Oxycodone Hydrochloride Oral Solution
Solution · Oral
Uses
Oxycodone Hydrochloride Oral Solution is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg/mL) is indicated for the relief of pain in opioid-tolerant patients. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, [see Warnings and Precautions (5.2) ], reserve Oxycodone Hydrochloride Oral Solution 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 Hydrochloride Oral Solution is 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 (1) Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve Oxycodone Hydrochloride Oral Solution 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
Dosage and administration
Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg/mL) is for opioid-tolerant patients only ( 2.1 ) Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. (2.1 ) Individualize dosing based on the severity of pain, patient response, prior analgesic experience, and risk factor for addiction, abuse, and misuse. ( 2.1 ) Initiate dosing with a range of 5 to 15 mg every 4 to 6 hours as needed for pain. ( 2.2 ) For control of chronic pain, administer Oxycodone Hydrochloride Oral Solution on a regularly scheduled basis, at the lowest dosage level to achieve adequate analgesia. ( 2.2 ) Individually titrate Oxycodone Hydrochloride Oral Solution to a dose that provides adequate analgesia and minimizes adverse reactions. ( 2.3 ) Do not abruptly discontinue Oxycodone Hydrochloride Oral Solution in a physically dependent patient because rapid discontinuation of Opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. ( 2.4 ) 2.1 Important Dosage and Administration Instructions Oxycodone Hydrochloride Oral Solution is available in two concentrations: 5 mg per 5 mL (1 mg/mL), and 100 mg per 5 mL (20 mg/mL). Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg/mL) is for use in opioid-tolerant patients only who have already been receiving opioid therapy. Use this strength only for patients who have already been titrated to a stable analgesic regimen using lower strengths of oxycodone hydrochloride and who can benefit from use of a smaller volume of oral solution. Patients considered to be opioid tolerant are those who are receiving, for one week or longer, at least 60mg oral morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid. Ensure accuracy when prescribing, dispensing, and administering Oxycodone Hydrochloride Oral Solution to avoid dosing errors due to confusion between mg and mL, and with other oxycodone hydrochloride solutions of different concentrations, which could result in accidental overdose and death. Ensure the proper dose is communicated and dispensed. When writing prescriptions, include both the total dose in mg and the total dose in volume. Always use the enclosed calibrated measuring cup when administering Oxycodone Hydrochloride Oral Solution 5 mg per 5 mL and always use the enclosed calibrated oral syringe when administering Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg per mL) to ensure that the dose is measured and administered accurately. Do not use household teaspoons or tablespoons to measure Oxycodone Hydrochloride Oral Solution, as using a tablespoon instead of a teaspoon could lead to overdosage. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions (5) ]. Initiate the dosing regimen for each patient individually, taking into account the patient’s severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.2) ]. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with Oxycodone Hydrochloride Oral Solution and adjust the dosage accordingly [see Warnings and Precautions (5.4) ]. 2.2 Initial Dosage Although it is not possible to list every condition that is important to the selection of the initial dose of Oxycodone Hydrochloride Oral Solution, 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 Hydrochloride Oral Solution as the First Opioid Analgesic Do not initiate treatment with Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg per mL) in patients who are opioid naïve. Select an alternate product with lower concentration. Initiate treatment with Oxycodone Hydrochloride Oral Solution in a dosing range of 5 to 15 mg every 4 to 6 hours as needed for pain. Titrate the dose based upon the individual patient’s response to their initial dose of Oxycodone Hydrochloride Oral Solution. Patients with chronic pain should have their dosage given on an around-the-clock basis to prevent the reoccurrence of pain rather than treating the pain after it has occurred. This dose can then be adjusted to an acceptable level of analgesia taking into account side effects experienced by the patient. For control of severe chronic pain, Oxycodone Hydrochloride Oral Solution should be administered on a regularly scheduled basis, every 4 to 6 hours, at the lowest dosage level that will achieve adequate analgesia. Conversion from Other Opioids to Oxycodone Hydrochloride Oral Solution 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 Hydrochloride Oral Solution. It is safer to underestimate a patient’s 24-hour Oxycodone Hydrochloride Oral Solution dosage than to overestimate the 24-hour Oxycodone Hydrochloride Oral Solution dosage and manage an adverse reaction due to overdose.
