Oxycodone Hcl (Generic) Tablets

OXYCODONE HCL.

THIS IS ORIGINAL TYPE "O.C." FORMULATION NOT THE "OP" FORMULA;  THIS ITEM AVAILABLE ON LIMITED QUANTITY FROM WHOLESALERS, THEREFORE INVENTORY IS FIRST COME-FIRST SERVE.

Oxycodone / Roxycodone hcl.
(Oxycodone HCl Controlled-Release) Tablets
 
    Oxycodone Hcl. Tablets, 80mg (oxycodone generic, opioid tolerant patients only)

Patient Education - English

• Generic Name: oxycodone

• Pronounced: ox i KOE done

• Brand Names: ETH-Oxydos, Oxyfast, OxyIR, Percolone, Roxicodone, Roxicodone Intensol, Targin, Targinact, Targinq

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Black Box Warnings 

Abuse Potential

Opioid agonist is a Schedule II controlled substance in the USA; therefore when prescribing or dispensing ER tablets consider abuse potential if concern about incr. risk of misuse, abuse, or diversion; incr. opioid abuse risk if personal or family hx of substance abuse or mental illness; assess clinical risk for opioid abuse or addiction prior to prescribing; monitor all pts for signs of misuse, abuse, or addiction

Extended-Release Formulation

only for mod-severe pain when continuous, around-the-clock analgesic needed for extended period; not for use as prn analgesic; swallow tablets whole, do not cut/crush/chew/dissolve as rapid release and absorption of potentially fatal oxycodone dose may occur

Tablet Strength and Dose Restriction

60 mg and 80 mg ER tabs, single doses >40 mg, or daily doses >80 mg for opioid tolerant pts only; use in opioid non-tolerant pts may cause fatal resp. depression; opioid tolerant if taking oral morphine >60 mg/day, transdermal fentanyl >25 mcg/h, oxycodone >30 mg/day, oral hydromorphone >8 mg/day, oral oxymorphone >25 mg/day, or equianalgesic dose of another opioid for >1wk

CYP450 3A4 inhibitors

concomitant use w/ CYP450 3A4 inhibitors incl. macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir) may incr. oxycodone conc. which may incr. or prolong adverse effects incl. potentially fatal resp. depression; monitor pts for extended period of time and adjust dose as needed

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PATIENT INFORMATION : Dosage Form: Controlled-Release Oxycodone round tablets (OX-i-KOE-done) OxyContin are used for: Treating moderate to severe pain. It may also be used for other conditions as determined by your doctor.

What is the most important information I should know about oxycodone?

Oxycodone may be habit-forming and should be used only by the person it was prescribed for. Oxycodone should never be shared with another person, especially someone who has a history of drug abuse or addiction. Keep the medication in a secure place where others cannot get to it.

Do not drink alcohol while you are taking oxycodone. Dangerous side effects or death can occur when alcohol is combined with a narcotic pain medicine. Check your food and medicine labels to be sure these products do not contain alcohol.

Never take more than your prescribed dose of oxycodone. Tell your doctor if the medicine seems to stop working as well in relieving your pain.

Oxycodone can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Do not stop using oxycodone suddenly, or you could have unpleasant withdrawal symptoms. Talk to your doctor about how to avoid withdrawal symptoms when stopping the medication.

What is oxycodone?

Oxycodone is in a group of drugs called narcotic pain relievers. It is similar to morphine.

Oxycodone is used to treat moderate to severe pain. The extended-release form of this medication is for around-the-clock treatment of pain. Oxycodone is not for treating pain just after a surgery unless you were already taking oxycodone before the surgery.

Oxycodone may also be used for other purposes not listed in this medication guide.

What should I discuss with my healthcare provider before using oxycodone?

Do not use this medication if you have ever had an allergic reaction to a narcotic medicine (examples include methadone, morphine, Oxycontin, Darvocet, Percocet, Vicodin, Lortab, and many others), or to a narcotic cough medicine that contains codeine, hydrocodone, or dihydrocodeine.

You should also not take oxycodone if you are having an asthma attack or if you have a bowel obstruction called paralytic ileus.

Oxycodone may be habit-forming and should be used only by the person it was prescribed for. Oxycodone should never be shared with another person, especially someone who has a history of drug abuse or addiction. Keep the medication in a secure place where others cannot get to it.

