"Nov. 2, 2012 -- Safety steps taken in the wake of the fungal meningitis outbreak have worsened drug shortages, raising questions about whether the U.S. must choose between the safety and the availability of crucial medicines.
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in 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 clinical practice.
Serious adverse reactions that may be associated with OXECTA include: respiratory depression, respiratory arrest, circulatory depression, cardiac arrest, hypotension, and/or shock [see WARNINGS AND PRECAUTIONS and OVERDOSAGE].
The common adverse reactions seen on initiation of therapy with OXECTA 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 therapy. The most frequent of the adverse reactions include nausea, constipation, vomiting, headache, and pruritus.
The frequency of adverse reactions 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 reactions 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 open-label and double-blind studies involving oxycodone, the following adverse reactions were recorded in oxycodone-treated patients with an incidence of ≥ 3%. In descending order of frequency they were: nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence.
The following adverse reactions occurred in less than 3% of patients involved in clinical trials with oxycodone:
Special Senses: amblyopia.
Urogenital: urinary tract infection.
Read the Oxecta (oxycodone hcl, usp tablets) Side Effects Center for a complete guide to possible side effects »
Central Nervous System Depressants
Other central nervous system (CNS) depressants including sedatives, hypnotics, general anesthetics, antiemetics, phenothiazines, other tranquilizers, and alcohol increase the risk of respiratory depression, hypotension, profound sedation, or coma. Use OXECTA with caution and in reduced dosages in patients taking these agents.
Patients should not consume alcoholic beverages, or any medications containing alcohol while taking OXECTA.
Mixed Agonist/Antagonist Opioid Analgesics
Do not administer mixed agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, butorphanol and buprenorphine) to patients who have received or are receiving a course of therapy with a pure opioid agonist analgesic such as oxycodone HCl. In these patients, mixed agonist/antagonist analgesics may reduce the analgesic effect of oxycodone HCl and/or may precipitate withdrawal symptoms.
Monoamine Oxidase Inhibitors (MAOIs)
Monoamine oxidase inhibitors 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 OXECTA is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.
Agents Affecting Cytochrome P450 Enzymes
A published study showed that the co-administration with voriconazole, a CYP3A4 inhibitor, significantly increased the plasma concentrations of oxycodone. 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 prolong opioid effects. If co-administration is necessary, caution is advised when initiating therapy with, currently taking, or discontinuing CYP3A4 inhibitors. Evaluate these patients at frequent intervals and consider dose adjustments until stable drug effects are achieved [see CLINICAL PHARMACOLOGY].
A published study showed that the co-administration of rifampin, a drug metabolizing enzyme inducer, significantly decreased plasma oxycodone concentrations. Induction of CYP3A4 activity by its inducers, such as rifampin, carbamazepine, and phenytoin, may lead to a 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 therapy with, currently taking, or discontinuing CYP3A4 inducers. Evaluate these patients at frequent intervals and consider dose adjustments until stable drug effects are achieved [see CLINICAL PHARMACOLOGY].
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, including amiodarone and quinidine, 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.
Anticholinergics or other medications with anticholinergic activity when used concurrently with opioid analgesics may result in increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Drug Abuse And Dependence
OXECTA contains oxycodone HCl, a mu-agonist opioid of the morphine type and a Schedule II controlled substance. OXECTA, like other opioids used in analgesia, can be abused and is subject to criminal diversion.
Abuse of OXECTA poses a hazard of overdose and death. This risk is increased with concurrent abuse of alcohol or other substances.
“Drug-seeking” behavior is very common in persons with substance abuse disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “Doctor shopping” to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction.
Abuse and addiction are separate and distinct from physical dependence and tolerance. Drug addiction is characterized by compulsive use, use for non-medical purposes, and continued use despite harm or risk of harm. Drug addiction is a treatable disease, utilizing a multi-disciplinary approach, but relapse is common. Healthcare providers should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence. The converse is also true. In addition, abuse of opioids can occur in the absence of true addiction and is characterized by intentional nontherapeutic use of a drug for its rewarding psychological or physiological effects, often in combination with other psychoactive substances. Misuse includes use of a drug in ways other than prescribed or directed by a healthcare provider. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised.
OXECTA is intended for oral use only. Abuse of OXECTA poses a risk of overdose and death. The risk of overdose and death is increased with concurrent abuse of alcohol or other central nervous system depressants. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.
In a double-blind, active-comparator, crossover study in 40 non-dependent recreational opioid users, “drug liking” responses and single-dose safety of crushed OXECTA tablets were compared with crushed immediate-release Oxycodone tablets when subjects self-administered the drug intranasally. The presence of sequence effects resulted in questionable reliability of the second period data. First period data demonstrated small numeric differences in the median and mean drug liking scores, lower in response to OXECTA than immediate-release oxycodone. Thirty percent of subjects exposed to OXECTA responded that they would not take the drug again compared to 5% of subjects exposed to immediate-release oxycodone. Study subjects self-administering OXECTA reported a higher incidence of nasopharyngeal and facial adverse events and a decreased ability to completely insufflate two crushed tablets within a fixed time period (21 of 40 subjects). The clinical significance of the difference in drug liking and difference in response to taking the drug again reported in this study has not yet been established. There is no evidence that OXECTA has a reduced abuse liability compared to immediate-release oxycodone.
Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.
Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms.
Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Physical dependence is manifested by withdrawal symptoms after abrupt discontinuation of a drug or upon administration of an antagonist. Physical dependence and tolerance are not unusual during chronic opioid therapy.
The opioid abstinence or withdrawal syndrome is characterized by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. In general, opioids should not be abruptly discontinued.
Last reviewed on RxList: 6/14/2013
This monograph has been modified to include the generic and brand name in many instances.
Additional Oxecta Information
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