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Hotoprete.bizOxycodone hydrochloride
6/22/2016
05:21 | Olivia Holiday
Oxycodone hydrochloride
DailyMed

As with all opioids, the dose must be individualized (see DOSAGE AND ADMINISTRATION ), because the effective analgesic dose for some patients will be too high to be tolerated by other patients.

Dose proportionality has been established for the 10 mg, 20 mg, 40 mg, and 80 mg tablet strengths for both peak plasma concentrations (C max ) and extent of absorption (AUC) (see Table 1 below). Another study established that the 160 mg tablet is bioequivalent to 2 x 80 mg tablets as well as to 4 x 40 mg for both peak plasma concentrations (C max ) and extent of absorption (AUC) (see Table 2 below). Given the short half-life of elimination of oxycodone from Oxycodone HCl Controlled-Release Tablets, steady-state plasma concentrations of oxycodone are achieved within 24-36 hours of initiation of dosing with Oxycodone HCl Controlled-Release Tablets. In a study comparing 10 mg of Oxycodone HCl Controlled-Release Tablets every 12 hours to 5 mg of immediate-release oxycodone every 6 hours, the two treatments were found to be equivalent for AUC and C max, and similar for C min (trough) concentrations.

Oxycodone HCl Controlled-Release Tablets are a controlled-release oral formulation of oxycodone hydrochloride indicated for the management of moderate to severe pain when a continuous, around-the-clock analgesic is needed for an extended period of time.

Food has no significant effect on the extent of absorption of oxycodone from Oxycodone HCl Controlled-Release Tablets. However, the peak plasma concentration of oxycodone increased by 25% when an Oxycodone HCl Controlled-Release Tablets 160 mg Tablet was administered with a high-fat meal.

Oxycodone can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing Oxycodone HCl Controlled-Release Tablets in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.

Data from a study involving 24 patients with mild to moderate hepatic dysfunction show peak plasma oxycodone and noroxycodone concentrations 50% and 20% higher, respectively, than normal subjects. AUC values are 95% and 65% higher, respectively. Oxymorphone peak plasma concentrations and AUC values are lower by 30% and 40%. These differences are accompanied by increases in some, but not other, drug effects. The t½ elimination for oxycodone increased by 2.3 hours (see PRECAUTIONS ).

Oxycodone depresses the cough reflex by direct effect on the cough center in the medulla. Antitussive effects may occur with doses lower than those usually required for analgesia.

PATIENTS SHOULD BE INSTRUCTED AGAINST USE BY INDIVIDUALS OTHER THAN THE PATIENT FOR WHOM IT WAS PRESCRIBED, AS SUCH INAPPROPRIATE USE MAY HAVE SEVERE MEDICAL CONSEQUENCES, INCLUDING DEATH.

Oxycodone HCl Controlled-Release Tablets are NOT INDICATED FOR RECTAL ADMINISTRATION. Data from a study involving 21 normal volunteers show that Oxycodone HCl Controlled-Release Tablets administered per rectum resulted in an AUC 39% greater and a Cmax 9% higher than tablets administered by mouth. Therefore, there is an increased risk of adverse events with rectal administration.

Oxycodone HCl Controlled-Release Tablets are associated with typical opioid-related adverse experiences. There is a general relationship between increasing oxycodone plasma concentration and increasing frequency of dose-related opioid adverse experiences such as nausea, vomiting, CNS effects, and respiratory depression. In opioid-tolerant patients, the situation is altered by the development of tolerance to opioid-related side effects, and the relationship is not clinically relevant.

Oxycodone is a pure agonist opioid whose principal therapeutic action is analgesia. Other members of the class known as opioid agonists include substances such as morphine, hydromorphone, fentanyl, codeine, and hydrocodone. Pharmacological effects of opioid agonists include anxiolysis, euphoria, feelings of relaxation, respiratory depression, constipation, miosis, and cough suppression, as well as analgesia. Like all pure opioid agonist analgesics, with increasing doses there is increasing analgesia, unlike with mixed agonist/antagonists or non-opioid analgesics, where there is a limit to the analgesic effect with increasing doses. With pure opioid agonist analgesics, there is no defined maximum dose; the ceiling to analgesic effectiveness is imposed only by side effects, the more serious of which may include somnolence and respiratory depression.

