And Inducers
Since the CYP3A4 isoenzyme plays a major role in the metabolism of OXYCONTIN, drugs that alter CYP3A4 activity may cause changes in clearance of oxycodone which could lead to changes in oxycodone plasma concentrations.
Inhibition of CYP3A4 activity by its inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of oxycodone and prolong opioid effects.
CYP450 inducers, such as rifampin, carbamazepine, and phenytoin, may induce the metabolism of oxycodone and, therefore, may cause increased clearance of the drug which could lead to a decrease in oxycodone plasma concentrations, lack of efficacy or, possibly, development of an abstinence syndrome in a patient who had developed physical dependence to oxycodone.
If co-administration is necessary, caution is advised when initiating OXYCONTIN treatment in patients currently taking, or discontinuing, CYP3A4 inhibitors or inducers. Evaluate these patients at frequent intervals and consider dose adjustments until stable drug effects are achieved [see DRUG INTERACTIONS and CLINICAL PHARMACOLOGY].
Not every urine drug test for “opioids” or “opiates” detects oxycodone reliably, especially those designed for in-office use. Further, many laboratories will report urine drug concentrations below a specified “cut-off” value as “negative”. Therefore, if urine testing for oxycodone is considered in the clinical management of an individual patient, ensure that the sensitivity and specificity of the assay is appropriate, and consider the limitations of the testing used when interpreting results.
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Addiction, Abuse and Misuse
Inform patients that the use of OXYCONTIN, even when taken as recommended can result in addiction, abuse and misuse, which can lead to overdose and death [see WARNINGS AND PRECAUTIONS]. Instruct patients not to share OXYCONTIN with others and to take steps to protect OXYCONTIN from theft or misuse.
Life-Threatening Respiratory Depression
Inform patients of the risk of life-threatening respiratory depression including information that the risk is greatest when starting OXYCONTIN or when the dose is increased and that it can occur even at recommended doses [see WARNINGS AND PRECAUTIONS]. Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop.
Inform patients that accidental ingestion, especially in children, may result in respiratory depression or death [see WARNINGS AND PRECAUTIONS]. Instruct patients to take steps to store OXYCONTIN securely and to dispose of unused OXYCONTIN by flushing the tablets down the toilet.
Neonatal Opioid Withdrawal Syndrome
Inform female patients of reproductive potential that prolonged use of OXYCONTIN during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated [see WARNINGS AND PRECAUTIONS].
Interactions with Alcohol and other CNS Depressants
Inform patients that potentially serious additive effects may occur if OXYCONTIN is used with other CNS depressants, and not to use such drugs unless supervised by a health care provider.
Important Administration Instructions
Instruct patients how to properly take OXYCONTIN, including the following:
- OXYCONTIN is designed to work properly only if swallowed intact. Taking cut, broken, chewed, crushed, or dissolved OXYCONTIN tablets can result in a fatal overdose.
- OXYCONTIN tablets should be taken one tablet at a time.
- Do not pre-soak, lick or otherwise wet the tablet prior to placing in the mouth.
- Take each tablet with enough water to ensure complete swallowing immediately after placing in the mouth.
Inform patients that OXYCONTIN may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position).
Driving or Operating Heavy Machinery
Inform patients that OXYCONTIN may impair the ability to perform potentially hazardous activities such as driving a car or operating heavy machinery. Advise patients not to perform such tasks until they know how they will react to the medication.
Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention.
Inform patients that anaphylaxis has been reported with ingredients contained in OXYCONTIN. Advise patients how to recognize such a reaction and when to seek medical attention.
Advise female patients that OXYCONTIN can cause fetal harm and to inform the prescriber if they are pregnant or plan to become pregnant.
Disposal of Unused Oxycontin
Advise patients to flush the unused tablets down the toilet when OXYCONTIN is no longer needed.
Healthcare professionals can telephone Purdue Pharma's Medical Services Department (1-888726-7535) for information on this product.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
No animal studies to evaluate the carcinogenic potential of oxycodone have been conducted.
Oxycodone was genotoxic in the mouse lymphoma assay at concentrations of 50 mcg/mL or greater with metabolic activation and at 400 mcg/mL or greater without metabolic activation. Clastogenicity was observed with oxycodone in the presence of metabolic activation in one chromosomal aberration assay in human lymphocytes at concentrations greater than or equal to 1250 mcg/mL at 24 but not 48 hours of exposure. In a second chromosomal aberration assay with human lymphocytes, no structural clastogenicity was observed either with or without metabolic activation; however, in the absence of metabolic activation, oxycodone increased numerical chromosomal aberrations (polyploidy). Oxycodone was not genotoxic in the following assays: Ames S. typhimurium and E. coli test with and without metabolic activation at concentrations up to 5000 μg/plate, chromosomal aberration test in human lymphocytes (in the absence of metabolic activation) at concentrations up to 1500 μg/mL, and with activation after 48 hours of exposure at concentrations up to 5000 μg/mL, and in the in vivo bone marrow micronucleus assay in mice (at plasma levels up to 48 μg/mL).