Dosage forms and strengths
Oxycodone Hydrochloride Oral Solution, USP 5 mg per 5 mL (1 mg/mL) Strength Oral Solution: Each 5 mL of red Oxycodone Hydrochloride Oral Solution, USP contains oxycodone hydrochloride 5 mg. 100 mg per 5 mL (20 mg per mL) Strength Oral Solution: Each 5 mL of yellow Oxycodone Hydrochloride Oral Solution, USP contains oxycodone hydrochloride 100 mg. Oral Solution
• 5 mg per 5 mL (1 mg/mL)
• 100 mg per 5 mL (20 mg/ mL): (3)
Contraindications
Oxycodone Hydrochloride Oral Solution is contraindicated in patients with:
• Significant respiratory depression [see Warnings and Precautions (5.4)]
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.8)]
• Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.12)]
• Hypersensitivity to oxycodone (e.g., angioedema) [see Adverse Reactions (6)]
• Significant respiratory depression (4)
• Acute or severe bronchial asthma in an unmonitored setting in absence of resuscitative equipment. (4)
• Known or suspected gastrointestinal obstruction, including paralytic ileus. (4)
• Hypersensitivity to oxycodone. (4)
Warnings and precautions
• Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients: Monitor closely, particularly during initiation and titration.( 5.8)
• Adrenal Insufficiency: If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. ( 5.9 )
• Severe Hypotension: Monitor during dosage initiation and titration. Avoid use of Oxycodone Hydrochloride Oral Solution in patients with circulatory shock .(5.10)
• Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness: Monitor for sedation and respiratory depression. Avoid use of Oxycodone Hydrochloride Oral Solution in patients with impaired consciousness or coma. ( 5.11 ) 5.1 Risk of Accidental Overdose and Death due to Medication Errors Dosing errors can result in accidental overdose and death. Avoid dosing errors that may result from confusion between mg and mL and confusion with oxycodone hydrochloride solutions of different concentrations, when prescribing, dispensing, and administering Oxycodone Hydrochloride Oral Solution. Ensure that the dose is communicated clearly and dispensed accurately. Always use the enclosed calibrated measuring cup when administering Oxycodone Hydrochloride Oral Solution 5 mg per 5 mL (1 mg/mL) and always use the enclosed calibrated oral syringe when administering Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg/ mL) to ensure the dose is measured and administered accurately. Do not use a teaspoon or a tablespoon to measure a dose. A household teaspoon or tablespoon is not an adequate measuring device. Given the inexactitude of the household spoon measure and the possibility of using a tablespoon instead of a teaspoon, which could lead to overdosage, it is strongly recommended that, if the enclosed calibrated measuring cup becomes lost, caregivers obtain and use a calibrated measuring device. Health care providers should recommend a calibrated device that can measure and deliver the prescribed dose accurately, and instruct caregivers to use extreme caution in measuring the dosage. 5.2 Addiction, Abuse, and Misuse Oxycodone Hydrochloride Oral Solution contains oxycodone, a Schedule II controlled substance. As an opioid, Oxycodone Hydrochloride Oral Solution exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9) ]. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Oxycodone Hydrochloride Oral Solution. Addiction can occur at recommended dosages and if the drug is misused or abused. Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing Oxycodone Hydrochloride Oral Solution, and monitor all patients receiving Oxycodone Hydrochloride Oral Solution for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient. Patients at increased risk may be prescribed opioids such as Oxycodone Hydrochloride Oral Solution, but use in such patients necessitates intensive counseling about the risks and proper use of Oxycodone Hydrochloride Oral Solution along with intensive monitoring for signs of addiction, abuse, and misuse. Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing Oxycodone Hydrochloride Oral Solution. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see Patient Counseling Information (17) ]. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product. 5.3 Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation Strategy (REMS) for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers. Healthcare providers are strongly encouraged to do all of the following:
• Complete a REMS compliant education program offered by an accredited provider of continuing education (CE) or another education program that includes all the elements of the FDA Education Blueprint for Health Care Providers Involved in the Management or Support of Patients with Pain.
• Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with patients and/or their caregivers every time these medicines are prescribed. The Patient Counseling Guide (PCG) can be obtained at this link: www.fda.gov/OpioidAnalgesicREMSPCG.
• Emphasize to patients and their caregivers the importance of reading the Medication Guide that they will receive from their pharmacist every time an opioid analgesic is dispensed to them.
• Consider using other tools to improve patient, household, and community safety, such as patient-prescriber agreements that reinforce patient prescriber responsibilities. To obtain further information on the opioid analgesic REMS and for a list of accredited REMS CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com. The FDA Blueprint can be found at www.fda/gov/OpioidAnalgesicREMSBlueprint. 5.4 Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended.
