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| Product NDC Code | 0904-6966 | ||||
|---|---|---|---|---|---|
| Drug Name | Oxycodone hydrochloride |
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| Type | Brand | ||||
| Pharm Class | Full Opioid Agonists [MoA], Opioid Agonist [EPC] |
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| Active Ingredients |
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| Route | ORAL | ||||
| Dosage Form | TABLET | ||||
| RxCUI drug identifier | 1049611, 1049621 |
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| Application Number | ANDA203638 | ||||
| Labeler Name | Major Pharmaceuticals | ||||
| Packages |
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| Check if available Online | Get Medication Prices online with Discount |
Drug abuse and dependence
Information about whether the drug is a controlled substance, the types of abuse that can occur with the drug, and adverse reactions pertinent to those types of abuse.9 DRUG ABUSE AND DEPENDENCE 9.1 Controlled Substance Oxycodone HCl tablets contains oxycodone, a Schedule II controlled substance. 9.2 Abuse Oxycodone HCl tablets contains oxycodone, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see WARNINGS AND PRECAUTIONS (5.1) ] . Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Misuse and abuse of oxycodone HCl increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. The risk is increased with concurrent abuse of oxycodone HCl with alcohol and/or other CNS depressants. Abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of addiction. All patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Patients at high risk of oxycodone HCl abuse include those with a history of prolonged use of any opioid, including products containing oxycodone, those with a history of drug or alcohol abuse, or those who use oxycodone HCl in combination with other abused drugs. “Drug-seeking” behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated “loss” of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating healthcare provider(s). “Doctor shopping” (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control. Oxycodone HCl, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal 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 limit abuse of opioid drugs. Risks Specific to Abuse of Oxycodone HCl Abuse of oxycodone HCl poses a risk of overdose and death. The risk is increased with concurrent use of oxycodone HCl with alcohol and/or other CNS depressants. Oxycodone HCl is approved for oral use only. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV. 9.3 Dependence Both tolerance and physical dependence can develop during use of opioid therapy. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). Physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use. Do not abruptly discontinue oxycodone HCl in a patient physically dependent on opioids. Rapid tapering of oxycodone HCl in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. When discontinuing oxycodone HCl, gradually taper the dosage using a patient-specific plan that considers the following: the dose of oxycodone HCl the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for an extended period of time at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see DOSAGE AND ADMINISTRATION (2.4) , and WARNINGS AND PRECAUTIONS (5.14) ] . Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see USE IN SPECIFIC POPULATIONS (8.1) ] .
Overdosage of Oxycodone Hydrochloride
Information about signs, symptoms, and laboratory findings of acute ovedosage and the general principles of overdose treatment.10 OVERDOSAGE Clinical Presentation Acute overdose with oxycodone 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, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see CLINICAL PHARMACOLOGY (12.2) ] . Treatment of Overdose In case of overdose, priorities are the re-establishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support measures. 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 opioid reversal is expected to be less than the duration of action of oxycodone in oxycodone HCl tablets, carefully monitor the patient until spontaneous respiration is reliably reestablished. 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. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be initiated with care and by titration with smaller than usual doses of the antagonist.
Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.6 ADVERSE REACTIONS The following serious adverse reactions are described, or described in greater detail, in other sections: • Addiction, Abuse, and Misuse [see WARNINGS AND PRECAUTIONS (5.1) ] • Life-Threatening Respiratory Depression [see WARNINGS AND PRECAUTIONS (5.2) ] • Interactions with Benzodiazepines or Other CNS Depressants [see WARNINGS AND PRECAUTIONS (5.3) ] • Neonatal Opioid Withdrawal Syndrome [see WARNINGS AND PRECAUTIONS (5.4) ] • Opioid-Induce Hyperalgesia and Allodynia [see WARNINGS AND PRECAUTIONS (5.7) ] • Adrenal Insufficiency [see WARNINGS AND PRECAUTIONS (5.9) ] • Severe Hypotension [see WARNINGS AND PRECAUTIONS (5.10) ] • Gastrointestinal Adverse Reactions [see WARNINGS AND PRECAUTIONS (5.12) ] • Seizures [see WARNINGS AND PRECAUTIONS (5.13) ] • Withdrawal [see WARNINGS AND PRECAUTIONS (5.14) ] Most common adverse reactions (≥3%) were nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence. ( 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 Trials 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. Oxycodone HCl tablets have been evaluated in open label clinical trials in patients with cancer and nonmalignant pain. Oxycodone HCl tablets are associated with adverse experiences similar to those seen with other opioids. Serious adverse reactions associated with oxycodone HCl use included: respiratory depression, respiratory arrest, circulatory depression, cardiac arrest, hypotension, and/or shock. The common adverse reactions seen on initiation of therapy with oxycodone HCl are dose related and are typical opioid-related adverse reactions. The most frequent of these included nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence. The frequency of these reactions depended on several factors, including clinical setting, the patient’s level of opioid tolerance, and host factors specific to the individual. In all patients for whom dosing information was available (n=191) from the open-label and double-blind studies involving oxycodone HCl, the following adverse events were recorded in oxycodone HCl treated patients with an incidence ≥ 3%. In descending order of frequency they were: nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence. Other less frequently observed adverse reactions from opioid analgesics, including oxycodone HCl included: Blood and lymphatic system disorders: anemia, leukopenia Cardiac disorders: cardiac failure, palpitation, tachycardia Gastrointestinal disorders: abdominal pain, dry mouth, diarrhea, dyspepsia, dysphagia, glossitis, nausea, vomiting General disorders and administration site conditions: chills, edema, edema peripheral, pain, pyrexia Immune system disorders: hypersensitivity Infections and infestations: bronchitis, gingivitis, infection, pharyngitis, rhinitis, sepsis, sinusitis, urinary tract infection Injury, poisoning and procedural complications: injury Metabolism and nutrition disorders: decreased appetite, gout, hyperglycemia Musculoskeletal and connective tissue disorders: arthralgia, arthritis, back pain, bone pain, myalgia, neck pain, pathological fracture Nervous system disorders: hypertonia, hypoesthesia, migraine, neuralgia, tremor, vasodilation Psychiatric disorders: agitation, anxiety, confusional state, nervousness, personality disorder Respiratory, thoracic and mediastinal disorders: cough, dyspnea, epistaxis, laryngospasm, lung disorder Skin and subcutaneous tissue disorders: photosensitivity reaction, rash, hyperhidrosis, urticaria Vascular disorders: thrombophlebitis, hemorrhage, hypotension, vasodilatation 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of oxycodone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. General disorders and administrative site disorders: drug withdrawal syndrome neonatal [see WARNINGS AND PRECAUTIONS (5.4) ] Respiratory, thoracic and mediastinal disorders: pharyngeal edema Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs [see DRUG INTERACTIONS (7) ] . Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use [see WARNINGS AND PRECAUTIONS (5.9) ] . Anaphylaxis: Anaphylactic reaction has been reported with ingredients contained in oxycodone HCl tablets [see CONTRAINDICATIONS (4) ] . Androgen deficiency: Cases of androgen deficiency have occurred with use of opioids for an extended period of time [see CLINICAL PHARMACOLOGY (12.2) ] . Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see WARNINGS AND PRECAUTIONS (5.7) ] . Hypoglycemia: Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g., diabetes).
