OXYCODONE AND ACETAMINOPHEN
Oxycodone and Acetaminophen is available in tablets for oral administration.
Each tablet for oral administration contains:
Oxycodone Hydrochloride USP……………………………………………………….. 5 mg*
(*5 mg Oxycodone Hydrochloride is equivalent to 4.4815 mg Oxycodone)
Acetaminophen USP…………………………………………………………………… 325 mg
Oxycodone Hydrochloride USP……………………………………………………. 7.5 mg*
(*7.5 mg Oxycodone Hydrochloride is equivalent to 6.7228 mg Oxycodone)
Acetaminophen USP…………………………………………………………………… 325 mg
Oxycodone Hydrochloride USP…………………………………………………….. 10 mg*
(*10 mg Oxycodone Hydrochloride is equivalent to 8.9637 mg Oxycodone)
Acetaminophen USP…………………………………………………………………… 325 mg
The tablets contain: crospovidone, microcrystalline cellulose, povidone, pregelatinized starch, silicon dioxide and stearic acid.
Oxycodone and acetaminophen tablets contain oxycodone, 14-hydroxydihydrocodeinone, a semisynthetic opioid analgesic which occurs as a white to off-white fine crystalline powder. It is derived from the opium alkaloid, thebaine.
Oxycodone and acetaminophen tablets contain acetaminophen, 4′-hydroxyacetanilide, is
a non-opiate, non-salicylate analgesic and antipyretic which occurs as a white, odorless,
Mechanism of Action
Oxycodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, although it can interact with other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with oxycodone. Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression.
The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.
The precise mechanism of the analgesic properties of acetaminophen is not established
but is thought to involve central actions.
INDICATIONS AND USAGE
Oxycodone and acetaminophen tablets are indicated for the management of pain severe
enough to require an opioid analgesic and for which alternative treatments are
Limitations of Use:
Because of the risks of addiction, abuse, and misuse, with opioids, even at recommended doses, reserve oxycodone and acetaminophen tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics)
- Have not been tolerated, or are not expected to be tolerated,
- Have not provided adequate analgesia, or are not expected to provide adequate analgesia.
Oxycodone and acetaminophen tablets are contraindicated in patients with:
- Significant respiratory depression
- Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
- Known or suspected gastrointestinal obstruction, including paralytic ileus
- Hypersensitivity to oxycodone, acetaminophen, or any other component of the product (e.g., anaphylaxis)
Addiction, Abuse, and Misuse
Oxycodone and acetaminophen tablets contain oxycodone, a Schedule II controlled substance. As an opioid, oxycodone and acetaminophen tablets expose users to the risks of addiction, abuse, and misuse.
Although the risk of addiction in any individual is unknown, it can occur in patients
appropriately prescribed oxycodone and acetaminophen tablets. Addiction can occur at
recommended dosages and if the drug is misused or abused.
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression has been reported with the use
of 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.
Carbon dioxide (CO2 ) retention from opioid-induced respiratory depression can
exacerbate the sedating effects of opioids.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of oxycodone and acetaminophen tablets during pregnancy can result in
withdrawal 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.
Observe newborns for signs of neonatal opioid withdrawal syndrome and manage
Advise pregnant women using opioids for a prolonged period of the risk of
neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be
Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4
Inhibitors and Inducers
Concomitant use of oxycodone and acetaminophen tablets with a CYP3A4 inhibitor,
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 hydrochloride and prolong opioid adverse reactions, which
may cause potentially fatal respiratory depression, particularly when
an inhibitor is added after a stable dose of oxycodone and acetaminophen tablets is
Similarly, discontinuation of a CYP3A4 inducer, such as rifampin,
carbamazepine, and phenytoin, in oxycodone and acetaminophen tablets-treated
patients may increase oxycodone plasma concentrations and prolong opioid adverse
reactions. When using oxycodone and acetaminophen tablets with CYP3A4 inhibitors or
discontinuing CYP3A4 inducers in oxycodone and acetaminophen tablets-treated
patients, monitor patients closely at frequent intervals and consider dosage reduction of
oxycodone and acetaminophen tablets until stable drug effects are achieved
Risks from Concomitant Use with Benzodiazepines or Other CNS
Profound sedation, respiratory depression, coma, and death may result from the
concomitant use of oxycodone and acetaminophen tablets with benzodiazepines or
other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics,
tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids,
alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use
in patients for whom alternative treatment options are inadequate.