Side effects
The following serious adverse reactions are described, or described in greater detail, in other sections:
• Addiction, Abuse, and Misuse [see Warnings and Precautions (5.2)]
• Life-Threatening Respiratory Depression [see Warnings and Precautions (5.4)]
• Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.5)]
• Interactions with Benzodiazepines or Other CNS Depressants [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)] The following adverse reactions associated with the use of oxycodone were identified in clinical studies or post marketing reports. Because some of these reactions were 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. Serious adverse reactions associated with oxycodone 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 are dose-related and are typical opioid-related adverse reactions. The most frequent adverse events include nausea, constipation, vomiting, headache, and pruritus. 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 another formulation of immediate-release oxycodone, the following adverse events were recorded in oxycodone treated patients with an incidence ≥ 3%. In descending order of frequency, they were: nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence. The other less frequently observed adverse reactions from opioid analgesics, including Oxycodone Hydrochloride Oral Solution included: Body as a Whole: abdominal pain, accidental injury, allergic reaction, back pain, chills and fever, fever, flu syndrome, infection, neck pain, pain, photosensitivity reaction, and sepsis. Cardiovascular: deep thrombophlebitis, heart failure, hemorrhage, hypotension, migraine, palpitation, and tachycardia. Digestive : anorexia, diarrhea, dyspepsia, dysphagia, gingivitis, glossitis, and nausea and vomiting. Hemic and Lymphatic: anemia and leukopenia. Metabolic and Nutritional: edema, gout, hyperglycemia, iron deficiency anemia and peripheral edema. Musculoskeletal: arthralgia, arthritis, bone pain, myalgia and pathological fracture. Nervous: agitation, anxiety, confusion, dry mouth, hypertonia, hypesthesia, nervousness, neuralgia, personality disorder, tremor, and vasodilation. Respiratory: bronchitis, cough increased, dyspnea, epistaxis, laryngismus, lung disorder, pharyngitis, rhinitis, and sinusitis. Skin and Appendages: herpes simplex, rash, sweating, and urticaria. Special Senses: amblyopia. Urogenital: urinary tract infection Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Anaphylaxis: Anaphylaxis has been reported with ingredients contained in Oxycodone Hydrochloride Oral Solution. Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see Clinical Pharmacology (12.2) ]. Most common adverse reactions are nausea, constipation, vomiting, headache, pruritus, insomnia, dizziness, asthenia, and somnolence. (6) To report SUSPECTED ADVERSE REACTIONS, contact Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov.medwatch .
Drug interactions
Table 1 includes clinically significant drug interactions with Oxycodone Hydrochloride Oral Solution. Table 1: Clinically Significant Drug Interactions with Oxycodone Hydrochloride Oral Solution Inhibitors of CYP3A4 and CYP2D6 Clinical Impact: The concomitant use of Oxycodone Hydrochloride Oral Solution 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 Hydrochloride Oral Solution and CYP2D6 and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of Oxycodone Hydrochloride Oral Solution is achieved [see Warnings and Precautions (5.6) ]. 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 Hydrochloride Oral Solution until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the Oxycodone Hydrochloride Oral Solution dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Example 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 Hydrochloride Oral Solution 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 Hydrochloride Oral Solution dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider Oxycodone Hydrochloride Oral Solution dosage reduction and monitor for signs of respiratory depression. Examples Rifampin, carbamazepine, phenytoin Benzodiazepines and other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants including alcohol, increases the risk of respiratory depression, profound sedation, coma, and death. Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation [see Warnings and Precautions (5.7) ] . Examples Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol. Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue Oxycodone Hydrochloride Oral Solution 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 (5.4) ]. Intervention: The use of Oxycodone Hydrochloride Oral Solution 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 and Partial Agonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of Oxycodone Hydrochloride Oral Solution and/or precipitate withdrawal symptoms. Intervention: Avoid concomitant use. Examples: butorphanol, nalbuphine, pentazocine, buprenorphine Muscle Relaxants Clinical Impact: Oxycodone may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Intervention: Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of Oxycodone Hydrochloride Oral Solution and/or the muscle relaxant as necessary. Diuretics Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Intervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.