Oxycodone Hydrochloride Drug Interactions
Information about and practical guidance on preventing clinically significant drug/drug and drug/food interactions that may occur in people taking the drug.7 DRUG INTERACTIONS Table 1 includes clinically significant drug interactions with oxycodone HCl. Table 1: Clinically Significant Drug Interactions with Oxycodone HCl Inhibitors of CYP3A4 and CYP2D6 Clinical Impact: The concomitant use of oxycodone HCl 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 and CYP2D6 and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of oxycodone HCl is achieved [see WARNINGS AND PRECAUTIONS (5.3) ] . 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 until stable drug effects are achieved. Evaluate patients at frequent intervals for respiratory depression and sedation. If a CYP3A4 inhibitor is discontinued, consider increasing the oxycodone HCl dosage until stable drug effects are achieved. Evaluate 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 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 (5.6) ] . 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 dosage until stable drug effects are achieved. Evaluate patients for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider oxycodone HCl dosage reduction and evaluate patients at frequent intervals for signs of respiratory depression and sedation. 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 [see WARNINGS AND PRECAUTIONS (5.3) ] . 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. Inform patients and caregivers of this potential interaction and educate them on the signs and symptoms of respiratory depression (including sedation). If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see DOSAGE AND ADMINISTRATION (2.2) , WARNINGS AND PRECAUTIONS (5.1 , 5.2 , 5.3) ] . 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 [see ADVERSE REACTIONS (6.2) ] . Intervention: If concomitant use is warranted, frequently evaluate the patient, particularly during treatment initiation and dose adjustment. Discontinue oxycodone HCl 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 (5.2) ] . Intervention: The use of oxycodone HCl is not recommended for patients taking MAOIs or within 14 days of stopping such treatment. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. Examples: phenelzine, tranylcypromine, linezolid Mixed Agonist/Antagonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of oxycodone HCl and/or may 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: Because respiratory depression may be greater than otherwise expected, decrease the dosage of oxycodone HCl 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 (5.2 , 5.3) ] . Diuretics Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Intervention: Evaluate patients for signs of dismissed diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. Anticholinergic Drugs Clinical Impact: The concomitant risk of anticholinergic drugs may result in increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Intervention: Evaluate patients for signs of urinary retention or reduced gastric motility when oxycodone HCl is used concurrently with anticholinergic drugs. • Serotonergic Drugs: Concomitant use may result in serotonin syndrome. Discontinue oxycodone HCl tablets if serotonin syndrome is suspected. ( 7 ) • Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics: Avoid use with oxycodone HCl tablets because they may reduce analgesic effect of oxycodone HCl tablets or precipitate withdrawal symptoms. ( 7 ) • Monoamine Oxidase Inhibitors (MAOIs): Can potentiate the effects of morphine. Avoid concomitant use in patients receiving MAOIs or within 14 days of stopping treatment with an MAOI. ( 7 )
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Oxycodone is a full opioid agonist and is relatively selective for the mu-opioid 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 for analgesia with 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. 12.2 Pharmacodynamics Effects on Central Nervous System Oxycodone produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation. 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 origins may produce similar findings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations. Effects on 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 biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase. Effects on Cardiovascular System Oxycodone produces peripheral vasodilatation, which may result in orthostatic hypotension or syncope. Manifestations of histamine release and/or peripheral vasodilatation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension. Effects on the Endocrine System Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see ADVERSE REACTIONS (6.2) ] . They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon. Use of opioids for an extended period of time may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date [see ADVERSE REACTIONS (6.2) ] . Effects on the Immune System Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown. Overall, the effects of opioids appear to be modestly immunosuppressive. Concentration–Efficacy Relationships The minimum effective analgesic concentration will vary widely among patients, especially among patients who have been previously treated with opioid agonists. 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 [see DOSAGE AND ADMINISTRATION (2.1, 2.3) ] . Concentration–Adverse Reaction Relationships There is a relationship between increasing oxycodone plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression. In opioid-tolerant patients, the situation may be altered by the development of tolerance to opioid-related adverse reactions [see DOSAGE AND ADMINISTRATION (2.1 , 2.3) ] . 12.3 Pharmacokinetics The activity of oxycodone HCl tablets is primarily due to the parent drug oxycodone. Oxycodone HCl tablets are designed to provide immediate release of oxycodone. Table 2: Pharmacokinetic Parameters (Mean±SD) Dose\Parameters AUC (ngxhr/mL) C max (ng/mL) T max (hr) C min (ng/mL) C avg (ng/mL) Half-Life (hr) Single Dose Pharmacokinetics Oxycodone HCl 5 mg tabs x 3 133.2±33 22.3±8.2 1.8±1.8 n/a n/a 3.73±0.9 Oxycodone HCl 15 mg tab 128.2±35.1 22.2±7.6 1.4±0.7 n/a n/a 3.55±1.0 Oxycodone HCl Liquid Concentrate 15 mg oral solution 130.6±34.7 21.1±6.1 1.9±1.5 n/a n/a 3.71±0.8 Oxycodone HCl 30 mg tab 268.2±60.7 39.3±14.0 2.6±3.0 n/a n/a 3.85±1.3 Food-Effect, Single Dose Oxycodone HCl 10 mg/10 mL oral sol’n (fasted) 105±6.2 19.0±3.7 1.25±0.5 n/a n/a 2.9±0.4 Oxycodone HCl 10 mg/10 mL oral sol’n (fed) 133±25.2 17.7±3.0 2.54±1.2 n/a n/a 3.3±0.5 Multiple-Dose Studies AUC (72 to 84) Oxycodone HCl 5 mg tabs q6h x 14 doses 113.3±24.0 15.7±3.2 1.3±0.3 7.4±1.8 9.4±2.0 n/a Oxycodone HCl 3.33 mg (3.33 mL) oral sol’n. q4h x 21 doses 99.0±24.8 12.9±3.1 1.0±0.3 7.2±2.3 9.7±2.6 n/a Absorption About 60% to 87% of an oral dose of oxycodone reaches the systemic circulation in comparison to a parenteral dose. This high oral bioavailability (compared to other oral opioids) is due to lower presystemic and/or first-pass metabolism of oxycodone. The relative oral bioavailability of oxycodone HCl 15 mg and 30 mg tablets, compared to the 5 mg oxycodone HCl tablets, is 96% and 101% respectively. Oxycodone HCl 15 mg tablets and 30 mg tablets are bioequivalent to the 5 mg oxycodone HCl tablet (see Table 2 for pharmacokinetic parameters). Dose proportionality of oxycodone has been established using the oxycodone HCl 5 mg tablets at doses of 5 mg, 15 mg (three 5 mg tablets) and 30 mg (six 5 mg tablets) based on extent of absorption (AUC) (see Figure 1). It takes approximately 18 to 24 hours to reach steady-state plasma concentrations of oxycodone with oxycodone HCl tablets. Food Effect A single-dose food effect study was conducted in normal volunteers using the 5 mg/5 mL solution. The concurrent intake of a high fat meal was shown to enhance the extent (27% increase in AUC), but not the rate of oxycodone absorption from the oral solution (see Table 2). In addition, food caused a delay in T max (1.25 to 2.54 hour). Similar effects of food are expected with the 15 mg and 30 mg tablets. Distribution Following intravenous administration, the volume of distribution (Vss) for oxycodone was 2.6 L/kg. Plasma protein binding of oxycodone at 37°C and a pH of 7.4 was about 45%. Oxycodone has been found in breast milk [see SPECIAL POPULATIONS (8.2) ] . Elimination Metabolism A high portion of oxycodone is N-dealkylated to noroxycodone during first-pass metabolism, and is catalyzed by CYP3A4. Oxymorphone is formed by the O-demethylation of oxycodone. The metabolism of oxycodone to oxymorphone is catalyzed by CYP2D6 [see DRUG INTERACTIONS (7) ] . Free and conjugated noroxycodone, free and conjugated oxycodone, and oxymorphone are excreted in human urine following a single oral dose of oxycodone. The major circulating metabolite is noroxycodone with an AUC ratio of 0.6 relative to that of oxycodone. Oxymorphone is present in the plasma only in low concentrations. The analgesic activity profile of other metabolites is not known at present. 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. Apparent elimination half-life of oxycodone following the administration of oxycodone HCl was 3.5 to 4 hours. Specific Populations Age: Geriatric Population Population pharmacokinetic studies conducted with oxycodone HCl, indicated that the plasma concentrations of oxycodone did not appear to be increased in patients over the age of 65. Hepatic Impairment In a clinical trial supporting the development of oxycodone HCl, too few patients with decreased hepatic function were evaluated to study these potential differences. However, because oxycodone is extensively metabolized in the liver, its clearance may decrease in hepatic impaired patients [see USE IN SPECIFIC POPULATIONS (8.6) ] . Renal Impairment This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function [see USE IN SPECIFIC POPULATIONS (8.7) ] . figure 1
Mechanism of action
Information about the established mechanism(s) of the drugÕs action in humans at various levels (for example receptor, membrane, tissue, organ, whole body). If the mechanism of action is not known, this field contains a statement about the lack of information.12.1 Mechanism of Action Oxycodone is a full opioid agonist and is relatively selective for the mu-opioid 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 for analgesia with 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.
