Oxycodone HCl
WARNING
OxyContin® is an opioid agonist and a Schedule II controlled substance with an abuse liability similar to morphine.
Oxycodone can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing OxyContin® in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.
OxyContin® 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® tablets are NOT intended for use as a prn analgesic.
OxyContin® 80 mg and 160 mg Tablets ARE FOR USE IN OPIOID TOLERANT PATIENTS ONLY. These tablet strengths may cause fatal respiratory depression when administered to patients not previously exposed to opioids.
OxyContin® (oxycodone hydrochloride controlled-release) TABLETS ARE TO BE SWALLOWED WHOLE AND ARE NOT TO BE BROKEN, CHEWED, OR CRUSHED. TAKING BROKEN, CHEWED, OR CRUSHED OxyContin® TABLETS LEADS TO RAPID RELEASE AND ABSORPTION OF A POTENTIALLY FATAL DOSE OF OXYCODONE.
OxyContin® (oxycodone hydrochloride controlled-release) tablets are an opioid analgesic supplied in 10 mg, 20 mg, 40 mg, 80 mg, and 160 mg tablet strengths for oral administration. The tablet strengths describe the amount of oxycodone per tablet as the hydrochloride salt.
Its molecular formula is C18H21NO4 · HCl. Its molecular weight is 351.83.
The chemical formula is 4, 5-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one hydrochloride.
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, hydroxypropyl methylcellulose, lactose, magnesium stearate, povidone, red iron oxide (20 mg strength tablet only), stearyl alcohol, talc, titanium dioxide, triacetin, yellow iron oxide (40 mg strength tablet only), yellow iron oxide with FD&C blue No.2 (80 mg strength tablet only), FD&C blue No.2 (160 mg strength tablet only) and other ingredients.
INDICATIONS
OxyContin® 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.
Physicians should individualize treatment in every case, initiating therapy at the appropriate point along a progression from non-opioid analgesics, such as nonsteroidal anti-inflammatory drugs and acetaminophen to opioids in a plan of pain management such as outlined by the World Health Organization, the Agency for Health 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.
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. (See American Pain Society guidelines.)
DOSAGE AND ADMINISTRATION
General Principles
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 ANALGESIA, 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. TAKING 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 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 (see Special Instructions for OxyContin® 80 mg and 160 mg 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 (see CLINICAL PHARMACOLOGY: PHARMACOKINETICS AND METABOLISM). While symmetric (same dose AM and PM), around-the-clock, q12h dosing is appropriate for the majority of patients, some patients may benefit from asymmetric (different 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 [See BOXED WARNING].
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:
(1) the general condition and medical status of the patient;
(2) the daily dose, potency, and kind of the analgesic(s) the patient has been taking;
(3) the reliability of the conversion estimate used to calculate the dose of oxycodone;
(4) the patient's opioid exposure and opioid tolerance (if any);
(5) 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
(6) 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 (see
drug INTERACTIONS).
For initiation of OxyContin® therapy for patients previously taking opioids, the conversion ratios from Foley, KM. [NEJM, 1985; 313:84-95], found below, 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.
1. Using standard conversion ratio estimates (see Table 4 below), multiply the mg/day of the previous opioids by the appropriate multiplication factors to obtain the equivalent total daily dose of oral oxycodone.
2. When converting from oxycodone, divide the 24-hour oxycodone dose in half to obtain the twice a day (q12h) dose of OxyContin®.
3. 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).
4. Discontinue all other around-the-clock opioid drugs when OxyContin® therapy is initiated.
5. No fixed conversion ratio is likely to be satisfactory in all patients, especially patients receiving large opioid doses. The recommended doses shown in Table 4 are only a starting point, and close observation and frequent titration are indicated until patients are stable on the new therapy.
Table 4
Multiplication Factors for Converting the Daily Dose of
Prior Opioids to the Daily Dose of Oral Oxycodone*
(Mg/Day Prior Opioid x Factor = Mg/Day Oral Oxycodone)
Oral Prior Opioid Parenteral Prior Opioid
Oxycodone 1 —
Codeine 0.15 —
Hydrocodone 0.9 —
Hydromorphone 4 20
Levorphanol 7.5 15
Meperidine 0.1 0.4
Methadone 1.5 3
Morphine 0.5 3
To be used only for conversion to oral oxycodone. For patients receiving high-dose parenteral opioids, a more conservative conversion is warranted. For example, for high-dose parenteral morphine, use 1.5 instead of 3 as a multiplication factor.
In all cases, supplemental analgesia (see below) should be made available in the form of a suitable short-acting analgesic.
OxyContin® can be safely used concomitantly with usual doses of non-opioid analgesics and analgesic adjuvants, provided care is taken to select a proper initial dose (see PRECAUTIONS).
Conversion from Transdermal Fentanyl to OxyContin®
Eighteen hours following the removal of the transdermal fentanyl patch, OxyContin® treatment can be initiated. Although there has been no systematic assessment of such conversion, a conservative oxycodone dose, approximately 10 mg q12h of OxyContin®, should be initially substituted for each 25 µg/hr fentanyl transdermal patch. The patient should be followed closely for early titration, as there is very limited clinical experience with this conversion.