Use in specific populations
• Pregnancy: May cause fetal harm. (8.1) 8.1 Pregnancy Risk Summary Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.5) ]. Available data with Oxycodone Hydrochloride Oral Solution are insufficient to inform a drug-associated risk for major birth defects and miscarriage. Animal reproduction studies with oral administrations of oxycodone hydrochloride 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. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, 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 (5.5)]. 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 Hydrochloride Oral Solution 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 Hydrochloride Oral Solution, 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 hydrochloride administered during the period of organogenesis up to 16 mg/kg/day and up 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 Oxycodone is present in breast milk. Published lactation studies report variable concentrations of oxycodone in breast milk with administration of immediate-release oxycodone to nursing mothers in the early postpartum period. The lactation studies did not assess breastfed infants for potential adverse reactions. Lactation studies have not been conducted with Oxycodone Hydrochloride Oral Solution, and no information is available on the effects of the drug on the breastfed infant or the effects of the drug on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Oxycodone Hydrochloride Oral Solution and any potential adverse effects on the breastfed infant from Oxycodone Hydrochloride Oral Solution or from the underlying maternal condition. Clinical Considerations Monitor infants exposed to Oxycodone Hydrochloride Oral Solution 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 breast-feeding is stopped. 8.3 Females and Males of Reproductive Potential Infertility Chronic use of opioids may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Adverse Reactions (6), Clinical Pharmacology (12.2) ]. 8.4 Pediatric Use The safety and effectiveness and the pharmacokinetics of Oxycodone Hydrochloride Oral Solution in pediatric patients below the age of 18 have not been established. 8.5 Geriatric Use Elderly patients (aged 65 years or older) may have increased sensitivity to oxycodone. In general, use caution when selecting a dose 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.
Pregnancy
8.1 Pregnancy Risk Summary Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions (5.5) ]. Available data with Oxycodone Hydrochloride Oral Solution are insufficient to inform a drug-associated risk for major birth defects and miscarriage. Animal reproduction studies with oral administrations of oxycodone hydrochloride 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. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, 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 (5.5)]. 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 Hydrochloride Oral Solution 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 Hydrochloride Oral Solution, 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 hydrochloride administered during the period of organogenesis up to 16 mg/kg/day and up 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).
Pediatric use
8.4 Pediatric Use The safety and effectiveness and the pharmacokinetics of Oxycodone Hydrochloride Oral Solution in pediatric patients below the age of 18 have not been established.
Geriatric use
8.5 Geriatric Use Elderly patients (aged 65 years or older) may have increased sensitivity to oxycodone. In general, use caution when selecting a dose 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 Hydrochloride Oral Solution slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see Warnings and Precautions (5.8)]. 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.
Overdosage
Clinical Presentation Acute overdose with Oxycodone Hydrochloride Oral Solution can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology (12.2) ]. Treatment of Overdose In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques. The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to oxycodone overdose, administer an opioid antagonist. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to oxycodone overdose. Because the duration of opioid reversal is expected to be less than the duration of action of oxycodone in Oxycodone Hydrochloride Oral Solution, carefully monitor the patient until spontaneous respiration is reliably re-established. 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.
Description
Oxycodone Hydrochloride Oral Solution is an agonist, available as a red solution 5 mg/5 mL (1 mg/mL) and a yellow solution 100 mg/5 mL (20 mg/mL) for oral administration. The chemical name is (5R, 9R, 13S, 14S)-4, 5α-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one hydrochloride. The molecular weight is 351.82. Its molecular formula is C18H21NO4.HCl, and it has the following chemical structure. Oxycodone hydrochloride is a white, odorless crystalline powder derived from the opium alkaloid, thebaine. It is soluble in water and slightly soluble in alcohol. The inactive ingredients in Oxycodone Hydrochloride Oral Solution, 5 mg per 5 mL (1mg/mL) include: Sodium Saccharin, Sorbitol, Sodium Benzoate, Citric Acid Anhydrous, Sodium Citrate Dihydrate, Purified Water, FD&C Red No. 40. Natural and artificial berry flavor contains: Natural flavors, propylene glycols and Water. The inactive ingredients in Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg/ mL): include: Citric Acid Anhydrous, D&C Yellow No. 10, Purified Water, Sodium Citrate Dihydrate, Sodium Benzoate, Sodium Saccharin, and Sorbitol.Natural and artificial berry flavor contains: Natural flavors, propylene glycols and Water. structure.jpg
Mechanism of action
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.
How supplied
Oxycodone Hydrochloride Oral Solution 5 mg per 5 mL (1 mg/mL), is a red solution, supplied as: NDC# 13107-261-58: Bottle of 500 mL supplied with a calibrated measuring cup. Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg per mL), is a yellow solution, supplied as: NDC# 13107-262-57: Bottle of 30 mL supplied with a calibrated oral syringe. Store: Store at Controlled Room Temperature, 25°C (77°F); excursions are permitted to 15° - 30°C (59° - 86°F). PROTECT from MOISTURE and LIGHT. Store Oxycodone Hydrochloride Oral Solution securely and dispose of properly [ see Patient Counseling Information (17) ].
