Endocet (oxycodone HCl/acetaminophen)

It isessential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

To minimize risk of overdosage, recommended age-appropriate daily dosages of acetaminophen should not be exceeded.

Dosage of oxycodone hydrochloride is expressed in terms of the salt; dosage of oxycodone myristate is expressed in terms of oxycodone base.

Oxycodone should be given at the lowest effective dosage and for the shortest duration of therapy consistent with the treatment goals of the patient. Reduced dosage is indicated in debilitated patients and in very young or very old patients. If concomitant therapy with other CNS depressants is required, the lowest effective dosages and shortest possible duration of concomitant therapy should be used. Some manufacturers recommend that initial dosages of 33-50% of the usual dosage be employed when therapy with oxycodone hydrochloride extended-release tablets is initiated in patients receiving other CNS depressants. When therapy with extended-release tablets containing oxycodone hydrochloride in fixed combination with acetaminophen is initiated in patients receiving other CNS depressants, the manufacturer states that the initial oxycodone hydrochloride dosage should be reduced by 50% (i.e., to 7.5 mg twice daily).

For acute pain not related to trauma or surgery, the prescribed quantity should be limited to the amount needed for the expected duration of pain severe enough to require opiate analgesia (generally 3 days or less and rarely more than 7 days). When opiate analgesics are used for the management of chronic noncancer pain, the US Centers for Disease Control and Prevention (CDC) recommends that primary care clinicians carefully reassess individual benefits and risks before prescribing dosages equivalent to 50 mg or more of morphine sulfate daily (approximately 33 mg or more of oxycodone hydrochloride daily) and avoid dosages equivalent to 90 mg or more of morphine sulfate daily (approximately 60 mg or more of oxycodone hydrochloride daily) or carefully justify their decision to titrate the dosage to such levels. Other experts recommend consulting a pain management specialist before exceeding a dosage equivalent to 80-120 mg of morphine sulfate daily.

Patients receiving long-term, daily, around-the-clock opiate analgesia should be reevaluated continually for adequacy of pain control and for adverse effects, as well as for manifestations of opiate withdrawal and for the development of addiction, abuse, or misuse. To reduce the risk of respiratory depression, appropriate dosage selection and titration are essential. The initial dosage of oxycodone must be individualized, taking into account the patient's severity of pain, response, prior analgesic use, and risk factors for addiction, abuse, and misuse. Because there is substantial interpatient variability in the relative potency of opiate analgesics and analgesic formulations, it is preferable to underestimate the patient's 24-hour opiate requirements and provide ''rescue'' therapy with an immediate-release opiate analgesic than to overestimate the requirements and manage an adverse reaction. Patients should be monitored closely for respiratory depression, especially during the first 24-72 hours of therapy and following any increase in dosage.

In patients requiring long-term around-the-clock opiate analgesia, dosage of oxycodone should be titrated to a level that provides adequate analgesia and minimizes adverse effects. Frequent communication among the prescriber, other members of the healthcare team, the patient, and the patient's caregiver or family is important during periods of changing analgesic requirements, including the initial dosage titration period. Patients who experience breakthrough pain may require dosage adjustment or supplemental analgesia (i.e., ''rescue'' therapy with an immediate-release analgesic). If the level of pain increases after dosage stabilization, an attempt should be made to identify the source of increased pain before increasing the oxycodone dosage. During long-term therapy, the continued need for opiate analgesics should be continually reevaluated. If discontinuance of opiate therapy is required, the dosage should be tapered gradually to avoid manifestations of abrupt withdrawal.

For further information on the management of opiate analgesic therapy, see Dosage and Administration: Dosage, in the Opiate Agonists General Statement 28:08.08.

Oxycodone/acetaminophen should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks.

Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals.

Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available.

Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse.

Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with oxycodone/acetaminophen. Consider this risk when selecting an initial dose and when making dose adjustments.

