Endone

Endone HCl (Endone) 5 mg: Each capsule contains 4.5 mg of Endone as 5 mg of Endone HCl.

Endone HCl (Endone) 10 mg: Each capsule contains 9 mg of Endone as 10 mg of Endone HCl.

Endone HCl (Endone) Injection: Each mL contains 9 mg of Endone as 10 mg Endone HCl.

Excipients/Inactive Ingredients: Capsule: Cellulose microcrystalline, magnesium stearate, sunset yellow, titanium dioxide, red iron oxide, indigo carmine, yellow iron oxide, sodium laurylsulfate, and gelatin.

The capsules are printed with ink containing shellac, iron oxide and propylene glycol.

Injection: Sodium citrate, citric acid monohydrate, sodium chloride, hydrochloric acid, sodium hydroxide, water for injection.

Endone prolonged-release tablets (Endone) are approved for the treatment of moderate to severe pain including steady pain, e.g., cancer pain, paroxysmal spontaneous pain and allodynia. This prolonged-release oral formulation of Endone is indicated for the management of moderate to severe pain when a continuous, around-the-clock analgesic is needed for an extended period of time. Endone prolonged-release tablet (Endone) 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.

Endone prolonged-release tablet (Endone) 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. Endone prolonged-release tablets (Endone) is only indicated for post-operative use if the patient is already receiving the drug prior to surgery or if the post-operative 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.

Endone (Endone) is an opioid pain medication. An opioid is sometimes called a narcotic.

Endone is used to treat moderate to severe pain that is expected to last for an extended period of time. Endone is used for around-the-clock treatment of pain. It is not to be used on an "as-needed" basis for pain.

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

Important Dosage And Administration Instructions

Endone should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

Endone single doses greater than 36 mg (equivalent to 40 mg Endone [HCl]) or a total daily dose greater than 72 mg (equivalent to 80 mg Endone HCl) are to be administered only to patients in whom tolerance to an opioid of comparable potency has been established. Patients considered opioid tolerant are those receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral Endone HCl per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid.

Endone is administered, twice daily, every 12 hours, and must be taken with food. Instruct patients to take Endone capsules with approximately the same amount of food for every dose in order to ensure consistent plasma levels are achieved..

Patients who are unable to swallow Endone should be instructed to sprinkle the capsule contents on soft foods or into a cup and then administer directly into the mouth and immediately swallow. Endone may also be administered through a gastrostomy or nasogastric feeding tube.

• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.
• Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse.
• Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with Endone and adjust the dosage accordingly.

The maximum daily dose of Endone is 288 mg per day (eight 36 mg capsules, equivalent to 320 mg Endone HCl per day) as the safety of the excipients in Endone for doses over 288 mg/day has not been established.

Endone is formulated with Endone base. The following table describes the equivalent amount of Endone HCl present in other Endone products.

Equivalence table for dosage strengths of Endone salt and Endone base (Endone)

Initial Dosing

Use Of Endone As The First Opioid Analgesic (Opioid-Na

Endone interactions

See also:
What other drugs will affect Endone?

CNS Depressants

The concomitant use of Endone and other CNS depressants including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol can increase the risk of respiratory depression, profound sedation, coma, or death. Monitor patients receiving CNS depressants and Endone for signs of respiratory depression, sedation, and hypotension.

When combined therapy with any of the above medications is considered, the dose of one or both agents should be reduced.

Drugs Affecting Cytochrome P450 Isoenzymes

Inhibitors Of CYP3A4 And 2D6

Because the CYP3A4 isoenzyme plays a major role in the metabolism of Endone, drugs that inhibit CYP3A4 activity may cause decreased clearance of Endone which could lead to an increase in Endone plasma concentrations and result in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of CYP2D6 and 3A4 inhibitors. If co-administration with Endone is necessary, monitor patients for respiratory depression and sedation at frequent intervals and consider dose adjustments until stable drug effects are achieved.

Inducers Of CYP3A4

CYP450 3A4 inducers may induce the metabolism of Endone and, therefore, may cause increased clearance of the drug which could lead to a decrease in Endone plasma concentrations, lack of efficacy or, possibly, development of an abstinence syndrome in a patient who had developed physical dependence to Endone. If co-administration with Endone is necessary, monitor for signs of opioid withdrawal and consider dose adjustments until stable drug effects are achieved.

After stopping the treatment of a CYP3A4 inducer, as the effects of the inducer decline, the Endone plasma concentration will increase which could increase or prolong both the therapeutic and adverse effects, and may cause serious respiratory depression.

Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics

Mixed agonist/antagonist (i.e., pentazocine, nalbuphine, and butorphanol) and partial agonist (buprenorphine) analgesics may reduce the analgesic effect of Endone or precipitate withdrawal symptoms. Avoid the use of mixed agonist/antagonist and partial agonist analgesics in patients receiving Endone.

Muscle Relaxants

Endone may enhance the neuromuscular blocking action of true skeletal muscle relaxants and produce an increased degree of respiratory depression. Monitor patients receiving muscle relaxants and Endone for signs of respiratory depression that may be greater than otherwise expected.

Diuretics

Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Opioids may also lead to acute retention of urine by causing spasm of the sphincter of the bladder, particularly in men with enlarged prostates.

Anticholinergics

Anticholinergics or other medications with anticholinergic activity when used concurrently with opioid analgesics may result in increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor patients for signs of urinary retention or reduced gastric motility when Endone is used concurrently with anticholinergic drugs.

Drug Abuse And Dependence

Controlled Substance

Endone contains Oxycodone, a Schedule II controlled substance with a high potential for abuse similar to other opioids including fentanyl, hydromorphone, methadone, morphine, and oxymorphone. Endone can be abused and is subject to misuse, addiction, and criminal diversion.

The high drug content in extended-release formulations adds to the risk of adverse outcomes from abuse and misuse.

Abuse

All patients treated with opioids require careful monitoring for signs of abuse and addiction, since use of opioid analgesic products carries the risk of addiction even under appropriate medical use.

Drug abuse is the intentional non-therapeutic use of an over-the-counter or prescription drug, even once, for its rewarding psychological or physiological effects. Drug abuse includes, but is not limited to, the following examples: the use of a prescription or over-the-counter drug to get “high”, or the use of steroids for performance enhancement and muscle build up.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and include: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.

“Drug-seeking” behavior is very common to addicts and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated claims of loss of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” (visiting multiple prescribers) to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction.

Endone, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful recordkeeping of prescribing information, including quantity, frequency, and renewal requests as required by state law, is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to reduce abuse of opioid drugs.

Risks Specific To Abuse Of Endone

Endone is for oral use only. Abuse of Endone poses a risk of overdose and death. The risk is increased with concurrent use of Endone with alcohol and other central nervous system depressants. Taking cut, broken, chewed, crushed, or dissolved Endone enhances drug release and increases the risk of overdose and death.

With parenteral abuse, the inactive ingredients in Endone can be expected to result in local tissue necrosis, infection, pulmonary granulomas, and increased risk of endocarditis and valvular heart injury.

Parenteral drug abuse is commonly associated with transmission of infectious diseases, such as hepatitis and HIV.

Abuse Deterrence Studies

Endone is formulated with inactive ingredients intended to make the tablet more difficult to manipulate for misuse and abuse. For the purposes of describing the results of studies of the abusedeterrent characteristics of Endone resulting from a change in formulation, in this section, the original formulation of Endone, which is no longer marketed, will be referred to as “original Endone” and the reformulated, currently marketed product will be referred to as “Endone”.

In Vitro Testing

In vitro physical and chemical tablet manipulation studies were performed to evaluate the success of different extraction methods in defeating the extended-release formulation. Results support that, relative to original Endone, there is an increase in the ability of Endone to resist crushing, breaking, and dissolution using a variety of tools and solvents. The results of these studies also support this finding for Endone relative to an immediate-release Endone. When subjected to an aqueous environment, Endone gradually forms a viscous hydrogel (i.e., a gelatinous mass) that resists passage through a needle.

Clinical Studies

In a randomized, double-blind, placebo-controlled 5-period crossover pharmacodynamic study, 30 recreational opioid users with a history of intranasal drug abuse received intranasally administered active and placebo drug treatments. The five treatment arms were finely crushed Endone 30 mg tablets, coarsely crushed Endone 30 mg tablets, finely crushed original Endone 30 mg tablets, powdered Endone HCl 30 mg, and placebo. Data for finely crushed Endone, finely crushed original Endone, and powdered Endone HCl are described below.

Drug liking was measured on a bipolar drug liking scale of 0 to 100 where 50 represents a neutral response of neither liking nor disliking, 0 represents maximum disliking and 100 represents maximum liking. Response to whether the subject would take the study drug again was also measured on a bipolar scale of 0 to 100 where 50 represents a neutral response, 0 represents the strongest negative response (“definitely would not take drug again”) and 100 represents the strongest positive response (“definitely would take drug again”).

Twenty-seven of the subjects completed the study. Incomplete dosing due to granules falling from the subjects' nostrils occurred in 34% (n = 10) of subjects with finely crushed Endone, compared with 7% (n = 2) of subjects with finely crushed original Endone and no subjects with powdered Endone HCl.