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.
Oxycodone and acetaminophen tablets 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).
Monitor these patients for signs of hypotension after initiating or titrating
the dosage of oxycodone and acetaminophen tablets. In patients with circulatory shock
oxycodone and acetaminophen tablets may cause vasodilatation that can further reduce
cardiac output and blood pressure. Avoid the use of oxycodone and acetaminophen
tablets with circulatory shock.
Acetaminophen has been associated with cases of acute liver failure, at times resulting in
liver transplant and death. Most of the cases of liver injury are associated with the use of
acetaminophen at doses that exceed 4000 milligrams per day, and often involve more
than one acetaminophen-containing product. The excessive intake of acetaminophen
may be intentional to cause self-harm or unintentional as patients attempt to obtain
more pain relief or unknowingly take other acetaminophen-containing products.
The risk of acute liver failure is higher in individuals with underlying liver disease and in
individuals who ingest alcohol while taking acetaminophen.
Instruct patients to look for acetaminophen or APAP on package labels and not to use
more than one product that contains acetaminophen. Instruct patients to seek medical
attention immediately upon ingestion of more than 4000 milligrams of acetaminophen
per day, even if they feel well.
Serious Skin Reactions
Rarely, acetaminophen may cause serious skin reactions such as acute generalized
exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic
epidermal necrolysis (TEN), which can be fatal. Patients should be informed about the
signs of serious skin reactions, and use of the drug should be discontinued at the first
appearance of skin rash or any other sign of hypersensitivity.
There have been postmarketing reports of hypersensitivity and anaphylaxis associated
with use of acetaminophen. Clinical signs included swelling of the face, mouth, and
throat, respiratory distress, urticaria, rash, pruritus, and vomiting. There were
infrequent reports of life-threatening anaphylaxis requiring emergency medical attention.
Instruct patients to discontinue oxycodone and acetaminophen tablets immediately and
seek medical care if they experience these symptoms. Do not prescribe oxycodone and
acetaminophen tablets for patients with acetaminophen allergY.
Risks of Use in Patients with Gastrointestinal Conditions
Oxycodone and acetaminophen tablets are contraindicated in patients with known or
suspected gastrointestinal obstruction, including paralytic ileus.
The administration of oxycodone and acetaminophen tablets, or other opioids may
obscure the diagnosis or clinical course in patients with acute abdominal conditions.
The oxycodone in oxycodone and acetaminophen 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.
Increased Risk of Seizures in Patients with Seizure Disorders
The oxycodone in oxycodone and acetaminophen tablets may increase the frequency of
seizures in patients with seizure disorders, and may increase the risk of seizures
occuring in other clinical settings associated with seizures. Monitor patients with a
history of seizure disorders for worsened seizure control during oxycodone and
acetaminophen tablets therapy.
Do not abruptly discontinue oxycodone and acetaminophen tablets in a patient
physically dependent on opioids. When discontinuing oxycodone and acetaminophen
tablets in a physically dependent patient, gradually taper the dosage. Rapid tapering of
oxycodone and acetaminophen tablets in a patient physically dependent on opioids may
lead to a withdrawal syndrome and return of pain.