Pharmacodynamics
Information about any biochemical or physiologic pharmacologic effects of the drug or active metabolites related to the drugÕs clinical effect in preventing, diagnosing, mitigating, curing, or treating disease, or those related to adverse effects or toxicity.12.2 Pharmacodynamics Effects on Central Nervous System Oxycodone produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation. 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 origins may produce similar findings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations. Effects on 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 biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase. Effects on Cardiovascular System Oxycodone produces peripheral vasodilatation, which may result in orthostatic hypotension or syncope. Manifestations of histamine release and/or peripheral vasodilatation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension. Effects on the Endocrine System Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see ADVERSE REACTIONS (6.2) ] . They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon. Use of opioids for an extended period of time may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the clinical syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date [see ADVERSE REACTIONS (6.2) ] . Effects on the Immune System Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown. Overall, the effects of opioids appear to be modestly immunosuppressive. Concentration–Efficacy Relationships The minimum effective analgesic concentration will vary widely among patients, especially among patients who have been previously treated with opioid agonists. 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 [see DOSAGE AND ADMINISTRATION (2.1, 2.3) ] . Concentration–Adverse Reaction Relationships There is a relationship between increasing oxycodone plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression. In opioid-tolerant patients, the situation may be altered by the development of tolerance to opioid-related adverse reactions [see DOSAGE AND ADMINISTRATION (2.1 , 2.3) ] .
Pharmacokinetics
Information about the clinically significant pharmacokinetics of a drug or active metabolites, for instance pertinent absorption, distribution, metabolism, and excretion parameters.12.3 Pharmacokinetics The activity of oxycodone HCl tablets is primarily due to the parent drug oxycodone. Oxycodone HCl tablets are designed to provide immediate release of oxycodone. Table 2: Pharmacokinetic Parameters (Mean±SD) Dose\Parameters AUC (ngxhr/mL) C max (ng/mL) T max (hr) C min (ng/mL) C avg (ng/mL) Half-Life (hr) Single Dose Pharmacokinetics Oxycodone HCl 5 mg tabs x 3 133.2±33 22.3±8.2 1.8±1.8 n/a n/a 3.73±0.9 Oxycodone HCl 15 mg tab 128.2±35.1 22.2±7.6 1.4±0.7 n/a n/a 3.55±1.0 Oxycodone HCl Liquid Concentrate 15 mg oral solution 130.6±34.7 21.1±6.1 1.9±1.5 n/a n/a 3.71±0.8 Oxycodone HCl 30 mg tab 268.2±60.7 39.3±14.0 2.6±3.0 n/a n/a 3.85±1.3 Food-Effect, Single Dose Oxycodone HCl 10 mg/10 mL oral sol’n (fasted) 105±6.2 19.0±3.7 1.25±0.5 n/a n/a 2.9±0.4 Oxycodone HCl 10 mg/10 mL oral sol’n (fed) 133±25.2 17.7±3.0 2.54±1.2 n/a n/a 3.3±0.5 Multiple-Dose Studies AUC (72 to 84) Oxycodone HCl 5 mg tabs q6h x 14 doses 113.3±24.0 15.7±3.2 1.3±0.3 7.4±1.8 9.4±2.0 n/a Oxycodone HCl 3.33 mg (3.33 mL) oral sol’n. q4h x 21 doses 99.0±24.8 12.9±3.1 1.0±0.3 7.2±2.3 9.7±2.6 n/a Absorption About 60% to 87% of an oral dose of oxycodone reaches the systemic circulation in comparison to a parenteral dose. This high oral bioavailability (compared to other oral opioids) is due to lower presystemic and/or first-pass metabolism of oxycodone. The relative oral bioavailability of oxycodone HCl 15 mg and 30 mg tablets, compared to the 5 mg oxycodone HCl tablets, is 96% and 101% respectively. Oxycodone HCl 15 mg tablets and 30 mg tablets are bioequivalent to the 5 mg oxycodone HCl tablet (see Table 2 for pharmacokinetic parameters). Dose proportionality of oxycodone has been established using the oxycodone HCl 5 mg tablets at doses of 5 mg, 15 mg (three 5 mg tablets) and 30 mg (six 5 mg tablets) based on extent of absorption (AUC) (see Figure 1). It takes approximately 18 to 24 hours to reach steady-state plasma concentrations of oxycodone with oxycodone HCl tablets. Food Effect A single-dose food effect study was conducted in normal volunteers using the 5 mg/5 mL solution. The concurrent intake of a high fat meal was shown to enhance the extent (27% increase in AUC), but not the rate of oxycodone absorption from the oral solution (see Table 2). In addition, food caused a delay in T max (1.25 to 2.54 hour). Similar effects of food are expected with the 15 mg and 30 mg tablets. Distribution Following intravenous administration, the volume of distribution (Vss) for oxycodone was 2.6 L/kg. Plasma protein binding of oxycodone at 37°C and a pH of 7.4 was about 45%. Oxycodone has been found in breast milk [see SPECIAL POPULATIONS (8.2) ] . Elimination Metabolism A high portion of oxycodone is N-dealkylated to noroxycodone during first-pass metabolism, and is catalyzed by CYP3A4. Oxymorphone is formed by the O-demethylation of oxycodone. The metabolism of oxycodone to oxymorphone is catalyzed by CYP2D6 [see DRUG INTERACTIONS (7) ] . Free and conjugated noroxycodone, free and conjugated oxycodone, and oxymorphone are excreted in human urine following a single oral dose of oxycodone. The major circulating metabolite is noroxycodone with an AUC ratio of 0.6 relative to that of oxycodone. Oxymorphone is present in the plasma only in low concentrations. The analgesic activity profile of other metabolites is not known at present. 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. Apparent elimination half-life of oxycodone following the administration of oxycodone HCl was 3.5 to 4 hours. Specific Populations Age: Geriatric Population Population pharmacokinetic studies conducted with oxycodone HCl, indicated that the plasma concentrations of oxycodone did not appear to be increased in patients over the age of 65. Hepatic Impairment In a clinical trial supporting the development of oxycodone HCl, too few patients with decreased hepatic function were evaluated to study these potential differences. However, because oxycodone is extensively metabolized in the liver, its clearance may decrease in hepatic impaired patients [see USE IN SPECIFIC POPULATIONS (8.6) ] . Renal Impairment This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function [see USE IN SPECIFIC POPULATIONS (8.7) ] . figure 1
Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.4 CONTRAINDICATIONS Oxycodone HCl is contraindicated in patients with: • Significant respiratory depression [see WARNINGS AND PRECAUTIONS (5.2) ]. • Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment or hypercarbia [see WARNINGS AND PRECAUTIONS (5.8) ]. • Known or suspected gastrointestinal obstruction, including paralytic ileus [see WARNINGS AND PRECAUTIONS (5.12) ] . • Known 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 )
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.11 DESCRIPTION Oxycodone HCl tablets, USP contains oxycodone, an opioid agonist. Each tablet for oral administration contains 5 mg, 10 mg, 15 mg, 20 mg or 30 mg, of oxycodone hydrochloride, USP. Oxycodone hydrochloride, USP is a white, odorless crystalline powder derived from the opium alkaloid, thebaine. Oxycodone hydrochloride, USP dissolves in water (1 g in 6 to 7 mL) and is considered slightly soluble in alcohol (octanol water partition coefficient is 0.7). Chemically, oxycodone hydrochloride, USP is 4, 5α-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one hydrochloride and has the following structural formula: Each tablet also contains the following inactive ingredients: corn starch, lactose monohydrate, microcrystalline cellulose, sodium starch glycolate and stearic acid. The 10 mg tablet also contains D&C Red No. 27. The 15 mg tablet also contains the following inactive ingredients: D&C Yellow No. 10 and FD&C Blue No. 2. The 20 mg tablet also contains the following inactive ingredients: FD&C Blue No. 2, FD&C Red No. 40 and FD&C Yellow No. 6. The 30 mg tablet also contains the following inactive ingredients: D&C Yellow No. 10 and FD&C Blue No. 2. The 5 mg, 10 mg, 15 mg, 20 mg and 30 mg tablets contain the equivalent of 4.6 mg, 9 mg, 13.5 mg, 18 mg, and 27 mg, respectively, of oxycodone free base. formula
