OxyContin

OxyContin Information

Generic name: sustained release oxycodone

OxyContin (oxycodone HCl) 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.

OxyContin is NOT intended for use as a prn analgesic.

OxyContin is not indicated for pain in the immediate post-operative 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. OxyContin is only indicated for post-operative 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.

How Does OxyContin Work?

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 (i.e. OxyContin) 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 affect 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.

OxyContin effects on:

The Central Nervous System

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.

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.

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.

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 OxyContin overdose.

Gastrointestinal Tract and Other Smooth Muscle

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.

Cardiovascular System

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.

Concentration-Efficacy Relationships

Studies in normal volunteers and patients reveal predictable relationships between OxyContin (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.

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.

Concentration-Adverse Experience Relationships

OxyContin 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.

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

OxyContin Ingredients and Composition

How To Take OxyContin and OxyContin Dosage and Administration

OxyContin is an opioid agonist and a SCHEDULE II CONTROLLED SUBSTANCE with an abuse liability similar to morphine.

Oxycodone, like morphine and other opioids used in pain suppression, can be abused and is subject to criminal diversion.

OxyContin (oxycodone hydrochloride controlled-release) tablets are to be swallowed whole, and are not to be broken, chewed or crushed. Takin broken, chewed or crushed OxyContin tablets leads to the rapid release and absorption of a potentially FATAL DOSE of Oxycodone.

One OxyContin 160 mg tablet is comparable to two OxyContin 80 mg tablets when taken on an empty stomach. With a high fat meal, however, there is a 25% greater peak plasma concentration following one 160 mg OxyContin tablet. Dietary caution should be taken when patients are initially titrated to 160 mg OxyContin tablets.

In treating pain it is vital to assess the patient regularly and systematically. Therapy should also be regularly reviewed and adjusted based upon the patient's own reports of pain and side effects and the health professional's clinical judgment.

OxyContin tablets are a controlled-release oral formulation of oxycodone hydrochloride indicated for the management of moderate to severe pain requiring treatment with a strong opioid for continuous, around-the-clock analgesia for an extended period of time. The controlled-release nature of the formulation allows OxyContin to be effectively administered every 12 hours. While symmetric (same dose AM and PM), around-the-clock, 12h dosing is appropriate for the majority of patients, some patients may benefit from asymmetric (different OxyContin dose given in AM than in PM) dosing, tailored to their pain pattern. It is usually appropriate to treat a patient with only one opioid for around-the-clock therapy.

Physicians should individualize treatment using a progressive plan of pain management such as outlined by the World Health Organization, the American Pain Society and the Federation of State Medical Boards Model Guidelines. Health care professionals should follow appropriate pain management principles of careful assessment and ongoing monitoring.

Initiation of Therapy

It is critical to initiate the dosing regimen for each patient individually, taking into account the patient's prior opioid and non-opioid analgesic treatment. Attention should be given to:

the general condition and medical status of the patient;

the daily dose, potency, and kind of the analgesic(s) the patient has been taking;
the reliability of the conversion estimate used to calculate the dose of oxycodone;
the patient's opioid exposure and opioid tolerance (if any);
special safety issues associated with conversion to OxyContin doses at or exceeding 160 mg q12h (see Special Instructions for OxyContin 80 mg and 160 mg Tablets); and
the balance between pain control and adverse experiences.

Care should be taken to use low initial doses of OxyContin in patients who are not already opioid-tolerant, especially those who are receiving concurrent treatment with muscle relaxants, sedatives, or other CNS active medications.

For initiation of OxyContin therapy for patients previously taking opioids, the conversion ratios from Foley, KM. [NEJM, 1985; 313:84-95], are a reasonable starting point, although not verified in well-controlled, multiple-dose trials.

Experience indicates a reasonable starting dose of OxyContin for patients who are taking non-opioid analgesics and require continuous around-the-clock therapy for an extended period of time is 10 mg q12h. If a non-opioid analgesic is being provided, it may be continued. OxyContin should be individually titrated to a dose that provides adequate analgesia and minimizes side effects.

Using standard conversion ratio estimates, multiply the mg/day of the previous opioids by the appropriate multiplication factors to obtain the equivalent total daily dose of oral oxycodone.

When converting from oxycodone, divide the 24-hour oxycodone dose in half to obtain the twice a day (q12h) dose of OxyContin.
Round down to a dose which is appropriate for the tablet strengths available (10 mg, 20 mg, 40 mg, 80 mg, and 160 mg tablets).
Discontinue all other around-the-clock opioid drugs when OxyContin therapy is initiated.
No fixed conversion ratio is likely to be satisfactory in all patients, especially patients receiving large opioid doses.

Individualization of Dosage

Once OxyContin therapy is initiated, pain relief and other opioid effects should be frequently assessed. Patients should be titrated to adequate effect (generally mild or no pain with the regular use of no more than two doses of supplemental analgesia per 24 hours). Patients who experience breakthrough pain may require dosage adjustment or rescue medication. Because steady-state plasma concentrations are approximated within 24 to 36 hours, dosage adjustment may be carried out every 1 to 2 days. It is most appropriate to increase the q12h dose, not the dosing frequency. There is no clinical information on OxyContin dosing intervals shorter than q12h. As a guideline, except for the increase from 10 mg to 20 mg q12h, the total daily oxycodone dose usually can be increased by 25% to 50% of the current dose at each increase.