Risks of Driving and Operating Machinery
Oxycodone and acetaminophen tablets 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 and acetaminophen tablets and know how they will
react to the medication
Inhibitors of CYP3A4 and CYP2D6: The concomitant use of oxycodone and acetaminophen tablets and CYP3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), can increase the plasma concentration of oxycodone, resulting in increased or prolonged opioid effects. These
effects could be more pronounced with concomitant use of oxycodone and acetaminophen tablets and CYP3A4 and CYP2D6 inhibitors, particularly when an inhibitor is added after a stable dose of oxycodone and acetaminophen tablets is achieved
Inducers of CYP3A4: The concomitant use of oxycodone and acetaminophen tablets and CYP3A4 inducers, such as rifampin, carbamazepine, and phenytoin, can decrease the plasma
concentration of oxycodone, resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to oxycodone and acetaminophen tablets
Benzodiazepines and Other CNS Depressants: Due to additive pharmacologic effect, the concomitant use of benzodiazepines and other CNS depressants such as benzodiazepines and other sedative hypnotics, anxiolytics, and tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.
Serotonergic Drugs: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as selective serotonin reuptake inhibitors (SSRIs),
serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tryptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), and monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue), has resulted in serotonin syndrome
Monoamine Oxidase Inhibitors (MAOIs): The concomitant use of opioids and MAOIs, such as phenelzine, tranylcypromine, linezolid, may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma).
The use of oxycodone and acetaminophen tablets is not recommended for patients
taking MAOIs or within 14 days of stopping such treatment.
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics: The concomitant use of opioids with other opioid analgesics, such as butorphanol, nalbuphine, pentazocine, may reduce the analgesic effect of oxycodone and acetaminophen tablets and/or precipitate withdrawal symptoms. Advise patient to avoid concomitant use of these drugs.
Muscle Relaxants: Oxycodone and acetaminophen tablets may enhance the neuromuscular-blocking action of skeletal muscle relaxants and produce an increase in the degree of respiratory depression.
Diuretics: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic
hormone. If concomitant use is warranted, monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.
Anticholinergic Drugs: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. If concomitant use is warranted, monitor patients for signs of urinary retention or reduced gastric motility when oxycodone and acetaminophen tablets are used concomitantly with anticholinergic drugs.
Alcohol, Ethyl: Hepatotoxicity has occurred in chronic alcoholics following various dose levels
(moderate to excessive) of acetaminophen.
Oral Contraceptives: Increase in glucuronidation resulting in increased plasma clearance and a decreased half-life of acetaminophen.
Charcoal (activated): Reduces acetaminophen absorption when administered as soon as possible after
Beta Blockers (Propranolol): Propranolol appears to inhibit the enzyme systems responsible for the glucuronidation and oxidation of acetaminophen. Therefore, the pharmacologic effects of
acetaminophen may be increased.
Loop Diuretics: The effects of the loop diuretic may be decreased because acetaminophen may
decrease renal prostaglandin excretion and decrease plasma renin activity.
Lamotrigine: Serum lamotrigine concentrations may be reduced, producing a decrease in therapeutic
Probenecid: Probenecid may increase the therapeutic effectiveness of acetaminophen slightly.
Zidovudine: The pharmacologic effects of zidovudine may be decreased because of enhanced non-hepatic or renal clearance of zidovudine.
Drug/Laboratory Test Interactions
Depending on the sensitivity/specificity and the test methodology, the individual
components of oxycodone and acetaminophen tablets may cross-react with assays
used in the preliminary detection of cocaine (primary urinary metabolite,
benzoylecgonine) or marijuana (cannabinoids) in human urine. A more specific alternate
chemical method must be used in order to obtain a confirmed analytical result. The
preferred confirmatory method is gas chromatography/mass spectrometry (GC/MS).
Moreover, clinical considerations and professional judgment should be applied to any
drug-of-abuse test result, particularly when preliminary positive results are used.
Acetaminophen may interfere with home blood glucose measurement systems;
decreases of >20% in mean glucose values may be noted. This effect appears to be
drug, concentration and system dependent.
Use in specific populations
Pregnancy Category C: Animal reproductive studies have not been conducted with oxycodone and acetaminophen tablets. It is also not known whether oxycodone and acetaminophen
tablets can cause fetal harm when administered to a pregnant woman or can affect
reproductive capacity. Oxycodone and acetaminophen tablets should not be given to a
pregnant woman unless in the judgment of the physician, the potential benefits outweigh
the possible hazards.