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.2 DOSAGE AND ADMINISTRATION • Oxycodone HCl tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. (2.1) • Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of oxycodone HCl tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. (2.1 , 5) • Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. (2.1) • Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying case and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse. (2.1 , 5.1) • Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with oxycodone HCl tablets. Consider this risk when selecting an initial dose and when making dose adjustments. (2.1 , 5.2) • 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 tablets. Consider prescribing naloxone based on the patient’s risk factors for overdose. (2.2 , 5.1 , 5.2 , 5.3) • Initiate treatment with oxycodone HCl tablets in a dosing range of 5 to 15 mg every 4 to 6 hours as needed for pain and at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient’s response to their initial dose of oxycodone HCl tablets. (2.3 , 2.4) • Do not abruptly discontinue oxycodone HCl in a physically dependent patient because rapid discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. (2.5) 2.1 Important Dosage and Administration Instructions • Oxycodone HCl tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. • Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see WARNINGS AND PRECAUTIONS (5) ] . Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of oxycodone HCl tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. • Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. • There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see WARNINGS AND PRECAUTIONS (5.1) ] . • Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with oxycodone HCl tablets. Consider this risk when selecting an initial dose and when making dose adjustments [see WARNINGS AND PRECAUTIONS (5) ] . 2.2 Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with oxycodone HCl tablets [see WARNINGS AND PRECAUTIONS (5.3) ] . Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program). Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient [see WARNINGS AND PRECAUTIONS (5.1 , 5.2 , 5.3) ] . Consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose . 2.3 Initial Dosage Although it is not possible to list every condition that is important to the selection of the initial dose of oxycodone HCl tablets, attention must be given to: 1. the daily dose, potency and characteristics of a full agonist or mixed agonist/antagonist the patient has been taking previously. 2. the reliability of the relative potency estimate to calculate the dose of oxycodone HCl needed. 3. the degree of opioid tolerance. 4. the general condition and medical status of the patient, including the patient’s weight and age. 5. the balance between pain management and adverse reactions. 6. the type and severity of the patient’s pain. 7. risk factors for abuse or addiction, including a prior history of abuse or addiction. Use of Oxycodone HCl Tablets as the First Opioid Analgesic Initiate treatment with oxycodone HCl tablets in a dosing range of 5 to 15 mg every 4 to 6 hours as needed for pain, and at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient’s response to their initial dose of oxycodone HCl tablets. Conversion from Other Opioids to Oxycodone HCl Tablets There is inter-patient variability in the potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dosage of oxycodone HCl tablets. It is safer to underestimate a patient’s 24-hour oxycodone HCl tablets dosage than to overestimate the 24-hour oxycodone HCl tablets dosage and manage an adverse reaction due to overdose. If a patient has been receiving opioid-containing medications prior to taking oxycodone HCl tablets, the potency of the prior opioid relative to oxycodone should be factored into the selection of the total daily dose (TDD) of oxycodone. In converting patients from other opioids to oxycodone HCl tablets close observation and adjustment of dosage based upon the patient’s response to oxycodone HCl tablets are imperative. Administration of supplemental analgesia for breakthrough or incident pain and titration of the total daily dose of oxycodone HCl tablets may be necessary, especially in patients who have disease states that are changing rapidly. Conversion from Fixed-Ratio Opioid/Acetaminophen, Opioid/Aspirin, or Opioid/Nonsteroidal Combination Drugs When converting patients from fixed ratio opioid/non-opioid drug regimens a decision should be made whether or not to continue the non-opioid analgesic. If a decision is made to discontinue the use of non-opioid analgesic, it may be necessary to titrate the dose of oxycodone HCl tablets in response to the level of analgesia and adverse effects afforded by the dosing regimen. If the non-opioid regimen is continued as a separate single entity agent, the starting dose oxycodone HCl tablets should be based upon the most recent dose of opioid as a baseline for further titration of oxycodone. Incremental increases should be gauged according to side effects to an acceptable level of analgesia. Conversion from Oxycodone HCl Immediate-Release Tablets to Extended-Release Oxycodone The relative bioavailability of oxycodone HCl immediate-release tablets compared to extended-release oxycodone is unknown, so conversion to extended-release oxycodone may lead to increased risk of excessive sedation and respiratory depression. 2.4 Titration and Maintenance of Therapy Individually titrate oxycodone HCl tablets to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving oxycodone HCl tablets to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions, as well as to reassess for the development of addiction, abuse, or misuse [see WARNINGS AND PRECAUTIONS (5.1 , 5.14) ] . Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the oxycodone HCl tablets dosage. If after increasing the dosage, unacceptable opioid-related adverse reactions are observed (including an increase in pain after a dosage increase), consider reducing the dosage [see WARNINGS AND PRECAUTIONS (5) ] . Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions. 2.5 Safe Reduction or Discontinuation of Oxycodone HCl Tablets Do not abruptly discontinue oxycodone HCl in patients who may be physically dependent on opioids. Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances. When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking oxycodone HCl, there are a variety of factors that should be considered, including the total daily dose of opioid (including oxycodone HCl tablets) the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with comorbid pain and substance use disorders may benefit from referral to a specialist. There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on oxycodone HCl who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper. It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms include 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. If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, evaluate patients for any changes in mood, emergence of suicidal thoughts, or use of other substances. When managing patients taking opioid analgesics, particularly those who have been treated for an extended period of time, and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic [see WARNINGS AND PRECAUTIONS (5.14) , DRUG ABUSE AND DEPENDENCE (9.3) ] .