Before using oxycodone, tell your doctor if you are allergic to any drugs, or if you have:

• asthma, COPD, sleep apnea, or other breathing disorders;
• liver or kidney disease;
• underactive thyroid;
• curvature of the spine;
• a history of head injury or brain tumor;
• epilepsy or other seizure disorder;
• low blood pressure;
• gallbladder disease;
• Addison's disease or other adrenal gland disorders;
• enlarged prostate, urination problems;
• mental illness; or
• a history of drug or alcohol addiction.

FDA pregnancy category C. This medication may be harmful to an unborn baby, and could cause addiction or withdrawal symptoms in a newborn. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

Oxycodone can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Older adults may be more sensitive to the effects of this medicine.

How should I use oxycodone?

Take this medication exactly as it was prescribed for you. Never take oxycodone in larger amounts, or use it for longer than recommended by your doctor. Follow the directions on your prescription label. Tell your doctor if the medicine seems to stop working as well in relieving your pain.

Take the pill form of this medicine with a full glass of water.

Do not crush, chew, or break an extended-release tablet. Swallow the pill whole. It will release medicine slowly in the body. Breaking the pill would cause too much of the drug to be released at one time.

Measure the liquid form of oxycodone with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist where you can get one.

Drink plenty of water daily to help prevent constipation while you are using oxycodone. Ask your doctor about ways to increase the fiber in your diet. Do not use a stool softener (laxative) without first asking your doctor.

Do not stop using oxycodone suddenly, or you could have unpleasant withdrawal symptoms. Talk to your doctor about how to avoid withdrawal symptoms when stopping the medication.

Never crush a tablet or other pill to mix into a liquid for injecting the drug into your vein. This practice has resulted in death with the misuse of oxycodone and similar prescription drugs.

Store this medication at room temperature, away from heat, moisture, and light.

Keep track of how many pills have been used from each new bottle of this medicine. Oxycodone is a drug of abuse and you should be aware if any person in the household is using this medicine improperly or without a prescription.

After you have stopped using this medication, flush any unused pills down the toilet.

Throw away any unused liquid oxycodone that is older than 90 days.

What happens if I miss a dose?

Since oxycodone is sometimes used as needed, you may not be on a dosing schedule. If you are using the medication regularly, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and wait until your next regularly scheduled dose. Do not use extra medicine to make up the missed dose.

Extended-release oxycodone is not for use on an as-needed basis for pain.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine. An overdose of oxycodone can be fatal.

Overdose symptoms may include extreme drowsiness, muscle weakness, confusion, cold and clammy skin, pinpoint pupils, shallow breathing, slow heart rate, fainting, or coma.

What should I avoid while using oxycodone?

Do not drink alcohol while you are taking this medication. Dangerous side effects or death can occur when alcohol is combined with oxycodone. Check your food and medicine labels to be sure these products do not contain alcohol.

Oxycodone can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

What are the possible side effects of oxycodone?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

• shallow breathing, slow heartbeat;
• seizure (convulsions);
• cold, clammy skin;
• confusion;
• severe weakness or dizziness; or
• feeling light-headed, fainting.

Less serious side effects are more likely to occur, such as:

• nausea, vomiting, constipation, loss of appetite;
• dizziness, headache, tired feeling;
• dry mouth;
• sweating; or
• itching.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect oxycodone?

Do not take oxycodone with alcohol, other narcotic pain medications, sedatives, tranquilizers, muscle relaxers, or other medicines that can make you sleepy or slow your breathing. Dangerous side effects may result.

Before taking oxycodone, tell your doctor if you are using pentazocine (Talwin), nalbuphine (Nubain), butorphanol (Stadol), or buprenorphine (Buprenex, Subutex). If you are using any of these drugs, you may not be able to use oxycodone, or you may need dosage adjustments or special tests during treatment.

This list is not complete and there may be other drugs that can interact with oxycodone. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about oxycodone.

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Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Pill Pictures

	oxycodone (generic) 80 mg
oxycodone (generic) 30 mg	oxycodone (generic) 20 mg
oxycodone (generic) 10 mg	oxycodone (generic) 20 mg
oxycodone (generic) 20 mg	oxycodone (generic) 40 mg
oxycodone (generic) 40 mg	oxycodone (generic) 80 mg
oxycodone (generic) 30 mg	oxycodone (generic) 30 mg
oxycodone (generic) 30 mg	oxycodone (generic) 15 mg
oxycodone (generic) 15 mg	oxycodone (generic) 15 mg
oxycodone (generic) 15 mg	oxycodone (generic) 15 mg
oxycodone (generic) 15 mg	OxyContin (oxycodone) 80 mg
OxyContin (oxycodone) 40 mg	OxyContin (oxycodone) 15 mg
OxyContin (oxycodone) 30 mg	OxyContin (oxycodone) 60 mg
OxyContin (oxycodone) 10 mg	OxyContin (oxycodone) 20 mg
OxyIR (oxycodone) 5 mg	Roxicodone (oxycodone) 15 mg
Roxicodone (oxycodone) 30 mg	Roxicodone (oxycodone) 5 mg

