Oxycodone Hcl

Description

11 DESCRIPTION OXYCODONE HCl EXTENDED-RELEASE TABLETS are an opioid agonist supplied in 10 mg, 20 mg, 40 mg, and 80 mg tablets 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: C 18 H 21 NO 4 · HCl MW 351.83 The chemical name is 4, 5a-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 10 mg, 20 mg, 40 mg, and 80 mg tablets contain the following inactive ingredients: butylated hydroxytoluene (BHT), hypromellose, polyethylene glycol 400, polyethylene oxide, magnesium stearate, titanium dioxide. 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 hydroxypropyl cellulose, yellow iron oxide and FD&C Blue #2/Indigo Carmine Aluminum Lake. chemical structure

What Is Oxycodone Hcl Used For?

1 INDICATIONS AND USAGE OXYCODONE HCl EXTENDED-RELEASE TABLETS are indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate in: Adults; and Opioid-tolerant pediatric patients 11 years of age and older who are already receiving and tolerate a minimum daily opioid dose of at least 20 mg oxycodone orally or its equivalent. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations [see Warnings and Precautions (5.1) ] , reserve OXYCODONE HCl EXTENDED-RELEASE TABLETS for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. OXYCODONE HCl EXTENDED-RELEASE TABLETS are not indicated as an as-needed (prn) analgesic. OXYCODONE HCl EXTENDED-RELEASE TABLETS are an opioid agonist indicated for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate in: Adults; and Opioid-tolerant pediatric patients 11 years of age and older who are already receiving and tolerate a minimum daily opioid dose of at least 20 mg oxycodone orally or its equivalent. Limitations of Use Because of the risks of addiction, abuse and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve OXYCODONE HCl EXTENDED-RELEASE TABLETS for use in patients for whom alternative treatment options (e.g. non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain. (1) OXYCODONE HCl EXTENDED-RELEASE TABLETS are not indicated as an as-needed (prn) analgesic. (1)

