Included as part of the PRECAUTIONS section.
Respiratory depression is the primary risk of OXECTA.
Respiratory depression occurs more frequently in elderly or debilitated
patients, in those suffering from conditions accompanied by hypoxia,
hypercapnia, or upper airway obstruction, or following large initial doses of
opioids given to non-tolerant patients, or when opioids are given in
conjunction with other agents that depress respiration (e.g., benzodiazepines,
tricyclic antidepressants, and sedative-hypnotics).
OXECTA must be used with extreme caution in patients with
chronic obstructive pulmonary disease or cor pulmonale, and in patients having
substantially decreased respiratory reserve (e.g., severe kyphoscoliosis),
hypoxia, hypercapnia, or pre-existing respiratory depression. In such patients,
even usual therapeutic doses of OXECTA may decrease respiratory drive to the
point of apnea. In these patients, alternative non-opioid analgesics should be
considered, and opioids must be employed only under careful medical supervision
at the lowest effective dose.
Misuse And Abuse Of Opioids
OXECTA contains oxycodone HCl, an opioid agonist and a
Schedule II controlled substance. Such drugs are sought by drug abusers and
people with addiction disorders.
OXECTA can be abused in a manner similar to other opioid
agonists, legal or illicit. This should be considered when prescribing or
dispensing oxycodone HCl in situations where the physician or pharmacist is
concerned about an increased risk of misuse or abuse.
OXECTA may be abused by crushing, chewing, snorting or
injecting the product. These practices pose a significant risk to the abuser
that could result in overdose and death [see Drug Abuse And Dependence].
Concerns about abuse and addiction should not prevent the
proper management of pain. Healthcare professionals should contact their State
Professional Licensing Board or State Controlled Substances Authority for
information on how to prevent and detect abuse or misuse of this product.
Central Nervous System Depressants
Patients receiving narcotic analgesics, general
anesthetics, phenothiazines, benzodiazepines, other tranquilizers,
sedative-hypnotics, or other central nervous system depressants concomitantly
with OXECTA may exhibit an additive central nervous system 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 OXECTA. When such combined therapy is contemplated, the dose of
one or both agents should be reduced.
Patients should not consume alcoholic beverages, or any
medications containing alcohol while taking OXECTA.
Head Injury And Increased Intracranial Pressure
In the presence of head injury, intracranial lesions or a
preexisting increase in intracranial pressure, the possible respiratory
depressant effects of OXECTA and its potential to elevate cerebrospinal fluid
pressure (resulting from vasodilation following CO2 retention) may be markedly
exaggerated. Furthermore, OXECTA can produce effects on pupillary response and
consciousness, which may obscure neurologic signs of further increases in
intracranial pressure in patients with head injuries.
OXECTA may cause severe hypotension in patients whose
ability to maintain blood pressure has been compromised by a depleted intravascular
volume, or after concurrent administration with drugs such as phenothiazines,
general anesthetics or other agents which compromise vasomotor tone. OXECTA may
produce orthostatic hypotension in ambulatory patients. OXECTA must be
administered with caution to patients in circulatory shock, since vasodilation
produced by the drug may further reduce cardiac output and blood pressure.
Do not administer OXECTA to patients with
gastrointestinal obstruction, especially paralytic ileus because oxycodone HCl
diminishes propulsive peristaltic waves in the gastrointestinal tract and may
prolong the obstruction.
The administration of OXECTA may obscure the diagnosis or
clinical course in patients with acute abdominal condition.
Use In Pancreatic/Biliary Tract Disease
Use OXECTA with caution in patients with biliary tract
disease, including acute pancreatitis, as oxycodone HCl may cause spasm of the
sphincter of Oddi and diminish biliary and pancreatic secretions.
Special Risk Groups
Use OXECTA with caution and in reduced dosages in
patients with severe renal or hepatic impairment, Addison's disease,
hypothyroidism, prostatic hypertrophy, or urethral stricture, and in elderly or
debilitated patients [see Use In Specific Populations].
Exercise caution in the administration of OXECTA to
patients with CNS depression, toxic psychosis, acute alcoholism and delirium
tremens. All opioids may aggravate convulsions in patients with convulsive
disorders, and all opioids may induce or aggravate seizures in some clinical
Keep OXECTA out of the reach of children. In case of
accidental ingestion, seek emergency medical help immediately.
