DailyMed Label: Oxycodone HCl

DailyMed Label: Oxycodone HCl

2021

DailyMed Prescription

Oxycodone HCl

Oxycodone HCl

Amneal Pharmaceuticals NY LLC

NDC: 69238-2294

NDC: 69238-2296

NDC: 69238-2298

NDC: 69238-2300

NDC: 69238-2294

NDC: 69238-2294

NDC: 69238-2296

NDC: 69238-2296

NDC: 69238-2298

NDC: 69238-2298

NDC: 69238-2300

NDC: 69238-2300

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.

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.

Extended-release tablets: 10 mg, 20 mg, 40 mg, and 80 m g. 10 mg film-coated extended-release tablets (round, white-colored, bi-convex tablets debossed with OP on one side and 10 on the other) 20 mg film-coated extended-release tablets (round, pink-colored, bi-convex tablets debossed with OP on one side and 20 on the other) 40 mg film-coated extended-release tablets (round, yellow-colored, bi-convex tablets debossed with OP on one side and 40 on the other) 80 mg film-coated extended-release tablets (round, green-colored, bi-convex tablets debossed with OP on one side and 80 on the other)

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) ]

The following serious adverse reactions are described elsewhere in the labeling:

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 these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation. If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2, 2.7), Warnings and Precautions (5.1, 5.3, 5.6)] . Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol. Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome . Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue OXYCODONE HCl EXTENDED-RELEASE TABLETS if serotonin syndrome is suspected. Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue). Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions (5.3)]. Intervention: The use of OXYCODONE HCl EXTENDED-RELEASE TABLETS are not recommended for patients taking MAOIs or within 14 days of stopping such treatment. Examples: phenelzine, tranylcypromine, linezolid Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of OXYCODONE HCl EXTENDED-RELEASE TABLETS and/or precipitate withdrawal symptoms. Intervention: Avoid concomitant use. Examples: butorphanol, nalbuphine, pentazocine, buprenorphine Muscle Relaxants Clinical Impact: Oxycodone may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Intervention: Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of OXYCODONE HCl EXTENDED-RELEASE TABLETS and/or the muscle relaxant as necessary. Due to the risk of respiratory depression with concomitant use of skeletal muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose [see Dosage and Administration (2.2), Warnings and Precautions (5.3, 5.6)]. Examples: Cyclobenzaprine, metaxalone Diuretics Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Intervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Intervention: Monitor patients for signs of urinary retention or reduced gastric motility when OXYCODONE HCl EXTENDED-RELEASE TABLETS are used concomitantly with anticholinergic drugs.

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.

Oxycodone is a full opioid agonist and is relatively selective for the mu receptor, although it can bind to other opioid receptors at higher doses. The principal therapeutic action of oxycodone is analgesia. Like all full opioid agonists, there is no ceiling effect to analgesia for oxycodone. Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression. 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 are thought to play a role in the analgesic effects of this drug.

Carcinogenesis Carcinogenic potential of oxycodone was evaluated in a 2-year oral gavage study in Sprague- Dawley rats. Oxycodone did not increase the incidence of tumors in male and female rats at doses up to 6 mg/kg/day (approximately 0.1 times and 0.5 times for males and females, respectively, a human oxycodone dose of 60 mg/day based on AUC comparison).   Mutagenesis Oxycodone was genotoxic in the in vitro mouse lymphoma assay.  Oxycodone was negative when tested at appropriate concentrations in the in vitro chromosomal aberration assay, the in vitro bacterial reverse mutation assay (Ames test), and the in vivo bone marrow micronucleus assay in mice. Impairment of Fertility In a study of reproductive performance, rats were administered a once daily gavage dose of the vehicle or oxycodone hydrochloride (0.5, 2, and 8 mg/kg/day).  Male rats were dosed for 28 days before cohabitation with females, during the cohabitation and until necropsy (2-3 weeks post-cohabitation).  Females were dosed for 14 days before cohabitation with males, during cohabitation and up to Gestation Day 6.  Oxycodone hydrochloride did not affect reproductive function in male or female rats at any dose tested (up to 8 mg/kg/day), up to 1.3 times a human dose of 60 mg/day.

Adult Clinical Study A double-blind, placebo-controlled, fixed-dose, parallel group, two-week study was conducted in 133 patients with persistent, moderate to severe pain, who were judged as having inadequate pain control with their current therapy.  In this study, OXYCODONE HCl EXTENDED-RELEASE TABLETS 20 mg, but not 10 mg, was statistically significant in pain reduction compared with placebo. Pediatric Clinical Study OXYCODONE HCl EXTENDED-RELEASE TABLETS has been evaluated in an open-label clinical trial of 155 opioid-tolerant pediatric patients with moderate to severe chronic pain.  The mean duration of therapy was 20.7 days (range 1 to 43 days). The starting total daily doses ranged from 20 mg to 100 mg based on the patient’s prior opioid dose. The mean daily dose was 33.30 mg (range 20 to 140 mg/day).  In an extension study, 23 of the 155 patients were treated beyond four weeks, including 13 for 28 weeks.  Too few patients less than 11 years were enrolled in the clinical trial to provide meaningful safety data in this age group.