Oxycodone Hydrochloride Oral Solution Prescribing Information
Risk of Medication Errors
Ensure accuracy when prescribing, dispensing, and administering Oxycodone Hydrochloride Oral Solution. Dosing errors due to confusion between mg and mL, and other oxycodone hydrochloride oral solutions of different concentrations can results in accidental overdose.
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
Initiate the dosing regimen for each patient individually, taking into account the patient’s severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse
Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with Oxycodone Hydrochloride Oral Solution and adjust the dosage accordingly
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
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.
Oxycodone Hydrochloride Oral Solution exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death. Assess patient's risk prior to prescribing Oxycodone Hydrochloride Oral Solution, and monitor all patients regularly for the development of these behaviors and conditions.
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
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
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 REMS for these products
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:
• 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:
• 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.
• Counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
• Emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
• Consider other tools to improve patient, household, and community safety.
Serious, life-threatening, or fatal respiratory depression may occur with use of Oxycodone Hydrochloride Oral Solution. Monitor for respiratory depression, especially during initiation of Oxycodone Hydrochloride Oral Solution or following a dosage increase.
Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see Overdosage (10)].
Carbon dioxide (C02) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of Oxycodone Hydrochloride Oral Solution, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of Oxycodone Hydrochloride Oral Solution.
To reduce the risk of respiratory depression, proper dosing and titration of Oxycodone Hydrochloride Oral Solution are essential [see Dosage and Administration (2)]. Over estimating the Oxycodone Hydrochloride Oral Solution dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.
Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg/mL) is for use in opioid-tolerant patients only. Administration of this formulation may cause fatal respiratory depression when administered to patients who are not tolerant to the respiratory depressant effects of opioids.
Accidental ingestion of even one dose of Oxycodone Hydrochloride Oral Solution, especially by children, can result in respiratory depression and death due to an overdose of oxycodone.
Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [
Accidental ingestion of even one dose of Oxycodone Hydrochloride Oral Solution, especially by children, can result in a fatal overdose of oxycodone.
Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see Overdosage (10)].
Carbon dioxide (C02) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of Oxycodone Hydrochloride Oral Solution, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of Oxycodone Hydrochloride Oral Solution.
To reduce the risk of respiratory depression, proper dosing and titration of Oxycodone Hydrochloride Oral Solution are essential [see Dosage and Administration (2)]. Over estimating the Oxycodone Hydrochloride Oral Solution dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.
Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg/mL) is for use in opioid-tolerant patients only. Administration of this formulation may cause fatal respiratory depression when administered to patients who are not tolerant to the respiratory depressant effects of opioids.
Accidental ingestion of even one dose of Oxycodone Hydrochloride Oral Solution, especially by children, can result in respiratory depression and death due to an overdose of oxycodone.
Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [
Prolonged use of Oxycodone Hydrochloride Oral Solution during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
Prolonged use of Oxycodone Hydrochloride Oral Solution during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available
Concomitant use of Oxycodone Hydrochloride Oral Solution with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of oxycodone and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression
Concomitant use of Oxycodone Hydrochloride Oral Solution with CYP3A4 inducers or discontinuation of an CYP3A4 inhibitor could decrease oxycodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to oxycodone. When using Oxycodone Hydrochloride Oral Solution with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur
Table 1 includes 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) ] |
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 resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to oxycodone Clinical Pharmacology (12.3) ],[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 which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression. Clinical Pharmacology (12.3) ], |
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. |
Anticholinergic Drugs | |
Clinical Impact: | The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. |
Intervention: | Monitor patients for signs of urinary retention or reduced gastric motility when Oxycodone Hydrochloride Oral Solution is used concomitantly with anticholinergic drugs. |
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The activity of oxycodone hydrochloride is primarily due to the parent drug oxycodone.
About 60 to 87% of an oral dose reaches the systemic circulation in comparison to a parenteral dose. This high oral bioavailability (compared to other opioids) is due to lower pre-systemic and/or first-pass metabolism of oxycodone.
Food Effect
When oxycodone capsules are administered with a high-fat meal, mean AUC values are increased by 23% and peak concentrations are decreased by 14%. Food causes a delay in Tmax(1.00 to 3 hours). Similar effects of food are expected with the oral solution.
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.