The activity of Oxycodone HCl Controlled-Release Tablets is primarily due to the parent drug oxycodone. Oxycodone HCl Controlled-Release Tablets are designed to provide controlled delivery of oxycodone over 12 hours.

Following intravenous administration, the volume of distribution (Vss) for oxycodone was 2.6 L/kg. Oxycodone binding to plasma protein at 37°C and a pH of 7.4 was about 45%. Once absorbed, oxycodone is distributed to skeletal muscle, liver, intestinal tract, lungs, spleen, and brain. Oxycodone has been found in breast milk (see PRECAUTIONS ).

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Oxycodone and its metabolites are excreted primarily via the kidney. The amounts measured in the urine have been reported as follows: free oxycodone up to 19%; conjugated oxycodone up to 50%; free oxymorphone 0%; conjugated oxymorphone ≤ 14%; both free and conjugated noroxycodone have been found in the urine but not quantified. The total plasma clearance was 0.8 L/min for adults. Elderly.

Oxycodone is an opioid agonist of the morphine-type. Such drugs are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.

As with all opioids, the minimum effective plasma concentration for analgesia will vary widely among patients, especially among patients who have been previously treated with potent agonist opioids. As a result, patients must be treated with individualized titration of dosage to the desired effect. The minimum effective analgesic concentration of oxycodone for any individual patient may increase over time due to an increase in pain, the development of a new pain syndrome and/or the development of analgesic tolerance.

Oxycodone causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origin may produce similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in the setting of Oxycodone HCl Controlled-Release Tablets overdose (See OVERDOSAGE ).

The plasma concentrations of oxycodone are only nominally affected by age, being 15% greater in elderly as compared to young subjects. Gender.

Oxycodone HCl Controlled-Release Tablets are NOT intended for use as a prn analgesic.

Data from a pharmacokinetic study involving 13 patients with mild to severe renal dysfunction (creatinine clearance <60 mL/min) show peak plasma oxycodone and noroxycodone concentrations 50% and 20% higher, respectively, and AUC values for oxycodone, noroxycodone, and oxymorphone 60%, 50%, and 40% higher than normal subjects, respectively. This is accompanied by an increase in sedation but not by differences in respiratory rate, pupillary constriction, or several other measures of drug effect. There was an increase in t½ of elimination for oxycodone of only 1 hour (see PRECAUTIONS ). Hepatic Impairment.

Oxycodone HCl Controlled-Release Tablets are a controlled-release oral formulation of oxycodone hydrochloride indicated for the management of moderate to severe pain when a continuous, around-the-clock analgesic is needed for an extended period of time.

Oxycodone HCl Controlled-Release Tablets are NOT intended for use as a prn analgesic.

The chemical formula is 4, 5α-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one hydrochloride.

Oxycodone HCl Controlled-Release Tablets are not indicated for pain in the immediate postoperative period (the first 12-24 hours following surgery), or if the pain is mild, or not expected to persist for an extended period of time. Oxycodone HCl Controlled-Release Tablets are only indicated for postoperative use if the patient is already receiving the drug prior to surgery or if the postoperative pain is expected to be moderate to severe and persist for an extended period of time. Physicians should individualize treatment, moving from parenteral to oral analgesics as appropriate. (See American Pain Society guidelines.).

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 play a role in the analgesic effects of this drug.

C 18 H 21 NO 4 • HCl MW 351.83.

Oxycodone HCl Controlled-Release Tablets are an opioid agonist and a Schedule II controlled substance with an abuse liability similar to morphine.

Oxycodone HCL controlled-release 10 mg and 20 mg tablets are tested using USP dissolution test 2 and meet the associated tolerances provided in acceptance table 2 of the oxycodone hydrochloride extended-release tablets USP monograph.

Oxycodone causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm resulting in constipation. Other opioid-induced effects may include a reduction in gastric, biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase.

Concerns about abuse, addiction, and diversion should not prevent the proper management of pain.

Oxycodone can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing Oxycodone HCl Controlled-Release Tablets in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.

Updated January 14, 2010.

Oxycodone HCl Controlled-Release Tablets are an opioid analgesic supplied in 10 mg and 20 mg tablet strengths for oral administration. The tablet strengths describe the amount of oxycodone per tablet as the hydrochloride salt. The structural formula for oxycodone hydrochloride is as follows:

CYP3A mediated N-demethylation (to noroxycodone) is the primary metabolic pathway of oxycodone with a lower contribution from CYP2D6 mediated O-demethylation (to oxymorphone). Therefore, the formation of these and related metabolites can, in theory, be affected by other drugs (see Drug-Drug Interactions ).