Managing Expected Opioid Adverse Experiences
Most patients receiving opioids, especially those who are opioid-naive, will experience side effects. Frequently the side effects from OxyContin® are transient, but may require evaluation and management. Adverse events such as constipation should be anticipated and treated aggressively and prophylactically with a stimulant laxative and/or stool softener. Patients do not usually become tolerant to the constipating effects of opioids.
Other opioid-related side effects such as sedation and nausea are usually self-limited and often do not persist beyond the first few days. If nausea persists and is unacceptable to the patient, treatment with anti-emetics or other modalities may relieve these symptoms and should be considered.
Patients receiving OxyContin® may pass an intact matrix "ghost" in the stool or via colostomy. These ghosts contain little or no residual oxycodone and are of no clinical consequence.
Individualization of Dosage
Once 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 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 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 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.
Conversion from OxyContin® to Parenteral Opioids
To avoid overdose, conservative dose conversion ratios should be followed.
SAFETY AND HANDLING
OxyContin® (oxycodone HCl controlled-release) tablets are solid dosage forms that contain oxycodone which is a controlled substance. Like morphine, oxycodone is controlled under Schedule II of the Controlled Substances Act. OxyContin® has been targeted for theft and diversion by criminals. 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.
HOW SUPPLIED
OxyContin® (oxycodone hydrochloride controlled-release) 10 mg tablets are round, unscored, white-colored, convex tablets bearing the symbol OC on one side and 10 on the other. They are supplied as follows:
NDC 59011-100-10: child-resistant closure, opaque plastic bottles of 100
NDC 59011-100-25: unit dose packaging with 25 individually numbered tablets per card; one card per glue end carton
OxyContin® (oxycodone hydrochloride controlled-release) 20 mg tablets are round, unscored, pink-colored, convex tablets bearing the symbol OC on one side and 20 on the other. They are supplied as follows:
NDC 59011-103-10: child-resistant closure, opaque plastic bottles of 100
NDC 59011-103-25: unit dose packaging with 25 individually numbered tablets per card; one card per glue end carton
OxyContin® (oxycodone hydrochloride controlled-release) 40 mg tablets are round, unscored, yellow-colored, convex tablets bearing the symbol OC on one side and 40 on the other. They are supplied as follows:
NDC 59011-105-10: child-resistant closure, opaque plastic bottles of 100
NDC 59011-105-25: unit dose packaging with 25 individually numbered tablets per card; one card per glue end carton
OxyContin® (oxycodone hydrochloride controlled-release) 80 mg tablets are round, unscored, green-colored, convex tablets bearing the symbol OC on one side and 80 on the other. They are supplied as follows:
NDC 59011-107-10: child-resistant closure, opaque plastic bottles of 100
NDC 59011-107-25: unit dose packaging with 25 individually numbered tablets per card; one card per glue end carton
OxyContin® (oxycodone hydrochloride controlled-release) 160 mg tablets are caplet-shaped, unscored, blue-colored, convex tablets bearing the symbol OC on one side and 160 on the other. They are supplied as follows:
NDC 59011-109-10: child-resistant closure, opaque plastic bottles of 100
NDC 59011-109-25: unit dose packaging with 25 individually numbered tablets per card; one card per glue end carton
Store at 25°C (77 F); excursions permitted between 15°-30°C (59°-86°F).
Dispense in tight, light-resistant container.
Healthcare professionals can telephone Purdue Pharma’s Medical Services Department (1-888-726-7535) for information on this product.
PATIENT INFORMATION
If clinically advisable, patients receiving OxyContin® (oxycodone hydrochloride controlled-release) tablets or their caregivers should be given the following information by the physician, nurse, pharmacist, or caregiver:
1. Patients should be aware that OxyContin® tablets contain oxycodone, which is a morphine-like substance.
2. Patients should be advised that OxyContin® tablets were designed to work properly only if swallowed whole. OxyContin® tablets will release all their contents at once if broken, chewed, or crushed, resulting in a risk of fatal overdose.
3. Patients should be advised to report episodes of breakthrough pain and adverse experiences occurring during therapy. Individualization of dosage is essential to make optimal use of this medication.
4. Patients should be advised not to adjust the dose of OxyContin® without consulting the prescribing professional.
5. 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).
6. 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.
7. Women of childbearing potential who become, or are planning to become, pregnant should be advised to consult their physician regarding the effects of analgesics and other
drug use during pregnancy on themselves and their unborn child.
8. Patients should be advised that OxyContin® is a potential
drug of abuse. They should protect it from theft, and it should never be given to anyone other than the individual for whom it was prescribed.
9. Patients should be advised that they may pass empty matrix "ghosts" (tablets) via colostomy or in the stool, and that this is of no concern since the active medication has already been absorbed.
10. Patients should be advised that if they have been receiving treatment with OxyContin® for more than a few weeks and cessation of therapy is indicated, it may be appropriate to taper the OxyContin® dose, rather than abruptly discontinue it, due to the risk of precipitating withdrawal symptoms. Their physician can provide a dose schedule to accomplish a gradual discontinuation of the medication.
11. Patients should be instructed to keep OxyContin® in a secure place out of the reach of children. When OxyContin® is no longer needed, the unused tablets should be destroyed by flushing down the toilet.
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