* 80 mg and 160 mg for use in opioid-tolerant patients only

Read this information carefully before you take OxyContin® (ox-e-CON-tin) tablets. Also read the information you get with your refills. There may be something new. This information does not take the place of talking with your doctor about your medical condition or your treatment. Only you and your doctor can decide if OxyContin is right for you. Share the important information in this leaflet with members of your household.

Oxycontin vs Oxycodone

A number of people wonder if there is a difference between oxycontin and oxycodone. Are they the same medicines? Is oxycodone just a generic name for oxycontin? We’ll address these questions and other differences between the two:

• Oxycodone hydrochloride is an opioid painkiller. It can be found in a number of prescription medications. When it is available by itself, it is available in the form of oxycontin. Oxycodone is also found in combination with other ingredients on a number of prescription medications e.g. Percocet.

• The main difference between the two relates to the onset of action. Oxycontin is a time released drug. This means that it acts over a period of time. Usually, oxycodone medications need to be taken every four to six hours. However, Oxycontin continues acting for at least 12 hours. That is why it needs to be taken only twice a day.

• You may come across certain articles that categorize oxycodone as a generic name for oxycontin because it is the active substance in the medication. However, it would be incorrect to say that because oxycodone is an active ingredient in other medications also. Most experts prefer calling oxycontin ‘oxycodone extended release’.

• The two medications are prepared in a different manner. Though oxycontin contains more of oxycodone, it is also prepared in a manner that releases the medication gradually into the blood. So, even though the dosage is large, it is released slowly into the blood stream. Oxycodone is often used together with other chemicals in other medications like Percocet.

• The dangers of over dosage in oxycontin are more pronounced. Since the amount of oxycodone is large, lack of a sustained release may have severe effects on the patient. This is especially true for first time users. The danger becomes more apparent in the case of addicts who break open the capsule and snort it in.

• A common problem with quick acting painkillers is that they become nearly ineffective within a few hours. The action peaks within a few minutes, but falls within a few hours. Oxycontin aims at doing away with this problem by going for a sustained release.

Summary:
1. Oxycontin is time released oxycodone. It is pure oxycodone, without anything added.
2. Oxycodone may remain effective for around 6 hours. However, oxycontin remains effective for around twelve hours also. This is because the medication is slowly released into the body.
3. Oxycodone may contain other chemicals like Tylenol, which may induce vomiting in a person if taken in large amounts. However, since oxycontin does not contain this chemical, it becomes more of a danger if taken in large amounts.
4. Oxycontin should never be broken up and taken in. It may cause severe and fatal after effects if taken in this manner.
5. There is no reduction in the efficacy of oxycontin during the entire time

What Is The Most Important Information I Should Know About OxyContin®?

• Use OxyContin the way your doctor tells you to.
• Use OxyContin only for the condition for which it was prescribed.
• OxyContin is not for occasional (“as needed”) use.
• Swallow the tablets whole. Do not break, crush, dissolve, or chew them before swallowing. OxyContin® works properly over 12 hours only when swallowed whole. If a tablet is broken, crushed, dissolved, or chewed, the entire 12 hour dose will be absorbed into your body all at once. This can be dangerous, causing an overdose, and possibly death.
• Keep OxyContin® out of the reach of children. Accidental overdose by a child is dangerous and may result in death.
• Prevent theft and misuse. OxyContin contains a narcotic painkiller that can be a target for people who abuse prescription medicines. Therefore, keep your tablets in a secure place, to protect them from theft. Never give them to anyone else. Selling or giving away this medicine is dangerous and against the law.

What is OxyContin®?

OxyContin® is a tablet that comes in several strengths and contains the medicine oxycodone (ox-e-KOE-done). This medicine is a painkiller like morphine. OxyContin treats moderate to severe pain that is expected to last for an extended period of time. Use OxyContin regularly during treatment. It contains enough medicine to last for up to twelve hours.

Who Should Not Take OxyContin®?