If signs of excessive opioid-related adverse experiences are observed, the next dose may be reduced. If this adjustment leads to inadequate analgesia, a supplemental dose of immediate-release oxycodone may be given. Alternatively, non-opioid analgesic adjuvants may be employed. Dose adjustments should be made to obtain an appropriate balance between pain relief and opioid-related adverse experiences.

If significant OxyContin adverse events occur before the therapeutic goal of mild or no pain is achieved, the events should be treated aggressively. Once adverse events are under control, upward titration should continue to an acceptable level of pain control.

During periods of changing analgesic requirements, including initial titration, frequent contact is recommended between physician, other members of the healthcare team, the patient and the caregiver/family.

Special Instructions for OxyContin 80 mg and 160 mg Tablets (For use in opioid-tolerant patients only)

OxyContin 80 mg and 160 mg Tablets are for use only in opioid-tolerant patients requiring daily oxycodone equivalent dosages of 160 mg or more for the 80 mg tablet and 320 mg or more for the 160 mg tablet. Care should be taken in the prescribing of these OxyContin tablet strengths. 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.

One OxyContin 160 mg tablet is comparable to two 80 mg tablets when taken on an empty stomach. With a high fat meal, however, there is a 25% greater peak plasma concentration following one 160 mg tablet. Dietary caution should be taken when patients are initially titrated to 160 mg tablets.

Supplemental Analgesia

Most patients given around-the-clock therapy with controlled-release opioids may need to have immediate-release medication available for exacerbations of pain or to prevent pain that occurs predictably during certain patient activities (incident pain).

Maintenance of Therapy

The intent of the titration period is to establish a patient-specific q12h dose that will maintain adequate analgesia with acceptable side effects for as long as pain relief is necessary. Should pain recur then the dose can be incrementally increased to re-establish pain control. The method of therapy adjustment outlined above should be employed to re-establish pain control.

During chronic therapy, especially for non-cancer pain syndromes, the continued need for around-the-clock opioid therapy should be reassessed periodically (e.g., every 6 to 12 months) as appropriate.

Cessation of Therapy

When the patient no longer requires therapy with OxyContin tablets, doses should be tapered gradually to prevent signs and symptoms of withdrawal in the physically dependent patient.

If you suspect a OxyContin Overdose

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, bradycardia, hypotension, and death.

Deaths due to overdose have been reported with abuse and misuse of OxyContin, by ingesting, inhaling, or injecting the crushed tablets. Review of case reports has indicated that the risk of fatal overdose is further increased when OxyContin is abused concurrently with alcohol or other CNS depressants, including other opioids.

In the treatment of oxycodone overdosage, primary attention should be given to the re-establishment of a patent airway and institution of assisted or controlled ventilation. Supportive measures (including oxygen and vasopressors) should be employed in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation.

The pure opioid antagonists such as naloxone or nalmefene are specific antidotes against respiratory depression from opioid overdose. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to oxycodone overdose. In patients who are physically dependent on any opioid agonist including OxyContin, an abrupt or complete reversal of opioid effects may precipitate an acute abstinence syndrome. The severity of the withdrawal syndrome produced will depend on the degree of physical dependence and the dose of the antagonist administered. Please see the prescribing information for the specific opioid antagonist for details of their proper use.

OxyContin Side Effects

OxyContin Precautions and Contraindications

OxyContin is 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. OxyContin is contraindicated in any patient who has or is suspected of having paralytic ileus.

Patients should be aware that they should not adjust the dose of OxyContin without consulting the prescribing professional.

Patients should be advised that OxyContin may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating heavy machinery).

Patients should not combine OxyContin with alcohol or other central nervous system depressants (sleep aids, tranquilizers) except by the orders of the prescribing physician, because dangerous additive effects may occur, resulting in serious injury or death.

Respiratory Depression

Respiratory depression is the chief hazard from oxycodone, the active ingredient in OxyContin, as with all opioid agonists. Respiratory depression is a particular problem in elderly or debilitated patients, usually following large initial doses in nontolerant patients, or when opioids are given in conjunction with other agents that depress respiration.

Oxycodone should be used with extreme caution in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and in patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression. In such patients, even usual therapeutic doses of oxycodone may decrease respiratory drive to the point of apnea. In these patients alternative non-opioid analgesics should be considered, and opioids should be employed only under careful medical supervision at the lowest effective dose.

Head Injury

OxyContin may cause severe hypotension. There is an added risk to individuals whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs such as phenothiazines or other agents which compromise vasomotor tone. Oxycodone may produce orthostatic hypotension in ambulatory patients. OxyContin (oxycodone), like all opioid analgesics of the morphine-type, should be administered with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure.

Hypotensive Effect

OxyContin and Alcohol Interaction

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.

OxyContin Drug Interactions

Opioid analgesics, including OxyContin (oxycodone), may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.

Oxycodone is metabolized in part to oxymorphone via cytochrome P450 2D6. While this pathway may be blocked by a variety of drugs (e.g., certain cardiovascular drugs including amiodarone and quinidine as well as polycyclic antidepressants), such blockade has not yet been shown to be of clinical significance with this agent. Clinicians should be aware of this possible interaction when administering OxyContin (oxycodone), however.

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