The intranasal administration of finely crushed Endone was associated with a numerically lower mean and median drug liking score and a lower mean and median score for take drug again, compared to finely crushed original Endone or powdered Endone HCl as summarized in Table 4.

Table 4: Summary of Maximum Drug Liking (Emax) Data Following Intranasal Administration

The results of a similar analysis of drug liking for finely crushed Endone relative to finely crushed original Endone were comparable to the results of finely crushed Endone relative to powdered Endone HCl. Approximately 43% (n = 12) of subjects had no reduction in liking with Endone relative to original Endone. Approximately 57% (n = 16) of subjects had some reduction in drug liking, 36% (n = 10) of subjects had a reduction of at least 30% in drug liking, and approximately 29% (n = 8) of subjects had a reduction of at least 50% in drug liking with Endone compared to original Endone.

Summary

The in vitro data demonstrate that Endone has physicochemical properties expected to make abuse via injection difficult. The data from the clinical study, along with support from the in vitro data, also indicate that Endone has physicochemical properties that are expected to reduce abuse via the intranasal route. However, abuse of Endone by these routes, as well as by the oral route, is still possible.

Additional data, including epidemiological data, when available, may provide further information on the impact of the current formulation of Endone on the abuse liability of the drug. Accordingly, this section may be updated in the future as appropriate.

Endone contains Oxycodone, an opioid agonist and Schedule II controlled substance with an abuse liability similar to other opioid agonists, legal or illicit, including fentanyl, hydromorphone, methadone, morphine, and oxymorphone. Endone can be abused and is subject to misuse, addiction, and criminal diversion.

Dependence

Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity, e.g., naloxone, nalmefene, mixed agonist/antagonist analgesics (pentazocine, butorphanol, nalbuphine), or partial agonists (buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.

Endone should not be abruptly discontinued. If Endone is abruptly discontinued in a physically-dependent patient, an abstinence syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs.

See also:
What is the most important information I should know about Endone?

Endone may be habit forming. Never share Endone with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it.

Do not drink alcohol while you are taking Endone. 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 Endone in larger amounts, or 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.

This medication may impair your thinking or reactions. Avoid driving or operating machinery until you know how Endone will affect you.

Do not stop using Endone suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using Endone.

Use Endone sustained-release tablets as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Endone sustained-release tablets comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Endone sustained-release tablets refilled.
• Take Endone sustained-release tablets by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation.
• Swallow Endone sustained-release tablets whole. Do not break, crush, chew, dissolve, or split before swallowing.
• Some patients have reported trouble swallowing Endone sustained-release tablets. These reports have included choking, gagging, spitting tablets back up, and getting tablets stuck in the throat. To decrease these risks, take Endone sustained-release tablets 1 tablet at a time if your dose calls for more than 1 tablet. Do not pre-soak, lick, or wet the tablet before you place it in your mouth. Take each tablet with enough water to be sure that you swallow it completely. Swallow Endone sustained-release tablets immediately after you place it in your mouth.
• Take Endone sustained-release tablets on a regular schedule to get the most benefit from it. It is more effective in preventing pain than in treating pain after it occurs.
• Tell your doctor if your pain gets worse or if you have breakthrough pain while taking Endone sustained-release tablets.
• Do not suddenly stop taking Endone sustained-release tablets. You may experience withdrawal symptoms. If you need to stop Endone sustained-release tablets, your doctor will gradually lower your dose.
• If Endone sustained-release tablets is no longer needed, dispose of it as soon as possible by flushing it down the toilet. You may also check with your pharmacist for other ways to dispose of Endone sustained-release tablets.
• If you miss a dose of Endone sustained-release tablets, take it as soon as possible. Take your next dose 12 hours later. Do not take 2 doses at once. Call your doctor if you miss a dose and you are not sure what to do.

Ask your health care provider any questions you may have about how to use Endone sustained-release tablets.

This medication is used to help relieve moderate to severe pain. Endone belongs to a class of drugs known as opioid (narcotic) analgesics. It works in the brain to change how your body feels and responds to pain.

How to use Endone

If you are using Endone oral solution, read the Medication Guide provided by your pharmacist before you start using Endone oral solution and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

Take this medication by mouth as directed by your doctor. You may take this drug with or without food. If you have nausea, it may help to take this drug with food. Ask your doctor or pharmacist about other ways to decrease nausea (such as lying down for 1 to 2 hours with as little head movement as possible).

If you are using the liquid form of this medication, carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose. Ask your doctor or pharmacist if you are not sure how to check or measure the dose.

The dosage is based on your medical condition and response to treatment. Do not increase your dose, take the medication more frequently, or take it for a longer time than prescribed. Properly stop the medication when so directed.