Do not take OxyContin® if

• your doctor did not prescribe OxyContin® for you.
• your pain is mild or will go away in a few days.
• your pain can be controlled by occasional use of other painkillers.
• you have severe asthma or severe lung problems.
• you have had a severe allergic reaction to codeine, hydrocodone, dihydrocodeine, or oxycodone (such as Tylox, Tylenol with Codeine, or Vicodin). A severe allergic reaction includes a severe rash, hives, breathing problems, or dizziness.
• you had surgery less than 12 - 24 hours ago and you were not taking OxyContin just before surgery.

Your doctor should know about all your medical conditions before deciding if OxyContin is right for you and what dose is best. Tell your doctor about all of your medical problems, especially the ones listed below:

• trouble breathing or lung problems
• head injury
• liver or kidney problems
• adrenal gland problems, such as Addison’s disease
• convulsions or seizures
• alcoholism
• hallucinations or other severe mental problems
• past or present substance abuse or drug addiction

If any of these conditions apply to you, and you haven’t told your doctor, then you should tell your doctor before taking OxyContin.

If you are pregnant or plan to become pregnant, talk with your doctor. OxyContin may not be right for you. Tell your doctor if you are breast feeding. OxyContin will pass through the milk and may harm the baby.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. They may cause serious medical problems when taken with OxyContin, especially if they cause drowsiness.

How Should I Take OxyContin®?

• Follow your doctor’s directions exactly. Your doctor may change your dose based on your reactions to the medicine. Do not change your dose unless your doctor tells you to change it. Do not take OxyContin more often than prescribed.
• Swallow the tablets whole. Do not break, crush, dissolve, or chew before swallowing. If the tablets are not whole, your body will absorb too much medicine at one time. This can lead to serious problems, including overdose and death.
• If you miss a dose, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once unless your doctor tells you to.
• In case of overdose, call your local emergency number or Poison Control Center right away.
• Review your pain regularly with your doctor to determine if you still need OxyContin.
• You may see tablets in your stools (bowel movements). Do not be concerned. Your body has already absorbed the medicine.

If you continue to have pain or bothersome side effects, call your doctor.

Stopping OxyContin. Consult your doctor for instructions on how to stop this medicine slowly to avoid uncomfortable symptoms. You should not stop taking OxyContin all at once if you have been taking it for more than a few days.

After you stop taking OxyContin, flush the unused tablets down the toilet.

What Should I Avoid While Taking OxyContin®?

• Do not drive, operate heavy machinery, or participate in any other possibly dangerous activities until you know how you react to this medicine. OxyContin can make you sleepy.
• Do not drink alcohol while using OxyContin. It may increase the chance of getting dangerous side effects.
• Do not take other medicines without your doctor’s approval. Other medicines include prescription and non-prescription medicines, vitamins, and supplements. Be especially careful about products that make you sleepy.

What are the Possible Side Effects of OxyContin®?

Call your doctor or get medical help right away if

• your breathing slows down
• you feel faint, dizzy, confused, or have any other unusual symptoms

Some of the common side effects of OxyContin® are nausea, vomiting, dizziness, drowsiness, constipation, itching, dry mouth, sweating, weakness, and headache. Some of these side effects may decrease with continued use.

There is a risk of abuse or addiction with narcotic painkillers. If you have abused drugs in the past, you may have a higher chance of developing abuse or addiction again while using OxyContin.

These are not all the possible side effects of OxyContin. For a complete list, ask your doctor or pharmacist.

General Advice About OxyContin

• Do not use OxyContin for conditions for which it was not prescribed.
• Do not give OxyContin to other people, even if they have the same symptoms you have. Sharing is illegal and may cause severe medical problems, including death.

This leaflet summarizes the most important information about OxyContin. If you would like more information, talk with your doctor. Also, you can ask your pharmacist or doctor for information about OxyContin that is written for health professionals.

©2002, 2004, 2005, 2007, Purdue Pharma L.P.