Discuss opioid overdose reversal agents and options for acquiring them with the patient and/or caregiver, both when initiating and renewing treatment with oxycodone/acetaminophen, especially if the patient has additional risk factors for overdose, or close contacts at risk for exposure and overdose.

Dosage of oxycodone/acetaminophen tablets: Initiate treatment using oxycodone hydrochloride and acetaminophen 2.5 mg/325 mg tablets in a dosing range of 1 to 2 tablets every 6 hours as needed for pain, at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient's response to their initial dose. The total daily dose of acetaminophen should not exceed 4 grams. When using the fixed combination of 2.5 mg/325 mg, the usual adult dosage is 1 or 2 tablets every 6 hours as needed for pain (maximum daily dose of 12 tablets). When using the fixed combination of 5 mg/325 mg, the usual adult dosage is 1 tablet every 6 hours as needed for pain (maximum daily dose of 12 tablets). When using the fixed combination of 7.5 mg/325 mg, the usual adult dosage is 1 tablet every 6 hours as needed for pain (maximum daily dose of 8 tablets). When using the fixed combination of 10 mg/325 mg, the usual adult dosage is 1 tablet every 6 hours as needed for pain (maximum daily dose of 6 tablets).

Dosage of oxycodone/acetaminophen oral solution: Initiate treatment with oxycodone hydrochloride and acetaminophen oral solution at a dose of 5 mL (one teaspoonful) every 6 hours as needed for pain, at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient's response to their initial dose. The total daily dose of acetaminophen should not exceed 4 grams. Maximum daily dose is 12 teaspoonfuls or 60 mL.

Conversion from oxycodone/acetaminophen to extended-release oxycodone: The relative bioavailability of oxycodone/acetaminophen tablets or oral solution compared to extended-release oxycodone is unknown, so conversion to extended-release oxycodone may lead to an increased risk of excessive sedation and respiratory depression.

Adjust the dosage of oxycodone/acetaminophen to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

Do not rapidly reduce or abruptly discontinue oxycodone/acetaminophen in patients who may be physically dependent on opioids. Rapid reduction or abrupt discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide.

In patients with impaired hepatic function, initial oxycodone dosages should be conservative and adjusted according to the clinical situation. The manufacturers recommend that therapy with oxycodone hydrochloride extended-release tablets or oxycodone myristate extended-release capsules be initiated at 33-50% of the usual dosage and titrated carefully. When extended-release tablets containing oxycodone hydrochloride in fixed combination with acetaminophen are used for the management of acute pain in patients with hepatic impairment, the manufacturer recommends an initial oxycodone hydrochloride dose of 7.5 mg (given in fixed combination with 325 mg of acetaminophen); dosage should be adjusted as needed with close monitoring for respiratory depression.

In patients with impaired renal function (creatinine clearance less than 60 mL/minute), initial oxycodone dosages should be conservative and adjusted according to the clinical situation. When extended-release tablets containing oxycodone hydrochloride in fixed combination with acetaminophen are used for the management of acute pain in patients with renal impairment, the manufacturer recommends an initial oxycodone hydrochloride dose of 7.5 mg (given in fixed combination with 325 mg of acetaminophen); dosage should be adjusted as needed with close monitoring for respiratory depression.

If the required dose of oxycodone myristate extended-release capsules is less than 9 mg of oxycodone, an alternative analgesic should be selected.

Acetaminophen injection is administered by IV infusion over 15 minutes.

Acetaminophen is also commercially available in fixed-combination with ibuprofen (Combogesic(R)IV) for IV administration. See the full prescribing information for administration of this combination product.

Several commercially available fixed-combination prescription preparations containing acetaminophen are also available for oral use. See the full prescribing information for administration of these combination products.

Acetaminophen is commercially available in various oral and rectal over-the-counter (OTC) preparations as a single ingredient or in combination with other analgesics (e.g., ibuprofen), antihistamines, or decongestants. See the FDA Orange Book and the manufacturer's Drug Facts for further information.