Patient 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 Hydrochloride Oral Solution 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 Hydrochloride Oral Solution unsecured can pose a deadly risk to others in the home (see Warnings and Precautions (5.2, 5.14), 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 Hydrochloride Oral Solution 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. Medication Errors Advise patients that Oxycodone Hydrochloride Oral Solution, is available in two concentrations (5 mg/5 mL and 100 mg/5 mL). Inform patients about which concentration they have been prescribed. Instruct patients how to measure and take the correct dose of Oxycodone Hydrochloride Oral Solution and to always use the enclosed calibrated measuring cup when administering Oxycodone Hydrochloride Oral Solution 5 mg per 5 mL (1 mg/mL) and to always use the enclosed calibrated oral syringe when administering Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg/mL) to ensure the dose is measured and administered accurately [see Warnings and Precautions (5.1) ]. If the prescribed concentration is changed, instruct patients on how to correctly measure the new dose to avoid errors which could result in accidental overdose and death. Addiction, Abuse, and Misuse Inform patients that the use of Oxycodone Hydrochloride Oral Solution, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see Warnings and Precautions (5.2) ]. Instruct patients not to share Oxycodone Hydrochloride Oral Solution with others and to take steps to protect Oxycodone Hydrochloride Oral Solution from theft or 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 Hydrochloride Oral Solution or when the dosage is increased, and that it can occur even at recommended dosages [see Warnings and Precautions (5.4) ]. Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop. Accidental Ingestion Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see Warnings and Precautions (5.4) ]. Interactions with Benzodiazepines and Other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur if Oxycodone Hydrochloride Oral Solution is used with benzodiazepines or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a health care provider [see Warnings and Precautions (5.7) , Drug Interactions (7) ]. 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 medications. [see Drug Interactions (7) ]. MAOI Interaction Inform patients to avoid taking Oxycodone Hydrochloride Oral Solution while using any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while taking Oxycodone Hydrochloride Oral Solution [see Drug Interactions (7) ]. 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) ]. Important Administration Instructions Instruct patients how to properly take Oxycodone Hydrochloride Oral Solution. [see Dosage and Administration (2.1) , Warnings and Precautions (5.1) ].
• Advise patients to always use the enclosed calibrated oral syringe/dosing cup when administering Oxycodone Hydrochloride Oral Solution to ensure the dose is measured and administered accurately [see Warnings and Precautions (5.1) ].
• Advise patients never to use household teaspoons or tablespoons to measure Oxycodone Hydrochloride Oral Solution.
• Inform patients that the 100 mg per 5 mL (20 mg/mL) formulation is only for patients who are already receiving opioid-therapy and have demonstrated opioid- tolerance. Use of this formulation may cause fatal respiratory depression when administered to patients who have not had previous exposure to opioids [ see I ndications and Usage (1) , see Dosage and Administration (2.1) ].
• Advise patients not to adjust the dose of Oxycodone Hydrochloride Oral Solution without consulting with a physician or other healthcare provider. Important Discontinuation Instructions In order to avoid developing withdrawal symptoms, instruct patients not to discontinue Oxycodone Hydrochloride Oral Solution without first discussing a tapering plan with the prescriber [ see Dosage and Administration (2.4) ]. Hypotension Inform patients that Oxycodone Hydrochloride Oral Solution may cause orthostatic hypotension and syncope.
Label text from the FDA structured product label by Aurolife Pharma, LLC (revised Jan 18, 2024). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Oxycodone Hydrochloride in 2 products
Oxycodone Hydrochloride Oral Solution NDC products (2)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 13107-261 | Oxycodone Hydrochloride 5 mg/5mL Solution | Aurolife Pharma, LLC | ANDA · DEA CII |
| 13107-262 | Oxycodone Hydrochloride 100 mg/5mL Solution | Aurolife Pharma, LLC | ANDA · DEA CII |
Frequently asked questions
What is Oxycodone Hydrochloride Oral Solution used for?
Oxycodone Hydrochloride Oral Solution is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg/mL) is indicated for the relief of pain in opioid-tolerant patients. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, even at…
What are the side effects of Oxycodone Hydrochloride Oral Solution?
The following serious adverse reactions are described, or described in greater detail, in other sections: • Addiction, Abuse, and Misuse [see Warnings and Precautions (5.2)] • Life-Threatening Respiratory Depression [see Warnings and Precautions (5.4)] • Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.5)] • Interactions with Benzodiazepines or Other CNS Depressants [see… See the full label for the complete list.
Who makes Oxycodone Hydrochloride Oral Solution?
Oxycodone Hydrochloride Oral Solution is listed by 1 labeler in the FDA NDC directory, including Aurolife Pharma, LLC.