Purdue Pharma L.P.
Stamford, CT 06901-3431

January 15, 2007

OT00367J
300514-0G

How is OxyContin Supplied

OxyContin® (oxycodone hydrochloride controlled-release) Tablets 10 mg are round, unscored, white-colored, convex tablets imprinted with 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 59011-100-20: unit dose packaging with 10 individually numbered tablets per card; two cards per glue end carton

OxyContin® (oxycodone hydrochloride controlled-release) Tablets 20 mg are round, unscored, pink-colored, convex tablets imprinted with 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 59011-103-20: unit dose packaging with 10 individually numbered tablets per card; two cards per glue end carton

OxyContin® (oxycodone hydrochloride controlled-release) Tablets 40 mg are round, unscored, yellow-colored, convex tablets imprinted with 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 59011-105-20: unit dose packaging with 10 individually numbered tablets per card; two cards per glue end carton

OxyContin® (oxycodone hydrochloride controlled-release) Tablets 80 mg are round, unscored, convex tablets imprinted with 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
Non-NDC Export: packed 90 tablets in child resistant blister packs

OxyContin® (oxycodone hydrochloride controlled-release) Tablets 160 mg are caplet-shaped, unscored, blue-colored, convex tablets imprinted with 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 59011-109-20: unit dose packaging with 10 individually numbered tablets per card; two cards 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 for information on this product.

OxyContin is in a group of drugs called narcotic pain relievers. It is similar to morphine. OxyContin is in a group of drugs called narcotic pain relievers. It is similar to morphine.

Generic Name: oxycodone hydrochloride
Dosage Form: Controlled-Release Tablets CII

OxyContin Description

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. The structural formula for oxycodone hydrochloride is as follows:

The chemical formula is 4, 5α-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, hypromellose, lactose, magnesium stearate, polyethylene glycol 400, povidone, sodium hydroxide, sorbic acid, stearyl alcohol, talc, titanium dioxide, and triacetin.

The 10 mg tablets also contain: hydroxypropyl cellulose.

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

The 40 mg tablets also contain: polysorbate 80 and yellow iron oxide.

The 80 mg tablets also contain: FD&C blue No. 2, hydroxypropyl cellulose, and yellow iron oxide.

The 160 mg tablets also contain: FD&C blue No. 2 and polysorbate 80.

OxyContin - Clinical Pharmacology

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.

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 (See OVERDOSAGE).

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 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 (see DOSAGE AND ADMINISTRATION), because the effective analgesic dose for some patients will be too high to be tolerated by other pat ients.

PHARMACOKINETICS AND METABOLISM

The activity of OxyContin Tablets is primarily due to the parent drug oxycodone. OxyContin Tablets are designed to provide controlled delivery of oxycodone over 12 hours.

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

Oxycodone release from OxyContin Tablets is pH independent. Oxycodone is well absorbed from OxyContin Tablets with an oral bioavailability of 60% to 87%. The relative oral bioavailability of OxyContin 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 OxyContin® was 4.5 hours compared to 3.2 hours for immediate-release oxycodone.

Absorption

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 t½ of absorption is 0.4 hours for immediate-release oral oxycodone. In contrast, OxyContin 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.

Plasma Oxycodone by Time

Dose proportionality has been established for the 10 mg, 20 mg, 40 mg, and 80 mg tablet strengths for both peak plasma concentrations (Cmax) 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 (Cmax) and extent of absorption (AUC) (see Table 2 below). Given the short half-life of elimination of oxycodone from OxyContin®, steady-state plasma concentrations of oxycodone are achieved within 24-36 hours of initiation of dosing with OxyContin Tablets. In a study comparing 10 mg of OxyContin every 12 hours to 5 mg of immediate-release oxycodone every 6 hours, the two treatments were found to be equivalent for AUC and Cmax, and similar for Cmin (trough) concentrations. There was less fluctuation in plasma concentrations for the OxyContin Tablets than for the immediate-release formulation.

OxyContin® is NOT INDICATED FOR RECTAL ADMINISTRATION. Data from a study involving 21 normal volunteers show that OxyContin 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.

Food Effects

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

Distribution

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).

Metabolism

Oxycodone hydrochloride is extensively metabolized to noroxycodone, oxymorphone, and their glucuronides. The major circulating metabolite is noroxycodone with an AUC ratio of 0.6 relative to that of oxycodone. 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.

The formation of oxymorphone, but not noroxycodone, is mediated by cytochrome P450 2D6 and, as such, its formation can, in theory, be affected by other drugs (see Drug-Drug Interactions).

Excretion

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.

Special Populations

Elderly

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

Gender

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

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

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).

Drug-Drug Interactions (see PRECAUTIONS)

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.

Pharmacodynamics

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

Indications and Usage for OxyContin

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 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 HealthCare 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 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. OxyContin is 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.)

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.

Warnings

OxyContin 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 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 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.

Misuse, Abuse and Diversion of Opioids

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.

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 has 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.

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

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.

Interactions with Alcohol and Drugs of Abuse

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.