Dosage forms and strengths
Information about all available dosage forms and strengths for the drug product to which the labeling applies. This field may contain descriptions of product appearance.3 DOSAGE FORMS AND STRENGTHS Oxycodone HCl tablets, USP are available in following strength: Oxycodone HCl tablets USP, 5 mg are supplied as white, round, biconvex tablets debossed with “A” on the left and “04” on the right of the score on one side and plain on the other side. Oxycodone HCl tablets USP, 10 mg are supplied as pink, round, biconvex tablets debossed with “A” on the left and “48” on the right of the score on one side and plain on the other side. Oxycodone HCl tablets USP, 15 mg are supplied as green, round, biconvex tablets debossed with “A” on the left and “49” on the right of the score on one side and plain on the other side. Oxycodone HCl tablets USP, 20 mg are supplied as gray, round, biconvex tablets debossed with “A” on the left and “50” on the right of the score on one side and plain on the other side. Oxycodone HCl tablets USP, 30 mg are supplied as blue, round, biconvex tablets debossed with “A” on the left and “51” on the right of the score on one side and plain on the other side. Immediate-release tablets: 5 mg, 10 mg, 15 mg, 20 mg, 30 mg ( 3 )
Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.1 INDICATIONS AND USAGE Oxycodone hydrochloride (HCl) tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration [see WARNINGS AND PRECAUTIONS (5.1) ] , reserve oxycodone HCl tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or opioid combination products): • Have not been tolerated or are not expected to be tolerated, • Have not provided adequate analgesia or are not expected to provide adequate analgesia. Oxycodone HCl tablets should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate. Oxycodone HCl tablets are an opioid agonist indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. (1) Limitations of Use: Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, reserve oxycodone HCl tablets for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or non-opioid combination products): • Have not been tolerated or are not expected to be tolerated, • Have not provided adequate analgesia or are not expected to provide adequate analgesia. Oxycodone HCl tablets should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.
Spl product data elements
Usually a list of ingredients in a drug product.Oxycodone Hydrochloride Oxycodone OXYCODONE HYDROCHLORIDE OXYCODONE STARCH, CORN LACTOSE MONOHYDRATE MICROCRYSTALLINE CELLULOSE SODIUM STARCH GLYCOLATE TYPE A POTATO STEARIC ACID A;04 Oxycodone Hydrochloride Oxycodone OXYCODONE HYDROCHLORIDE OXYCODONE STARCH, CORN LACTOSE MONOHYDRATE MICROCRYSTALLINE CELLULOSE SODIUM STARCH GLYCOLATE TYPE A POTATO STEARIC ACID D&C YELLOW NO. 10 FD&C BLUE NO. 2 A;49
Carcinogenesis and mutagenesis and impairment of fertility
Information about carcinogenic, mutagenic, or fertility impairment potential revealed by studies in animals. Information from human data about such potential is part of the warnings field.13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long-term studies have not been performed in animals to evaluate the carcinogenic potential of oxycodone HCl tablets or oxycodone. Mutagenesis Oxycodone hydrochloride was genotoxic in an in vitro mouse lymphoma assay in the presence of metabolic activation. There was no evidence of genotoxic potential in an in vitro bacterial reverse mutation assay ( Salmonella typhimurium and Escherichia coli ) or in an assay for chromosomal aberrations ( in vivo mouse bone marrow micronucleus assay). Impairment of Fertility Studies in animals to evaluate the potential impact of oxycodone on fertility have not been conducted.
Nonclinical toxicology
Information about toxicology in non-human subjects.13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long-term studies have not been performed in animals to evaluate the carcinogenic potential of oxycodone HCl tablets or oxycodone. Mutagenesis Oxycodone hydrochloride was genotoxic in an in vitro mouse lymphoma assay in the presence of metabolic activation. There was no evidence of genotoxic potential in an in vitro bacterial reverse mutation assay ( Salmonella typhimurium and Escherichia coli ) or in an assay for chromosomal aberrations ( in vivo mouse bone marrow micronucleus assay). Impairment of Fertility Studies in animals to evaluate the potential impact of oxycodone on fertility have not been conducted.
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.Package/Label Display Panel Oxycodone Hydrochloride Tablets, USP CII 5 mg 100 TABLETS (10 x 10) 5mg carton label
Package/Label Display Panel Oxycodone Hydrochloride Tablets, USP CII 15 mg 100 TABLETS (10 x 10) 15mg carton label
Recent major changes
A list of the section(s) that contain substantive changes that have been approved by FDA in the product labeling. The headings and subheadings, if appropriate, affected by the change are listed together with each section’s identifying number and the month and year on which the change was incorporated in the labeling.RECENT MAJOR CHANGES Boxed Warning 12/2023 Indications and Usage (1) 12/2023 Dosage and Administration (2.1 , 2.3 , 2.4) 12/2023 Warnings and Precautions (5.7) 12/2023
Oxycodone Hydrochloride: Information for patients
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Storage and Disposal Because of the risks associated with accidental ingestion, misuse, and abuse, advise patients to store oxycodone HCl securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Inform patients that leaving oxycodone HCl unsecured can pose a deadly risk to others in the home [see WARNINGS AND PRECAUTIONS (5.1 , 5.3) , DRUG ABUSE AND DEPENDENCE (9.2) ] . Advise patients and caregivers that when medicines are no longer needed, they should be disposed of promptly. Expired, unwanted, or unused oxycodone HCl should be disposed of by flushing the unused medication down the toilet if a drug take-back option is not readily available. Inform patients that they can visit www.fda.gov/drugdisposal for a complete list of medicines recommended for disposal by flushing, as well as additional information on disposal of unused medicines. Addiction, Abuse and Misuse Inform patients that the use of oxycodone HCl, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see WARNINGS AND PRECAUTIONS (5.1) ] . Instruct patients not to share oxycodone HCl with others and to take steps to protect oxycodone HCl from theft and misuse. Life-Threatening Respiratory Depression Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting oxycodone HCl or when the dosage is increased, and that it can occur even at recommended dosages. Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right away in the event of a known or suspected overdose [see WARNINGS AND PRECAUTIONS (5.2) , OVERDOSAGE (10) ] . Accidental Ingestion Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see WARNINGS AND PRECAUTIONS (5.2) ] . Interactions with Benzodiazepines and Other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur if oxycodone HCl is used with benzodiazepines or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a healthcare provider [see WARNINGS AND PRECAUTIONS (5.3) , DRUG INTERACTIONS (7) ] . Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose Discuss with the patient and caregiver the availability of naloxone for the emergency treatment of opioid overdose, both when initiating and renewing treatment with oxycodone HCl. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing requirements or guidelines (e.g., by prescription, directly from a pharmacist, or as part of a community-based program) [see DOSAGE AND ADMINISTRATION (2.2) , WARNINGS AND PRECAUTIONS (5.2) ] . Educate patients and caregivers on how to recognize the signs and symptoms of an overdose. Explain to patients and caregivers that naloxone’s effects are temporary, and that they must call 911 or get emergency medical help right away in all cases of known or suspected opioid overdose, even if naloxone is administered [see OVERDOSAGE (10) ] . If naloxone is prescribed, also advise patients and caregivers: • How to treat with naloxone in the event of an opioid overdose • To tell family and friends about their naloxone and to keep it in a place where family and friends can access it in an emergency • To read the Patient Information (or other educational material) that will come with their naloxone. Emphasize the importance of doing this before an opioid emergency happens, so the patient and caregiver will know what to do. Hyperalgesia and Allodynia Inform patients and caregivers not to increase opioid dosage without first consulting a clinician. Advise patients to seek medical attention if they experience symptoms of hyperalgesia, including worsening pain, increased sensitivity to pain, or new pain [see WARNINGS AND PRECAUTIONS (5.7) , ADVERSE REACTIONS (6.2) ] . Serotonin Syndrome Inform patients that opioids could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs. Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their healthcare providers if they are taking, or plan to take serotonergic medication [see DRUG INTERACTIONS (7) ] . MAOI Interaction Inform patients to avoid taking oxycodone HCl while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking oxycodone HCl [see DRUG INTERACTIONS (7) ] . Important Administration Instructions Instruct patients how to properly take oxycodone HCl. Patients should be advised not to adjust the dose of oxycodone HCl without consulting the prescribing healthcare provider [see DOSAGE AND ADMINISTRATION (2) ] . Important Discontinuation Instructions In order to avoid developing withdrawal symptoms, instruct patients not to discontinue oxycodone HCl without first discussing a tapering plan with the prescriber [see DOSAGE AND ADMINISTRATION (2.5) ] . Driving or Operating Machinery Inform patients that oxycodone HCl may impair the ability to perform potentially hazardous activities such as driving a car or operating dangerous machinery. Advise patients not to perform such tasks until they know how they will react to the medication [see WARNINGS AND PRECAUTIONS (5.15) ] . Constipation Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [see ADVERSE REACTIONS (6) , CLINICAL PHARMACOLOGY (12.1) ] . Adrenal Insufficiency Inform patients that opioids could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness and low blood pressure. Advise patients to seek medical attention if they experience a constellation of these symptoms [see WARNINGS AND PRECAUTIONS (5.9) ] . Hypotension Inform patients that oxycodone HCl may cause orthostatic hypotension and syncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from sitting or lying position) [see WARNINGS AND PRECAUTIONS (5.10) ] . Anaphylaxis Inform patients that anaphylaxis has been reported with ingredients contained in oxycodone HCl. Advise patients how to recognize such a reaction and when to seek medical attention [see CONTRAINDICATIONS (4) , ADVERSE REACTIONS (6.2) ] . Pregnancy Neonatal Opioid Withdrawal Syndrome Inform female patients of reproductive potential that use of oxycodone HCl for an extended period of time during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated [see WARNINGS AND PRECAUTIONS (5.4) , USE IN SPECIFIC POPULATIONS (8.1) ] . Embryo-Fetal Toxicity Inform female patients of reproductive potential that oxycodone HCl can cause fetal harm and to inform their healthcare provider of a known or suspected pregnancy [see USE IN SPECIFIC POPULATIONS (8.1) ] . Lactation Advise breastfeeding women using oxycodone HCl to carefully observe infants for increased sleepiness (more than usual), breathing difficulties, or limpness. Instruct breastfeeding women to seek immediate medical care if they notice these signs [see USE IN SPECIFIC POPULATIONS (8.2) ] . Infertility Inform patients that use of opioids for an extended period of time may cause reduced fertility. It is not known whether these effects on fertility are reversible [see USE IN SPECIFIC POPULATIONS (8.3) ] . Manufactured by: Amneal Pharmaceuticals of NY, LLC Brookhaven, NY 11719 Packaged and Distributed by: MAJOR® PHARMACEUTICALS Indianapolis, IN 46268 USA Refer to package label for Distributor's NDC Number Rev. 04-2024-09 Dispense with Medication Guide available at: documents.amneal.com/mg/oxycodone-hcl-tab.pdf
Spl medguide
Information about the patient medication guide that accompanies the drug product. Certain drugs must be dispensed with an accompanying medication guide. This field may contain information about when to consult the medication guide and the contents of the medication guide.Medication Guide Dispense with Medication Guide available at: documents.amneal.com/mg/oxycodone-hcl-tab.pdf Oxycodone (ox” i koe’ done) HCl Tablets USP, CII Oxycodone HCl tablets are: • A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage pain severe enough to require an opioid pain medicine, when other pain treatments such as non-opioid pain medicines do not treat your pain well enough or you cannot tolerate them. • An opioid pain medicine that can put you at risk for overdose and death. Even if you take your dose correctly as prescribed you are at risk for opioid addiction, abuse, and misuse that can lead to death. Important information about oxycodone HCl tablets: Get emergency help or call 911 right away if you take too much oxycodone HCl tablets (overdose). When you first start taking oxycodone HCl tablets, when your dose is changed, or if you take too much (overdose), serious or life-threatening breathing problems that can lead to death may occur. Talk to your healthcare provider about naloxone, a medicine for the emergency treatment of an opioid overdose. • Taking oxycodone HCl tablets with other opioid medicines, benzodiazepines, alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, decreased awareness, breathing problems, coma, and death. • Never give anyone else your oxycodone HCl tablets. They could die from taking it. Selling or giving away oxycodone HCl is against the law. • Store oxycodone HCl tablets securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Do not take oxycodone HCl tablets if you have: • severe asthma, trouble breathing, or other lung problems. • a bowel blockage or have narrowing of the stomach or intestines. • allergy to oxycodone. Before taking oxycodone HCl tablets, tell your healthcare provider if you have a history of: • head injury, seizures • liver, kidney, thyroid problems • problems urinating • pancreas or gallbladder problems • abuse of street or prescription drugs, alcohol addiction, opioid overdose, or mental health problems. Tell your healthcare provider if you are: • noticing your pain getting worse. If your pain gets worse after you take oxycodone HCl tablets, do not take more of oxycodone HCl tablets without first talking to your healthcare provider. Talk to your healthcare provider if the pain that you have increases, if you feel more sensitive to pain, or if you have new pain after taking oxycodone HCl tablets. • pregnant or planning to become pregnant. Use of oxycodone HCl tablets for an extended period of time during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated. • breastfeeding. Oxycodone HCl passes into breast milk and may harm your baby. Carefully observe infants for increased sleepiness (more than usual), breathing difficulties, or limpness. Seek immediate medical care if you notice these signs. • living in a household where there are small children or someone who has abused street or prescription drugs • taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking oxycodone HCl tablets with certain other medicines can cause serious side effects that could lead to death. When taking oxycodone HCl tablets: • Do not change your dose. Take oxycodone HCl tablets exactly as prescribed by your healthcare provider. Use the lowest dose possible for the shortest time needed. • For acute (short-term) pain, you may only need to take oxycodone HCl tablets for a few days. You may have some oxycodone HCl tablets left over that you did not use. See disposal information at the bottom of this section for directions on how to safely throw away (dispose of) your unused oxycodone HCl tablets. • Take your prescribed dose every 4 to 6 hours as needed for pain. Do not take more than your prescribed dose. If you miss a dose, take your next dose at your usual time. • Call your healthcare provider if the dose you are taking does not control your pain. • If you have been taking oxycodone HCl tablets regularly, do not stop taking oxycodone HCl tablets without talking to your healthcare provider. • Dispose of expired, unwanted, or unused oxycodone HCl by promptly flushing down the toilet, if a drug take-back option is not readily available. Visit www.fda.gov/drugdisposal for additional information on disposal of unused medicines. While taking oxycodone HCl tablets DO NOT: • Drive or operate heavy machinery, until you know how oxycodone HCl tablets affects you. Oxycodone HCl tablets can make you sleepy, dizzy, or lightheaded. • Drink alcohol or use prescription or over-the-counter medicines that contain alcohol. Using products containing alcohol during treatment with oxycodone HCl tablets may cause you to overdose and die. The possible side effects of oxycodone HCl tablets are: • constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain. Call your healthcare provider if you have any of these symptoms and they are severe. Get emergency medical help or call 911 right away if you have: • trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue, or throat, extreme drowsiness, light-headedness when changing positions, feeling faint, agitation, high body temperature, trouble walking, stiff muscles, or mental changes such as confusion. These are not all the possible side effects of oxycodone HCl tablets. Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov Manufactured by: Amneal Pharmaceuticals of NY, LLC Brookhaven, NY 11719 www.amneal.com or call 1-877-835-5472 Packaged and Distributed by: MAJOR® PHARMACEUTICALS Indianapolis, IN 46268 USA Refer to package label for Distributor's NDC Number This Medication Guide has been approved by the U.S. Food and Drug Administration. Rev. 04-2024-04
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Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.8.5 Geriatric Use Of the total number of subjects in clinical studies of oxycodone HCl, 20.8% (112/538) were 65 and over, while 7.2% (39/538) were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients (aged 65 years or older) may have increased sensitivity to oxycodone. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of oxycodone HCl slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see WARNINGS AND PRECAUTIONS (5.2) ] . Oxycodone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function.