Impairment of Fertility
In a study of reproductive performance, rats were administered a once daily gavage dose of the vehicle or oxycodone hydrochloride (0.5, 2, and 8 mg/kg). Male rats were dosed for 28 days before cohabitation with females, during the cohabitation and until necropsy (2-3 weeks post-cohabitation). Females were dosed for 14 days before cohabitation with males, during cohabitation and up to gestation day 6. Oxycodone hydrochloride did not affect reproductive function in male or female rats at any dose tested ( ≤ 8 mg/kg/day).
Use In Specific Populations
Fetal/neonatal Adverse Reactions
Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Observe newborns for symptoms of neonatal opioid withdrawal syndrome, such as poor feeding, diarrhea, irritability, tremor, rigidity, and seizures, and manage accordingly [see WARNINGS AND PRECAUTIONS].
Teratogenic Effects -Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. OXYCONTIN should be used during pregnancy only if the potential benefit justifies the risk to the fetus.
The effect of oxycodone in human reproduction has not been adequately studied. Studies with oral doses of oxycodone hydrochloride in rats up to 8 mg/kg/day and rabbits up to 125 mg/kg/day, equivalent to 0.5 and 15 times an adult human dose of 160 mg/day, respectively on a mg/m² basis, did not reveal evidence of harm to the fetus due to oxycodone. In a pre-and postnatal toxicity study, female rats received oxycodone during gestation and lactation. There were no long-term developmental or reproductive effects in the pups [see Nonclinical Toxicology].
Oxycodone hydrochloride was administered orally to female rats during gestation and lactation in a pre-and postnatal toxicity study. There were no drug-related effects on reproductive performance in these females or any long-term developmental or reproductive effects in pups born to these rats. Decreased body weight was found during lactation and the early post-weaning phase in pups nursed by mothers given the highest dose used (6 mg/kg/day, equivalent to approximately 0.4-times an adult human dose of 160 mg/day, on a mg/m² basis). However, body weight of these pups recovered.
Labor And Delivery
Opioids cross the placenta and may produce respiratory depression in neonates. OXYCONTIN is not recommended for use in women immediately prior to labor, when use of shorter-acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics can prolong labor through actions which temporarily reduce the strength, duration and frequency of uterine contractions. However this effect is not consistent and may be offset by an increased rate of cervical dilatation, which tends to shorten labor.
Oxycodone has been detected in breast milk. Instruct patients not to undertake nursing while receiving OXYCONTIN. Do not initiate OXYCONTIN therapy while nursing because of the possibility of sedation or respiratory depression in the infant.
Withdrawal signs can occur in breast-fed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.
Safety and effectiveness of OXYCONTIN in pediatric patients below the age of 18 years have not been established.
In controlled pharmacokinetic studies in elderly subjects (greater than 65 years) the clearance of oxycodone was slightly reduced. Compared to young adults, the plasma concentrations of oxycodone were increased approximately 15% [see CLINICAL PHARMACOLOGY]. Of the total number of subjects (445) in clinical studies of oxycodone hydrochloride controlled-release tablets, 148 (33.3%) were age 65 and older (including those age 75 and older) while 40 (9.0%) were age 75 and older. In clinical trials with appropriate initiation of therapy and dose titration, no untoward or unexpected adverse reactions were seen in the elderly patients who received oxycodone hydrochloride controlled-release tablets. Thus, the usual doses and dosing intervals may be appropriate for elderly patients. However, reduce the starting dose to 1/3 to ½ the usual dosage in debilitated, non-opioid-tolerant patients. Respiratory depression is the chief risk in elderly or debilitated patients, usually the result of large initial doses in patients who are not tolerant to opioids, or when opioids are given in conjunction with other agents that depress respiration. Titrate the dose of OXYCONTIN cautiously in these patients.
A study of OXYCONTIN in patients with hepatic impairment demonstrated greater plasma concentrations than those seen at equivalent doses in persons with normal hepatic function. Therefore, in the setting of hepatic impairment, start dosing patients at 1/3 to ½ the usual starting dose followed by careful dose titration [see CLINICAL PHARMACOLOGY].
In patients with renal impairment, as evidenced by decreased creatinine clearance ( < 60 mL/min), the concentrations of oxycodone in the plasma are approximately 50% higher than in subjects with normal renal function. Follow a conservative approach to dose initiation and adjust according to the clinical situation [see CLINICAL PHARMACOLOGY].
In pharmacokinetic studies with OXYCONTIN, opioid-na´ve females demonstrate up to 25% higher average plasma concentrations and greater frequency of typical opioid adverse events than males, even after adjustment for body weight. The clinical relevance of a difference of this magnitude is low for a drug intended for chronic usage at individualized dosages, and there was no male/female difference detected for efficacy or adverse events in clinical trials.
Last reviewed on RxList: 4/30/2014
This monograph has been modified to include the generic and brand name in many instances.
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