Dosage and Administration

2 DOSAGE AND ADMINISTRATION To be prescribed only by healthcare providers knowledgeable in use of potent opioids for management of chronic pain. (2.1) OXYCODONE HCl EXTENDED-RELEASE TABLETS 60 mg and 80 mg tablets, a single dose greater than 40 mg, or a total daily dose greater than 80 mg are only for use in patients in whom tolerance to an opioid of comparable potency has been established. (2.1) Patients considered opioid-tolerant are those taking, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone 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. (2.1) Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals (2.1) . Individualize dosing based on the severity of pain, patient response, prior analgesic experience, and risk factors for addiction, abuse, and misuse. (2.1) Instruct patients to swallow tablets intact and not to cut, break, chew, crush, or dissolve tablets (risk of potentially fatal dose). (2.1 , 5.1) Instruct patients to take tablets one at a time, with enough water to ensure complete swallowing immediately after placing in mouth. (2.1 , 5.11) Discuss availability of naloxone with the patient and caregiver and assess each patient’s need for access to naloxone, both when initiating and renewing treatment with OXYCODONE HCl EXTENDED-RELEASE TABLETS. Consider prescribing naloxone based on the patient’s risk factors for overdose (2.2 , 5.1 , 5.3 , 5.6) . Do not abruptly discontinue OXYCODONE HCl EXTENDED-RELEASE TABLETS in a physically dependent patient because rapid discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. (2.10) Adults : For opioid-naïve and opioid non-tolerant patients, initiate with 10 mg tablets orally every 12 hours. See full prescribing information for instructions on conversion from opioids to oxycodone HCl extended-release, titration and maintenance of therapy. (2.3 , 2.4 , 2.6) Pediatric Patients 11 Years of Age and Older For use only in pediatric patients 11 years and older already receiving and tolerating opioids for at least 5 consecutive days with a minimum of 20 mg per day of oxycodone or its equivalent for at least two days immediately preceding dosing with oxycodone HCl extended-release. (2.5) See full prescribing information for instructions on conversion from opioids to oxycodone HCl extended-release, titration and maintenance of therapy. (2.5 , 2.6) Geriatric Patients : In debilitated, opioid non-tolerant geriatric patients, initiate dosing at one third to one half the recommended starting dosage and titrate carefully. (2.8 , 8.5) Patients with Hepatic Impairment : Initiate dosing at one third to one half the recommended starting dosage and titrate carefully. (2.9 , 8.6) 2.1 Important Dosage and Administration Instructions...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Addiction, Abuse, and Misuse [see Warnings and Precautions (5.1)] Life-Threatening Respiratory Depression [see Warnings and Precautions (5.3)] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.4)] Interactions With Benzodiazepines and Other CNS Depressants [see Warnings and Precautions (5.6)] Adrenal Insufficiency [see Warnings and Precautions (5.8)] Severe Hypotension [see Warnings and Precautions (5.9)] Gastrointestinal Adverse Reactions [see Warnings and Precautions (5.11, 5.12)] Seizures [see Warnings and Precautions (5.13)] Withdrawal [see Warnings and Precautions (5.14)] Most common adverse reactions (incidence >5%) were constipation, nausea, somnolence, dizziness, vomiting, pruritus, headache, dry mouth, asthenia, and sweating. (6.1) To report Suspected Adverse Reactions, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Adult Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of OXYCODONE HCl EXTENDED-RELEASE TABLETS 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 OXYCODONE HCl EXTENDED-RELEASE TABLETS in total daily doses ranging from 20 mg to 640 mg per day. The average total daily dose was approximately 105 mg per day. OXYCODONE HCl EXTENDED-RELEASE TABLETS may increase the risk of serious adverse reactions such as those observed with other opioid analgesics, including respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, or shock [see Overdosage (10) ] . The most common adverse reactions (>5%) reported by patients in clinical trials comparing OXYCODONE HCl EXTENDED-RELEASE TABLETS with placebo are shown in Table 2 below: TABLE 2: Common Adverse Reactions (>5%) Adverse Reaction OXYCODONE HCl EXTENDED-RELEASE TABLETS (n=227) Placebo (n=45) (%) (%) Constipation (23) (7) Nausea (23) (11) Somnolence (23) (4) Dizziness (13) (9) Pruritus (13) (2) Vomiting (12) (7) Headache (7) (7) Dry Mouth (6) (2) Asthenia (6) - Sweating (5) (2) In clinical trials, the following adverse reactions were reported in patients treated with OXYCODONE HCl EXTENDED-RELEASE TABLETS with an incidence between 1% and 5%: Gastrointestinal disorders: abdominal pain, diarrhea, dyspepsia, gastritis General disorders and administration site conditions: chills, fever Metabolism and nutrition disorders: anorexia Musculoskeletal and connective tissue disorders: twitching Psychiatric disorders: abnormal dreams, anxiety, confusion, dysphoria, euphoria, insomnia, nervousness, thought abnormalities Respiratory, thoracic and mediastinal disorders: dyspnea, hiccups Skin and subcutaneous tissue disorders: rash Vascular disorders: postural hypotension The following adverse reactions occurred in less than 1% of patientsinvolved in clinical trials: Blood and lymphatic system disorders: lymphadenopathy Ear and labyrinth disorders: tinnitus Eye disorders: abnormal vision Gastrointestinal disorders: dysphagia, eructation, flatulence, gastrointestinal disorder, increased appetite, stomatitis General disorders and administration site conditions: withdrawal syndrome (with and without seizures), edema, peripheral edema, thirst, malaise, chest pain, facial edema Injury, poisoning and procedural complications: accidental injury Investigations: ST depression Metabolism and nutrition disorders: dehydration Nervous system disorders: syncope, migraine, abnormal gait, amnesia, hyperkinesia, hypoesthesia, hypotonia, paresthesia, speech disorder, stupor, tremor, vertigo, taste...