Driving And Operating Machinery
OXECTA may impair the mental and/or physical abilities
required for the performance of potentially hazardous tasks such as driving a
car or operating heavy machinery. The patient using OXECTA must be cautioned
accordingly [see DRUG INTERACTIONS].
Cytochrome P450 3A4 Inhibitors And Inducers
Since the CYP3A4 isoenzyme plays a major role in the
metabolism of oxycodone, drugs that alter CYP3A4 activity may cause changes in
clearance of oxycodone which could lead to changes in oxycodone plasma
concentrations. The expected clinical results with CYP3A4 inhibitors would be
an increase in oxycodone plasma concentrations and possibly increased or
prolonged opioid effects. The expected clinical results with CYP3A4 inducers
would be 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 oxycodone 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].
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Studies of oxycodone HCl to evaluate its carcinogenic
potential have not been conducted.
Oxycodone HCl was genotoxic in an in vitro mouse lymphoma
assay in the presence of metabolic activation. There was no evidence of
genotoxic potential in an in vitro bacterial reverse mutation assay (Salmonella
typhimurium and Escherichia coli) and in an assay for chromosomal aberrations
(in vivo mouse bone marrow micronucleus assay).
Impairment of Fertility
The potential effects of oxycodone on male and female
fertility have not been evaluated.
Use In Specific Populations
Teratogenic Effects - Pregnancy Category B
There are no adequate and well-controlled studies of oxycodone
use during pregnancy. Based on limited human data in the literature, oxycodone
does not appear to increase the risk of congenital malformations. Animal
reproduction studies have not revealed evidence of teratogenicity or fetal
harm. Because animal reproduction studies are not always predictive of human
response, OXECTA should be used during pregnancy only if clearly needed.
Reproduction studies in Sprague-Dawley rats and New
Zealand rabbits revealed that when oxycodone was administered orally at doses
up to 16 mg/kg and 25 mg/kg (approximately 2 and 5 times the daily oral dose of
90 mg on a mg/m² basis) respectively, it was not teratogenic or
Neonates whose mothers have taken oxycodone chronically
may exhibit respiratory depression and/or withdrawal symptoms, either at birth
and/or in the nursery.
Labor And Delivery
Opioids cross the placenta and may produce respiratory depression
and psycho-physiologic effects in neonates. OXECTA is not recommended for use
in women during or immediately prior to labor. Occasionally, opioid analgesics
may prolong labor through actions which temporarily reduce the strength,
duration, and frequency of uterine contractions. Neonates, whose mothers
received opioid analgesics during labor, must be observed closely for signs of
respiratory depression. A specific narcotic antagonist, naloxone, must be
available for reversal of narcotic-induced respiratory depression in the
Low levels of oxycodone have been detected in maternal
milk. The amount of oxycodone delivered to the infant depends on the plasma
concentration of the mother, the amount of milk ingested by the infant, and the
extent of first-pass metabolism. There is potential for serious adverse
reactions in nursing infants from oxycodone that includes respiratory
depression, sedation and potentially withdrawal symptoms when the mother stops
taking oxycodone HCl. As such, one should consider either discontinuing nursing
or discontinuing the drug, while taking into account the importance of the drug
to the mother.
The safety, effectiveness, and pharmacokinetics of OXECTA
in pediatric patients below the age of 18 have not been established.
Elderly patients (aged 65 years or older) may have
increased sensitivity to OXECTA. Use caution when selecting a dose for an
elderly patient, usually starting at the low end of the dosing range,
reflecting the greater frequency of decreased hepatic, renal, or cardiac
function, concomitant disease, and use of other drug therapy.
Since oxycodone is extensively metabolized in the liver,
its clearance may decrease in patients with hepatic impairment. Follow a
conservative approach to initiate dosing in patients with hepatic impairment.
Monitor patients closely and adjust the dose based on clinical response [see DOSAGE
Information from oxycodone HCl indicates that patients
with renal impairment (defined as a creatinine clearance < 60 mL/min) had
higher plasma concentrations of oxycodone than subjects with normal renal
function. Use a conservative approach to initiate dosing in patients with renal
impairment. Monitor patients closely and adjust the dose based on clinical
response [see DOSAGE AND ADMINISTRATION].