Oxycodone is administered orally as the hydrochloride salt, often in combination with nonopiate analgesics (e.g., acetaminophen), or as the myristate salt.

No dosing information is available for this tab.

No dosing information is available for this tab.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Significant respiratory depression.

*Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment.

*Known or suspected GI obstruction, including paralytic ileus.

*Hypersensitivity to oxycodone, acetaminophen, or any other component of the product (e.g., anaphylaxis).

*Known hypersensitivity to acetaminophen or any ingredient in the formulation.

*Severe hepatic impairment or severe active liver disease.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

The most common adverse effects reported in clinical trials in >=5% of patients receiving IV acetaminophen were nausea, vomiting, headache, and insomnia in adults and nausea, vomiting, constipation, and pruritus in pediatric patients.

Common adverse effects associated with oral or rectal administration of acetaminophen include skin rash, hypersensitivity reactions, nephrotoxicity, and hematologic abnormalities (e.g., anemia, leukopenia, neutropenia, and pancytopenia).

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

The safety and effectiveness of oxycodone/acetaminophen in pediatric patients have not been established.

Use of IV acetaminophen for analgesia in pediatric patients >=2 years of age is supported by evidence from adequate and well-controlled studies of IV acetaminophen in adults and additional safety and pharmacokinetic data from 483 pediatric patients ranging in age from neonates to adolescents. Efficacy of IV acetaminophen for analgesia has not been established in pediatric patients <2 years of age.

Use of IV acetaminophen for fever in pediatric patients <2 years of age, including premature neonates (postmenstrual age of at least 32 weeks) is supported by evidence from adequate and well-controlled studies of IV acetaminophen in adults, clinical data in pediatric patients >=2 years of age, and additional safety and pharmacokinetic data from 239 patients <2 years of age, including neonates with a postmenstrual age of at least 32 weeks.

Animal reproductive studies have not been conducted with oxycodone/acetaminophen. It is also not known whether oxycodone/acetaminophen can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Oxycodone/acetaminophen should not be given to a pregnant woman unless in the judgment of the physician, the potential benefits outweigh the possible hazards.

Use of opioid analgesics for an extended period of time during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.

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. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly.

Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid overdose reversal agent, such as naloxone or nalmefene, must be available for reversal of opioid-induced respiratory depression in the neonate. Oxycodone/acetaminophen is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including oxycodone/acetaminophen, 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.

Epidemiologic data regarding oral acetaminophen use in pregnant females have shown no increased risk of major congenital malformations in infants exposed in utero to the medication. In a large population-based prospective cohort study involving more than 26,000 females with live-born singleton infants who were exposed to oral acetaminophen during the first trimester of pregnancy, no increase in the risk of congenital malformations was observed in exposed children compared with a control group of unexposed children; rate of congenital malformations (4.3%) was similar to the rate in the general population. A population-based, case-control study from the National Birth Defects Prevention Study also found no increase in the risk of major birth defects in a group of 11,610 children who had been exposed to acetaminophen during the first trimester of pregnancy compared with a control group of 4,500 children.

Animal reproduction studies in pregnant rats given oral acetaminophen during organogenesis at dosages up to 0.85 times the maximum recommended human daily dosage (4 g daily, based on body surface area comparison) showed evidence of fetotoxicity (reduced fetal weight and length) and a dose-related increase in bone variations (reduced ossification and rudimentary rib changes); the offspring showed no evidence of external, visceral, or skeletal malformations. When pregnant rats received oral acetaminophen throughout gestation at a dosage of 1.2 times the maximum recommended human daily dosage, areas of necrosis occurred in both the liver and kidney of pregnant rats and fetuses; these effects did not occur in animals given acetaminophen at dosages of 0.3 times the maximum recommended human dosage.