Drug Interactions

7 DRUG INTERACTIONS Table 4 includes clinically significant drug interactions with OXYCODONE HCl EXTENDED-RELEASE TABLETS. Table 4: Clinically Significant Drug Interactions with OXYCODONE HCl EXTENDED-RELEASE TABLETS Inhibitors of CYP3A4 and CYP2D6 Clinical Impact: The concomitant use of OXYCODONE HCl EXTENDED-RELEASE TABLETS and CYP3A4 inhibitors can increase the plasma concentration of oxycodone, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of OXYCODONE HCl EXTENDED-RELEASE TABLETS and CYP2D6 and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of OXYCODONE HCl EXTENDED-RELEASE TABLETS is achieved [see Warnings and Precautions (5.5)] . After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the oxycodone plasma concentration will decrease [see Clinical Pharmacology (12.3)] , resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to oxycodone. Intervention: If concomitant use is necessary, consider dosage reduction of OXYCODONE HCl EXTENDED-RELEASE TABLETS until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the OXYCODONE HCl EXTENDED-RELEASE TABLETS dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Examples: Macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), protease inhibitors (e.g., ritonavir) CYP3A4 Inducers Clinical Impact: The concomitant use of OXYCODONE HCl EXTENDED-RELEASE TABLETS and CYP3A4 inducers can decrease the plasma concentration of oxycodone [see Clinical Pharmacology (12.3)] , resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to oxycodone [see Warnings and Precautions (5.5)] . After stopping a CYP3A4 inducer, as the effects of the inducer decline, the oxycodone plasma concentration will increase [see Clinical Pharmacology (12.3)] , which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression. Intervention: If concomitant use is necessary, consider increasing the OXYCODONE HCl EXTENDED-RELEASE TABLETS dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider OXYCODONE HCl EXTENDED-RELEASE TABLETS dosage reduction and monitor for signs of respiratory depression. Examples: Rifampin, carbamazepine, phenytoin Benzodiazepines and Other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Intervention: Reserve concomitant prescribing of...

Contraindications

4 CONTRAINDICATIONS OXYCODONE HCl EXTENDED-RELEASE TABLETS are contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions (5.3) ] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.7) ] Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.12) ] Hypersensitivity (e.g., anaphylaxis) to oxycodone [see Adverse Reactions (6.2) ] Significant respiratory depression (4) Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment (4) Known or suspected gastrointestinal obstruction, including paralytic ileus (4) Hypersensitivity to oxycodone (4)

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.4) ] . There are no available data with OXYCODONE HCl EXTENDED-RELEASE TABLETS in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, there was no embryo-fetal toxicity when oxycodone hydrochloride was orally administered to rats and rabbits, during the period of organogenesis, at doses 1.3 to 40 times the adult human dose of 60 mg/day, respectively. In a pre- and postnatal toxicity study, when oxycodone was orally administered to rats, there was transiently decreased pup body weight during lactation and the early post-weaning period at the dose equivalent to an adult dose of 60 mg/day. In several published studies, treatment of pregnant rats with oxycodone hydrochloride at clinically relevant doses and below resulted in neurobehavioral effects in offspring [see Data]. Based on animal data, advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid...

8.3 Females and Males of Reproductive Potential Infertility Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Adverse Reactions (6.2) , Clinical Pharmacology (12.2) ] .

Overdosage

10 OVERDOSAGE Clinical Presentation Acute overdose with OXYCODONE HCl EXTENDED-RELEASE TABLETS can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations. Treatment of Overdose In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen, vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life support techniques. Opioid antagonists, such as naloxone, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to opioid overdose, administer an opioid antagonist. Because the duration of reversal is expected to be less than the duration of action of oxycodone in oxycodone HCl extended-release tablets, carefully monitor the patient until spontaneous respiration is reliably reestablished. OXYCODONE HCl EXTENDED-RELEASE TABLETS will continue to release oxycodone and add to the oxycodone load for 24 to 48 hours or longer following ingestion, necessitating prolonged monitoring. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information. In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered....

How Supplied

16 HOW SUPPLIED OXYCODONE HCl EXTENDED-RELEASE TABLETS 10 mg are film-coated, round, white-colored, bi-convex tablets debossed with OP on one side and 10 on the other and are supplied as child-resistant closure, opaque plastic bottles of 100 (NDC 69238-2294-1). OXYCODONE HCl EXTENDED-RELEASE TABLETS 20 mg are film-coated, round, pink-colored, bi-convex tablets debossed with OP on one side and 20 on the other and are supplied as child-resistant closure, opaque plastic bottles of 100 (NDC 69238-2296-1) OXYCODONE HCl EXTENDED-RELEASE TABLETS 40 mg are film-coated, round, yellow-colored, bi-convex tablets debossed with OP on one side and 40 on the other and are supplied as child-resistant closure, opaque plastic bottles of 100 (NDC 69238-2298-1) OXYCODONE HCl EXTENDED-RELEASE TABLETS 80 mg are film-coated, round, green-colored, bi-convex tablets debossed with OP on one side and 80 on the other and are supplied as child-resistant closure, opaque plastic bottles of 100 (NDC 69238-2300-1) Store at 25°C (77°F); excursions permitted between 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. Store OXYCODONE HCl EXTENDED-RELEASE TABLETS securely and dispose of properly [see Patient Counseling Information (17) ] . Dispense in tight, light-resistant container.