Labor and delivery
Information about the drug’s use during labor or delivery, whether or not the use is stated in the indications section of the labeling, including the effect of the drug on the mother and fetus, on the duration of labor or delivery, on the possibility of delivery-related interventions, and the effect of the drug on the later growth, development, and functional maturation of the child.8.2 Lactation Risk Summary Available data from lactation studies indicate that oxycodone is present in breastmilk and that doses of less than 60 mg/day of the immediate-release formulation are unlikely to result in clinically relevant exposures in breastfed infants. A pharmacokinetics study utilizing opportunistic sampling of 76 lactating women receiving oxycodone immediate-release products for postpartum pain management showed that oxycodone concentrates in breastmilk with an average milk to plasma ratio of 3.2. The relative infant dose was low, approximately 1.3% of a weight-adjusted maternal dose (see Data ) . In the same study, among the 70 infants exposed to oxycodone in breastmilk, no adverse events were attributed to oxycodone. However, based on known adverse effects in adults, infants should be monitored for signs of excess sedation and respiratory depression (see Clinical Considerations ) . There are no data on the effects of the oxycodone on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for oxycodone HCl and any potential adverse effects on the breastfed infant from oxycodone HCl or from the underlying maternal condition. Clinical Considerations Monitor infants exposed to oxycodone HCl through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped or when breastfeeding is stopped. Data Oxycodone concentration data from 76 lactating women receiving immediate-release oxycodone products for postpartum pain management, and 28 infants exposed to oxycodone in breastmilk showed that following a median (range) dose of oxycodone in mothers of 9.2 (5 to 10) mg/dose or 33.0 (5.4 to 59.3) mg/day, oxycodone concentrated in breastmilk with a median (range) milk to plasma ratio of 3.2 (1.2 to 5.3). However, when using maternal breastmilk data to estimate the daily and relative infant dose, the infant dose was 0.006 mg/kg/day, which is 1.3% of a weight-adjusted maternal dose of 10 mg every 6 hours. These estimates based on maternal breastmilk concentrations were corroborated by the observed infant concentrations, of which over 75% (19/25) were below the limit of quantification. Among the 6 infants with quantifiable concentration, the median (range) concentration was 0.2 ng/mL (0.1 to 0.7). These concentrations are 100 to 1,000 times lower than concentrations observed in other studies after infants received oxycodone at 0.1 mg/kg/dose (~20 to 200 ng/mL).
Nursing mothers
Information about excretion of the drug in human milk and effects on the nursing infant, including pertinent adverse effects observed in animal offspring.8.3 Females and Males of Reproductive Potential Infertility Use of opioids for an extended period of time 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) ] .
Pediatric use
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.8.4 Pediatric Use The safety and efficacy of oxycodone HCl in pediatric patients have not been evaluated.
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)8.1 Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see WARNINGS AND PRECAUTIONS (5.4) ] . Available data with oxycodone HCl in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage or adverse maternal outcomes. Animal reproduction studies with oral administrations of oxycodone HCl in rats and rabbits during the period of organogenesis at doses 2.6 and 8.1 times, respectively, the human dose of 60 mg/day did not reveal evidence of teratogenicity or embryo-fetal toxicity. In several published studies, treatment of pregnant rats with oxycodone 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. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Use of opioid analgesics for an extended period of time 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 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 use, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see WARNINGS AND PRECAUTIONS (5.4) ] . Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. Oxycodone HCl is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including oxycodone HCl, can prolong labor through actions which temporarily reduce the strength, duration and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Data Animal Data In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of oxycodone HCl administered during the period of organogenesis up to 16 mg/kg/day and up to 25 mg/kg/day, respectively. These studies revealed no evidence of teratogenicity or embryo-fetal toxicity due to oxycodone. The highest doses tested in rats and rabbits were equivalent to approximately 2.6 and 8.1 times an adult human dose of 60 mg/day, respectively, on a mg/m 2 basis. In published studies, offspring of pregnant rats administered oxycodone during gestation have been reported to exhibit neurobehavioral effects including altered stress responses, increased anxiety-like behavior (2 mg/kg/day IV from Gestation Day 8 to 21 and Postnatal Day 1, 3, and 5; 0.3 times an adult human dose of 60 mg/day, on a mg/m 2 basis) and altered learning and memory (15 mg/kg/day orally from breeding through parturition; 2.4 times an adult human dose of 60 mg/day, on a mg/m 2 basis).