Fetal/Neonatal Adverse Reactions: Prolonged use of opioid analgesics during pregnancy for medical or non-medical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.
Labor or Delivery: Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist, such as naloxone, must be
available for reversal of opioid-induced respiratory depression in the neonate.
Oxycodone and acetaminophen tablets are not recommended for use in pregnant
women during or immediately prior to labor, when other analgesic techniques are more
Opioid analgesics, including oxycodone and acetaminophen tablets, 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 dilation, which tends to shorten labor. Monitor
neonates exposed to opioid analgesics during labor for signs of excess sedation and
Nursing Mothers: Ordinarily, nursing should not be undertaken while a patient is receiving oxycodone and acetaminophen tablets because of the possibility of sedation and/or respiratory
depression in the infant. Oxycodone is excreted in breast milk in low concentrations,
and there have been rare reports of somnolence and lethargy in babies of nursing
mothers taking an oxycodone/acetaminophen product. Acetaminophen is also excreted
in breast milk in low concentrations.
The developmental and health benefits of breastfeeding should be considered along with
the mother’s clinical need for oxycodone and acetaminophen tablets and any potential
adverse effects on the breastfed infant from oxycodone and acetaminophen tablets or
from the underlying maternal condition.
Pediatric Use: Safety and effectiveness of oxycodone and acetaminophen tablets in pediatric patientshave not been established.
Geriatric Use: Elderly patients (aged 65 years or older) may have increased sensitivity to oxycodone and acetaminophen tablets. In general, use caution when selecting a dosage 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 and of concomitant disease
or other drug therapy.
Respiratory depression is the chief risk for elderly patients treated with opioids, and has
occurred after large initial doses were administered to patients who were not opioid-
tolerant or when opioids were co-administered with other agents that depress
respiration. Titrate the dosage of oxycodone and acetaminophen tablets slowly in
geriatric patients and monitor closely for signs of central nervous system and
Hepatic Impairment: In a pharmacokinetic study of oxycodone in patients with end-stage liver disease, oxycodone plasma clearance decreased and the elimination half-life increased.
Because oxycodone is extensively metabolized in the liver, its clearance may decrease in
patients with hepatic impairment. Initiate therapy in these patients with a lower than
usual dosage of oxycodone and acetaminophen tablets and titrate carefully. Monitor
closely for adverse events such as respiratory depression, sedation, and hypotension
Renal Impairment: In a study of patients with end stage renal impairment, mean elimination half-life was prolonged in uremic patients due to increased volume of distribution and reduced
clearance. Oxycodone should be used with caution in patients with renal impairment.
Because oxycodone is known to be substantially excreted by the kidney, its clearance
may decrease in patients with renal impairment. Initiate therapy with a lower than usual
dosage of oxycodone and acetaminophen tablets and titrate carefully. Monitor closely
for adverse events such as respiratory depression, sedation, and hypotension
The following adverse reactions have been identified during post approval use of
oxycodone and acetaminophen tablets. Because these reactions are reported voluntarily
from a population of uncertain size, it is not always possible to reliably estimate their
frequency or establish a causal relationship to drug exposure.
Serious adverse reactions that may be associated with oxycodone and acetaminophen
use include respiratory depression, apnea, respiratory arrest, circulatory depression,
hypotension, and shock .
The most frequently observed non-serious adverse reactions include lightheadedness,
dizziness, drowsiness or sedation, nausea, and vomiting. These effects seem to be
more prominent in ambulatory than in nonambulatory patients, and some of these
adverse reactions may be alleviated if the patient lies down. Other adverse reactions
include euphoria, dysphoria, constipation, and pruritus.