OXYCODONE HCl CONTROLLED-RELEASE TABLETS ARE TO BE SWALLOWED WHOLE AND ARE NOT TO BE BROKEN, CHEWED, OR CRUSHED. TAKING BROKEN, CHEWED, OR CRUSHED OXYCODONE HCl CONTROLLED-RELEASE TABLETS LEADS TO RAPID RELEASE AND ABSORPTION OF A POTENTIALLY FATAL DOSE OF OXYCODONE.

The 20 mg tablets also contain: polysorbate 80 and red iron oxide.

Physicians should individualize treatment in every case, initiating therapy at the appropriate point along a progression from non-opioid analgesics, such as non-steroidal anti-inflammatory drugs and acetaminophen to opioids in a plan of pain management such as outlined by the World Health Organization, the Agency for Healthcare Research and Quality (formerly known as the Agency for Health Care Policy and Research), the Federation of State Medical Boards Model Guidelines, or the American Pain Society.

Oxycodone release from Oxycodone HCl Controlled-Release Tablets is pH independent. Oxycodone is well absorbed from Oxycodone HCl Controlled-Release Tablets with an oral bioavailability of 60% to 87%. The relative oral bioavailability of Oxycodone HCl Controlled-Release Tablets to immediate-release oral dosage forms is 100%. Upon repeated dosing in normal volunteers in pharmacokinetic studies, steady-state levels were achieved within 24-36 hours. Dose proportionality and/or bioavailability has been established for the 10 mg, 20 mg, 40 mg, 80 mg, and 160 mg tablet strengths for both peak plasma levels (Cmax) and extent of absorption (AUC). Oxycodone is extensively metabolized and eliminated primarily in the urine as both conjugated and unconjugated metabolites. The apparent elimination half-life of oxycodone following the administration of Oxycodone HCl Controlled-Release Tablets was 4.5 hours compared to 3.2 hours for immediate-release oxycodone.

Oxycodone may produce release of histamine with or without associated peripheral vasodilation. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension.

The 10 mg tablets also contain: hydroxypropyl cellulose.

Oxycodone is metabolized in part by cytochrome P450 2D6 to oxymorphone which represents less than 15% of the total administered dose. This route of elimination may be blocked by a variety of drugs (e.g., certain cardiovascular drugs including amiodarone and quinidine as well as polycyclic anti-depressants). However, in a study involving 10 subjects using quinidine, a known inhibitor of cytochrome P450 2D6, the pharmacodynamic effects of oxycodone were unchanged.

Oxycodone HCl Controlled-Release 80 mg Tablets, or a single dose greater than 40 mg, ARE FOR USE IN OPIOID-TOLERANT PATIENTS ONLY. A single dose greater than 40 mg, or total daily doses greater than 80 mg, may cause fatal respiratory depression when administered to patients who are not tolerant to the respiratory depressant effects of opioids.

Oxycodone may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression.

OXYCODONE HCl CONTROLLED-RELEASE TABLETS ARE TO BE SWALLOWED WHOLE AND ARE NOT TO BE BROKEN, CHEWED, OR CRUSHED. TAKING BROKEN, CHEWED, OR CRUSHED OXYCODONE HCl CONTROLLED-RELEASE TABLETS LEADS TO RAPID RELEASE AND ABSORPTION OF A POTENTIALLY FATAL DOSE OF OXYCODONE.

Oxycodone hydrochloride is extensively metabolized to noroxycodone, oxymorphone, noroxymorphone, and their glucuronides. The major circulating metabolite is noroxycodone. Noroxycodone is reported to be a considerably weaker analgesic than oxycodone. Oxymorphone, although possessing analgesic activity, is present in the plasma only in low concentrations. The correlation between oxymorphone concentrations and opioid effects was much less than that seen with oxycodone plasma concentrations. The analgesic activity profile of other metabolites is not known.

Studies in normal volunteers and patients reveal predictable relationships between oxycodone dosage and plasma oxycodone concentrations, as well as between concentration and certain expected opioid effects, such as pupillary constriction, sedation, overall “drug effect”, analgesia and feelings of “relaxation”

CYP3A mediated N-demethylation is the principal metabolic pathway of oxycodone with a lower contribution from CYP2D6 mediated O-demethylation and in theory can be affected by drugs affecting cytochrome P450 enzymes.