Use in specific populations
Information about use of the drug by patients in specific populations, including pregnant women and nursing mothers, pediatric patients, and geriatric patients.8 USE IN SPECIFIC POPULATIONS • Pregnancy: May cause fetal harm. ( 8.1 ) 8.1 Pregnancy Risk Summary Use of opioid analgesics for an extended period of time during pregnancy may cause neonatal opioid withdrawal syndrome [see WARNINGS AND PRECAUTIONS (5.4) ] . Available data with oxycodone HCl in pregnant women are insufficient to inform a drug-associated risk for major birth defects and miscarriage or adverse maternal outcomes. Animal reproduction studies with oral administrations of oxycodone HCl in rats and rabbits during the period of organogenesis at doses 2.6 and 8.1 times, respectively, the human dose of 60 mg/day did not reveal evidence of teratogenicity or embryo-fetal toxicity. In several published studies, treatment of pregnant rats with oxycodone 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. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Use of opioid analgesics for an extended period of time 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 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 use, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see WARNINGS AND PRECAUTIONS (5.4) ] . Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates. An opioid antagonist such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. Oxycodone HCl is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including oxycodone HCl, can prolong labor through actions which temporarily reduce the strength, duration and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression. Data Animal Data In embryo-fetal development studies in rats and rabbits, pregnant animals received oral doses of oxycodone HCl administered during the period of organogenesis up to 16 mg/kg/day and up to 25 mg/kg/day, respectively. These studies revealed no evidence of teratogenicity or embryo-fetal toxicity due to oxycodone. The highest doses tested in rats and rabbits were equivalent to approximately 2.6 and 8.1 times an adult human dose of 60 mg/day, respectively, on a mg/m 2 basis. In published studies, offspring of pregnant rats administered oxycodone during gestation have been reported to exhibit neurobehavioral effects including altered stress responses, increased anxiety-like behavior (2 mg/kg/day IV from Gestation Day 8 to 21 and Postnatal Day 1, 3, and 5; 0.3 times an adult human dose of 60 mg/day, on a mg/m 2 basis) and altered learning and memory (15 mg/kg/day orally from breeding through parturition; 2.4 times an adult human dose of 60 mg/day, on a mg/m 2 basis). 8.2 Lactation Risk Summary Available data from lactation studies indicate that oxycodone is present in breastmilk and that doses of less than 60 mg/day of the immediate-release formulation are unlikely to result in clinically relevant exposures in breastfed infants. A pharmacokinetics study utilizing opportunistic sampling of 76 lactating women receiving oxycodone immediate-release products for postpartum pain management showed that oxycodone concentrates in breastmilk with an average milk to plasma ratio of 3.2. The relative infant dose was low, approximately 1.3% of a weight-adjusted maternal dose (see Data ) . In the same study, among the 70 infants exposed to oxycodone in breastmilk, no adverse events were attributed to oxycodone. However, based on known adverse effects in adults, infants should be monitored for signs of excess sedation and respiratory depression (see Clinical Considerations ) . There are no data on the effects of the oxycodone on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for oxycodone HCl and any potential adverse effects on the breastfed infant from oxycodone HCl or from the underlying maternal condition. Clinical Considerations Monitor infants exposed to oxycodone HCl through breast milk for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped or when breastfeeding is stopped. Data Oxycodone concentration data from 76 lactating women receiving immediate-release oxycodone products for postpartum pain management, and 28 infants exposed to oxycodone in breastmilk showed that following a median (range) dose of oxycodone in mothers of 9.2 (5 to 10) mg/dose or 33.0 (5.4 to 59.3) mg/day, oxycodone concentrated in breastmilk with a median (range) milk to plasma ratio of 3.2 (1.2 to 5.3). However, when using maternal breastmilk data to estimate the daily and relative infant dose, the infant dose was 0.006 mg/kg/day, which is 1.3% of a weight-adjusted maternal dose of 10 mg every 6 hours. These estimates based on maternal breastmilk concentrations were corroborated by the observed infant concentrations, of which over 75% (19/25) were below the limit of quantification. Among the 6 infants with quantifiable concentration, the median (range) concentration was 0.2 ng/mL (0.1 to 0.7). These concentrations are 100 to 1,000 times lower than concentrations observed in other studies after infants received oxycodone at 0.1 mg/kg/dose (~20 to 200 ng/mL). 8.3 Females and Males of Reproductive Potential Infertility Use of opioids for an extended period of time 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) ] . 8.4 Pediatric Use The safety and efficacy of oxycodone HCl in pediatric patients have not been evaluated. 8.5 Geriatric Use Of the total number of subjects in clinical studies of oxycodone HCl, 20.8% (112/538) were 65 and over, while 7.2% (39/538) were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients (aged 65 years or older) may have increased sensitivity to oxycodone. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of oxycodone HCl slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see WARNINGS AND PRECAUTIONS (5.2) ] . Oxycodone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to regularly evaluate renal function. 8.6 Hepatic Impairment Because oxycodone is extensively metabolized in the liver, its clearance may decrease in patients with hepatic impairment. Initiate therapy in these patients with a lower than usual dosage of oxycodone HCl and titrate carefully. Regularly evaluate for adverse events such as respiratory depression, sedation, and hypotension [see CLINICAL PHARMACOLOGY (12.3) ] . 8.7 Renal Impairment Because oxycodone is known to be substantially excreted by the kidney, its clearance may decrease in patients with renal impairment. Initiate therapy with a lower than usual dosage of oxycodone HCl and titrate carefully. Regularly evaluate for adverse events such as respiratory depression, sedation, and hypotension [see CLINICAL PHARMACOLOGY (12.3) ] .
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.16 HOW SUPPLIED/STORAGE AND HANDLING Oxycodone HCl tablets, USP 5 mg are supplied as white, round, biconvex tablets debossed with “A” on the left and “04” on the right of the score on one side and plain on the other side. They are available as follows: Cartons of 100 tablets (10 tablet each blister pack x 10), NDC 0904-6966-61 Oxycodone HCl tablets, USP 15 mg are supplied as green, round, biconvex tablets debossed with “A” on the left and “49” on the right of the score on one side and plain on the other side. They are available as follows: Cartons of 100 tablets (10 tablet each blister pack x 10), NDC 0904-7180-61 DEA Order Form Required. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure. Protect from moisture. Store at 20° to 25°C (68° to 77°F); excursions are permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Store oxycodone HCl securely and dispose of properly [see PATIENT COUNSELING INFORMATION (17) ] .
Boxed warning
Information about contraindications or serious warnings, particularly those that may lead to death or serious injury.WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF OXYCODONE HCl Addiction, Abuse, and Misuse Because the use of oxycodone HCl exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see WARNINGS AND PRECAUTIONS (5.1) Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of oxycodone HCl, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of oxycodone HCl are essential [see WARNINGS AND PRECAUTIONS (5.2) ] . Accidental Ingestion Accidental ingestion of even one dose of oxycodone HCl, especially by children, can result in a fatal overdose of oxycodone [see WARNINGS AND PRECAUTIONS (5.2) ] . Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of oxycodone HCl and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see WARNINGS AND PRECAUTIONS (5.3) , DRUG INTERACTIONS (7) ] . Neonatal Opioid Withdrawal Syndrome (NOWS) If opioid use is required for an extended period of time in a pregnant woman, advise the patient of the risk of NOWS, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery [see WARNINGS AND PRECAUTIONS (5.4) ] . Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) Healthcare providers are strongly encouraged to complete a REMS-compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription [see WARNINGS AND PRECAUTIONS (5.5) ] . Cytochrome P450 3A4 Interaction The concomitant use of oxycodone HCl with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. Regularly evaluate patients receiving oxycodone HCl and any CYP3A4 inhibitor or inducer [see WARNINGS AND PRECAUTIONS (5.6) , DRUG INTERACTIONS (7) , CLINICAL PHARMACOLOGY (12.3) ] . WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF OXYCODONE HCl See full prescribing information for complete boxed warning. • Oxycodone HCl exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient’s risk before prescribing and reassess regularly for these behaviors and conditions. (5.1) • Serious, life-threatening, or fatal respiratory depression may occur, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of oxycodone HCl are essential. Error! Hyperlink reference not valid. • Accidental ingestion of oxycodone HCl, especially by children, can result in a fatal overdose of oxycodone. Error! Hyperlink reference not valid. • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation. (5.3 , 7) • If opioid use is required for an extended period of time in a pregnant woman, advise the patient of the risk of Neonatal Opioid Withdrawal Syndrome, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery. (5.4) • Healthcare providers are strongly encouraged to complete a REMS-compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription. (5.5) • Concomitant use with CYP3A4 inhibitors (or discontinuation of CYP3A4 inducers) can result in a fatal overdose of oxycodone from oxycodone HCl. (5.6 , 7 , 12.3)
Disclaimer: Do not rely on openFDA or Phanrmacy Near Me to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. Source: OpenFDA, Healthporta Drugs API