In a continuous breeding study in which pregnant mice were given acetaminophen at dosages approximately equivalent to 0.43, 0.87, or 1.7 times the maximum recommended human daily dosage (based on body surface area comparison), a dose-related reduction in body weight of the fourth and fifth litter offspring of the treated mating pair occurred during lactation and following weaning at all dosages studied. Animals receiving the highest dosage had a reduced number of litters per mating pair, male offspring with an increased percentage of abnormal sperm, and reduced birth weights in the next-generation pups.

The manufacturer states that there are no animal reproductive studies with IV acetaminophen.

A correlation between acetaminophen use during pregnancy and neurodevelopmental disorders in children, including autism and attention-deficit/hyperactivity disorder (ADHD), has been observed in studies; however, inconsistent findings have been reported in the literature and a causal relationship has not been established. Results of 2 high-quality studies with sibling controls indicate prenatal exposure to acetaminophen was not associated with an increased risk of a neurodevelopmental diagnosis. There are unmeasured familial confounding factors that may explain the apparent association observed in some studies. Acetaminophen is considered the preferred analgesic/antipyretic for use during pregnancy because of its relatively favorable safety profile compared with other common analgesics. The American College of Obstetricians and Gynecologists (ACOG) supports use of acetaminophen during pregnancy when taken as needed in moderation and after consultation with a doctor. There is no evidence to support any risk associated with appropriate use of acetaminophen during pregnancy. However, untreated maternal fever and pain pose risks such as neural tube defects and preterm birth, necessitating a balanced approach.

Available data from lactation studies indicate that oxycodone is present in breastmilk and that doses of less than 60 mg/day of the immediate-release formulation are unlikely to result in clinically relevant exposures in breastfed infants. A pharmacokinetics study utilizing opportunistic sampling of 76 lactating women receiving oxycodone immediate-release products for postpartum pain management showed that oxycodone concentrates in breastmilk with an average milk to plasma ratio of 3.2. The relative infant dose was low, approximately 1.3% of a weight-adjusted maternal dose. In the same study, among the 70 infants exposed to oxycodone in breastmilk, no adverse events were attributed to oxycodone. However, based on known adverse effects in adults, infants should be monitored for signs of excess sedation and respiratory depression. There are no data on the effects of the oxycodone on milk production.

Acetaminophen is 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/acetaminophen and any potential adverse effects on the breastfed infant from the drugs or from the underlying maternal condition.

Infants exposed to oxycodone/acetaminophen through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breastfeeding is stopped.

It is not known if IV acetaminophen is excreted into human milk; however, data suggest following oral administration of acetaminophen, infant exposure is approximately 1-2% of the weight-adjusted maternal daily dosage. Limited published studies report acetaminophen passes rapidly into human milk with similar levels noted in milk and plasma. A case of rash in a breast-fed infant has been reported; the rash resolved when the mother discontinued acetaminophen use and recurred when she resumed acetaminophen therapy. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for acetaminophen and any potential adverse effects on the breast-fed infant from exposure to the medication or to the underlying maternal condition.

The manufacturer makes no specific dosage recommendations for geriatric patients. Although no overall differences in efficacy or safety were observed between geriatric and younger patients, and other clinical experience revealed no evidence of age-related differences, the possibility that some older patients may exhibit increased sensitivity to IV acetaminophen cannot be ruled out.

Elderly patients (65 years of age or older) may have increased sensitivity to oxycodone/acetaminophen. 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/acetaminophen slowly in geriatric patients and frequently reevaluate the patient for signs of CNS depression.

These drugs are known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function.

When the total number of patients studied in clinical trials of IV acetaminophen is considered, 15% were >=65 years of age, while 5% were >=75 years of age. Although no overall differences in efficacy or safety were observed between geriatric and younger patients, and other clinical experience revealed no evidence of age-related differences, the possibility some older patients may exhibit increased sensitivity to acetaminophen cannot be ruled out.