Oxycodone HCl Controlled-Release Tablets contain Oxycodone which is a full mu-agonist opiod with an abuse liability similar to morphine and is a schedule II controlled substance. Oxycodone, like morphine and other opiods used in analgesia, can be abused and is subject to criminal diversion.

About 60% to 87% of an oral dose of oxycodone reaches the central compartment in comparison to a parenteral dose. This high oral bioavailability is due to low pre-systemic and/or first-pass metabolism. In normal volunteers, the t ½ of absorption is 0.4 hours for immediate-release oral oxycodone. In contrast, Oxycodone HCl Controlled-Release Tablets exhibit a biphasic absorption pattern with two apparent absorption half-lives of 0.6 and 6.9 hours, which describes the initial release of oxycodone from the tablet followed by a prolonged release.

A single-dose, double-blind, placebo- and dose-controlled study was conducted using Oxycodone HCl Controlled-Release Tablets (10, 20, and 30 mg) in an analgesic pain model involving 182 patients with moderate to severe pain. Twenty and 30 mg of Oxycodone HCl Controlled-Release Tablets were superior in reducing pain compared with placebo, and this difference was statistically significant. The onset of analgesic action with Oxycodone HCl Controlled-Release Tablets occurred within 1 hour in most patients following oral administration.

Healthcare professionals should contact their State Professional Licensing Board, or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.

OXYCODONE HCl CONTROLLED-RELEASE 80 mg, and 160 mg Tablets, or a single dose greater than 40 mg, ARE FOR USE IN OPIOID-TOLERANT PATIENTS ONLY. A single dose greater than 40 mg, or total daily doses greater than 80 mg, may cause fatal respiratory depression when administered to patients who are not tolerant to the respiratory depressant effects of opioids.

Oxycodone HCl Controlled-Release Tablets are contraindicated in patients with known hypersensitivity to oxycodone, or in any situation where opioids are contraindicated. This includes patients with significant respiratory depression (in unmonitored settings or the absence of resuscitative equipment), and patients with acute or severe bronchial asthma or hypercarbia. Oxycodone HCl Controlled-Release Tablets are contraindicated in any patient who has or is suspected of having paralytic ileus.

Oxycodone is a white, odorless crystalline powder derived from the opium alkaloid, thebaine. Oxycodone hydrochloride dissolves in water (1 g in 6 to 7 mL). It is slightly soluble in alcohol (octanol water partition coefficient 0.7). The tablets contain the following inactive ingredients: ammonio methacrylate copolymer, hypromellose, lactose, magnesium stearate, polyethylene glycol 400, povidone, sodium hydroxide, sorbic acid, stearyl alcohol, talc, titanium dioxide, and triacetin.

Breaking, chewing or crushing Oxycodone HCl Controlled-Release Tablets eliminates the controlled delivery mechanism and results in the rapid release and absorption of a potentially fatal dose of oxycodone.

Oxycodone produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves both a reduction in the responsiveness of the brain stem respiratory centers to increases in carbon dioxide tension and to electrical stimulation.

A double-blind placebo-controlled, fixed-dose, parallel group, two-week study was conducted in 133 patients with chronic, moderate to severe pain, who were judged as having inadequate pain control with their current therapy. In this study, 20 mg Oxycodone HCl Controlled-Release Tablets q12h but not 10 mg Oxycodone HCl Controlled-Release Tablets q12h decreased pain compared with placebo, and this difference was statistically significant.

Oxycodone HCl Controlled-Release Tablets have been reported as being abused by crushing, chewing, snorting, or injecting the dissolved product. These practices will result in the uncontrolled delivery of the opioid and pose a significant risk to the abuser that could result in overdose and death (see WARNINGS and DRUG ABUSE AND ADDICTION ).

Female subjects have, on average, plasma oxycodone concentrations up to 25% higher than males on a body weight adjusted basis. The reason for this difference is unknown. Renal Impairment.

† for single-dose AUC = AUC 0-inf ; for multiple-dose AUC = AUC 0-T.

* data obtained while volunteers received naltrexone which can enhance absorption.

Oxycodone hydrochloride