Pain medications work best if they are used when the first signs of pain occur. If you wait until the pain has worsened, the medication may not work as well.

If you have ongoing pain (such as due to cancer), your doctor may direct you to also take long-acting opioid medications. In that case, this medication might be used for sudden (breakthrough) pain only as needed. Other pain relievers (such as acetaminophen, ibuprofen) may also be prescribed with this medication. Ask your doctor or pharmacist about using Endone safely with other drugs.

This medication may cause withdrawal reactions, especially if it has been used regularly for a long time or in high doses. In such cases, withdrawal symptoms (such as restlessness, watering eyes, runny nose, nausea, sweating, muscle aches) may occur if you suddenly stop using this medication. To prevent withdrawal reactions, your doctor may reduce your dose gradually. Ask your doctor or pharmacist for more details, and report any withdrawal reactions right away.

When this medication is used for a long time, it may not work as well. Talk with your doctor if this medication stops working well.

Along with its benefits, this medication may rarely cause abnormal drug-seeking behavior (addiction). This risk may be increased if you have abused alcohol or drugs in the past. Take this medication exactly as prescribed to lessen the risk of addiction.

Tell your doctor if your pain persists or worsens.

See also:
What are the possible side effects of Endone?

The safety of Endone prolonged-release tablets (Endone) was evaluated in double-blind clinical trials involving 713 patients with moderate to severe pain of various etiologies. In open-label studies of cancer pain, 187 patients received Endone prolonged-release tablets (Endone) in total daily doses ranging from 20 mg to 640 mg per day. The average total daily dose was approximately 105 mg per day.

Serious adverse reactions which may be associated with Endone prolonged-release tablet (Endone) therapy in clinical use are those observed with other opioid analgesics, including respiratory depression, apnea, respiratory arrest, and (to an even lesser degree) circulatory depression, hypotension, or shock.

The non-serious adverse events seen on initiation of therapy with Endone prolonged-release tablets (Endone) are typical opioid side effects. These events are dose-dependent, and their frequency depends upon the dose, the clinical setting, the patient's level of opioid tolerance, and host factors specific to the individual. They should be expected and managed as a part of opioid analgesia. The most frequent (>5%) include: constipation, nausea, somnolence, dizziness, vomiting, pruritus, headache, dry mouth, sweating, and asthenia. In many cases the frequency of these events during initiation of therapy may be minimized by careful individualization of starting dosage, slow titration, and the avoidance of large swings in the plasma concentrations of the opioid.

Many of these adverse events will cease or decrease in intensity as Endone prolonged-release tablets (Endone) therapy is continued and some degree of tolerance is developed. Clinical trials comparing Endone prolonged-release tablets (Endone) with immediate-release Endone and placebo revealed a similar adverse event profile between Endone prolonged-release tablets (Endone) and immediate-release Endone. The most common adverse events (>5%) reported by patients at least once during therapy were: See Table 5.

The following adverse experiences were reported in Endone prolonged-release tablets (Endone) treated patients with an incidence between 1% and 5%. In descending order of frequency they were anorexia, nervousness, insomnia, fever, confusion, diarrhea, abdominal pain, dyspepsia, rash, anxiety, euphoria, dyspnea, postural hypotension, chills, twitching, gastritis, abnormal dreams, thought abnormalities, and hiccups. The following adverse reactions occurred in less than 1% of patients involved in clinical trials or were reported in post marketing experience:

General: Accidental injury, chest pain, facial edema, malaise, neck pain, pain, allergic reactions, anaphylaxis, anaphylactoid reactions, drug dependence.

Cardiovascular: Migraine, syncope, vasodilation, ST depression.

Digestive: Dysphagia, eructation, flatulence, gastrointestinal disorder, increased appetite, nausea and vomiting, stomatitis, ileus.

Hemic and Lymphatic: Lymphadenopathy.

Metabolic and Nutritional: Dehydration, edema, hyponatremia, peripheral edema, syndrome of inappropriate antidiuretic hormone secretion, thirst.

Nervous: Abnormal gait, agitation, amnesia, depersonalization, depression, emotional lability, hallucination, hyperkinesia, hypesthesia, hypotonia, malaise, paresthesia, unvoluntary muscle contraction seizures, speech disorder, stupor, tinnitus, tremor, vertigo, withdrawal syndrome with or without seizures, hypertonia.

Respiratory: Cough increased, pharyngitis, voice alteration.

Skin: Dry skin, exfoliative dermatitis, urticaria.

Special Senses: Abnormal vision, miosis, taste perversion.

Urogenital: Amenorrhea, decreased libido, dysuria, hematuria, impotence, polyuria, urinary retention, impaired urination.