Hypersensitivity reactions may include: Skin eruptions, urticarial, erythematous skin
reactions. Hematologic reactions may include: thrombocytopenia, neutropenia,
pancytopenia, hemolytic anemia. Rare cases of agranulocytosis have likewise been
associated with acetaminophen use. In high doses, the most serious adverse effect is a
dose-dependent, potentially fatal hepatic necrosis. Renal tubular necrosis and
hypoglycemic coma also may occur.
DRUG ABUSE AND DEPENDENCE
Controlled Substance: Oxycodone and acetaminophen tablets contain oxycodone, a Schedule II controlled substance.
Abuse: Oxycodone and acetaminophen tablets contain oxycodone, a substance with a high
potential for abuse similar to other opioids including fentanyl, hydrocodone,
hydromorphone, methadone, morphine, oxymorphone, and tapentadol. Oxycodone and
acetaminophen tablets can be abused and are subject to misuse, addiction, and criminal
All patients treated with opioids require careful monitoring for signs of abuse and
addiction, since use of opioid analgesic products carries the risk of addiction even underappropriate medical use.
Following an acute overdosage, toxicity may result from the oxycodone or the
Clinical Presentation: Acute overdosage with oxycodone can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia,
hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked
mydriasis rather than miosis may be seen with hypoxia in overdose situations.
Dose-dependent potentially fatal hepatic necrosis is the most serious adverse effect of
acetaminophen overdosage. Renal tubular necrosis, hypoglycemic coma, and
coagulation defects may also occur.
Early symptoms following a potentially hepatotoxic overdose may include: nausea,
vomiting, diaphoresis, and general malaise. Clinical and laboratory evidence of hepatic
toxicity may not be apparent until 48 to 72 hours post-ingestion.
Treatment of Overdose
Oxycodone: In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive
measures (including oxygen and vasopressors) in the management of circulatory shock
and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced
Opioid antagonists, such as naloxone, are specific antidotes to respiratory depression
resulting from opioid overdose. For clinically significant respiratory or circulatory
depression secondary to oxycodone overdose, administer an opioid antagonist.
Acetaminophen: Gastric decontamination with activated charcoal should be administered just prior to N-acetylcysteine (NAC) to decrease systemic absorption if acetaminophen ingestion is
known or suspected to have occurred within a few hours of presentation.
Serum acetaminophen levels should be obtained immediately if the patient presents 4 hours or more after ingestion to assess potential risk of hepatotoxicity; acetaminophen levels
drawn less than 4 hours post-ingestion may be misleading. To obtain the best possible
outcome, NAC should be administered as soon as possible where impending or evolving
liver injury is suspected. Intravenous NAC may be administered when circumstances
preclude oral administration.
Vigorous supportive therapy is required in severe intoxication. Procedures to limit the
continuing absorption of the drug must be readily performed since the hepatic injury is
dose dependent and occurs early in the course of intoxication.
DOSAGE AND ADMINISTRATION
Use the lowest effective dosage for the shortest duration consistent with individual
patient treatment goals.
Initiate the dosing regimen for each patient individually, taking into account the patient’s
severity of pain, patient response, prior analgesic treatment experience, and risk factors
for addiction, abuse, and misuse
Monitor patients closely for respiratory depression, especially within the first 24 to 72
hours of initiating therapy and following dosage increases with oxycodone and
acetaminophen tablets and adjust the dosage accordingly
Initiating Treatment with Oxycodone and Acetaminophen Tablets The usual adult dosage is one tablet every 6 hours as needed for pain. The total daily dose of acetaminophen should not exceed 4 grams.
|Strength||Usual Adult Dosage||Maximal Daily Dose|
|Oxycodone and Acetaminophen Tablets 5 mg/325 mg||1 tablet every 6 hours as needed for pain||12 Tablets|
|Oxycodone and Acetaminophen Tablets 7.5 mg/325 mg||1 tablet every 6 hours as needed for pain||8 Tablets|
|Oxycodone and Acetaminophen Tablets 10 mg/325 mg||1 tablet every 6 hours as needed for pain||6 Tablets|