Elimination
Metabolism
Oxycodone hydrochloride is extensively metabolized by multiple metabolic pathways to noroxycodone, oxymorphone, and noroxymorphone, which are subsequently glucuronidated. CYP3A4 mediated N-demethylation to noroxycodone is the primary metabolic pathway of oxycodone with a less contribution from CYP2D6 mediated O-demethylation to oxymorphone. Therefore, the formation of these and related metabolites can, in theory, be affected by other drugs. The major circulating metabolite is noroxycodone with an AUC ratio of 0.6 relative to that of oxycodone. Noroxycodone is reported to be a considerably weaker analgesic than oxycodone. Oxymorphone, although possessing analgesic activity, is present in the plasma only in low concentrations. The correlation between oxymorphone concentrations and opioid effects was much less than that seen with oxycodone plasma concentrations. The analgesic activity profile of other metabolites is not known.
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 is approximately 4 hours.
Specific Populations
Information obtained from oxycodone tablets indicate that the plasma concentrations of oxycodone did not appear to be increased in patients over of the age of 65.
Hepatic Impairment:
Because oxycodone is extensively metabolized in the liver, its clearance may decrease in hepatic-impaired patients. A dose adjustment is recommended in these patients
Because 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, a dose reduction is recommended for renal impaired patients
CYP3A4 Inhibitors
CYP3A4 is the major enzyme involved in noroxycodone formation. A published study showed that the co-administration of voriconazole, a CYP3A4 inhibitor, increased oxycodone AUC and Cmax by 3.6 and 1.7 fold, respectively.
CYP3A4 Inducers
A published study showed that the co-administration of rifampin, a drug metabolizing enzyme inducer, decreased oxycodone AUC and Cmax values by 86% and 63%, respectively.
CYP2D6 Inhibitors
Oxycodone is metabolized in part to oxymorphone via the cytochrome P450 isoenzyme CYP2D6. While this pathway may be blocked by a variety of drugs (e.g., certain cardiovascular drugs and antidepressants), such blockade has not yet been shown to be of clinical significance with this agent.
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
Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Oxycodone Hydrochloride Oral Solution with benzodiazepines and/or other CNS depressants including alcohol (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics
If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation.
Advise both patients and caregivers about the risks of respiratory depression and sedation when Oxycodone Hydrochloride Oral Solution are used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs
Table 1 includes 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) ] |
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 resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to oxycodone Clinical Pharmacology (12.3) ],[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 which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression. Clinical Pharmacology (12.3) ], |
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. |
Anticholinergic Drugs | |
Clinical Impact: | The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. |
Intervention: | Monitor patients for signs of urinary retention or reduced gastric motility when Oxycodone Hydrochloride Oral Solution is used concomitantly with anticholinergic drugs. |
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• Reserve concomitant prescribing of Oxycodone Hydrochloride Oral Solution and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
• Limit dosages and durations to the minimum required.
• Follow patients for signs and symptoms of respiratory depression and sedation.
Dosage and Administration (2.3,2.4) 10/2019
Warnings and Precautions (
Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see Overdosage (10)].
Carbon dioxide (C02) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of Oxycodone Hydrochloride Oral Solution, the risk is greatest during the initiation of therapy or following a dosage increase. Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of Oxycodone Hydrochloride Oral Solution.
To reduce the risk of respiratory depression, proper dosing and titration of Oxycodone Hydrochloride Oral Solution are essential [see Dosage and Administration (2)]. Over estimating the Oxycodone Hydrochloride Oral Solution dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.
Oxycodone Hydrochloride Oral Solution 100 mg per 5 mL (20 mg/mL) is for use in opioid-tolerant patients only. Administration of this formulation may cause fatal respiratory depression when administered to patients who are not tolerant to the respiratory depressant effects of opioids.
Accidental ingestion of even one dose of Oxycodone Hydrochloride Oral Solution, especially by children, can result in respiratory depression and death due to an overdose of oxycodone.
Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia. Opioid use increases the risk of CSA in a dose-dependent fashion. In patients who present with CSA, consider decreasing the opioid dosage using best practices for opioid taper [
Do not abruptly discontinue Oxycodone Hydrochloride Oral Solution in a patient physically dependent on opioids. When discontinuing Oxycodone Hydrochloride Oral Solution in a physically-dependent patient, gradually taper the dosage. Rapid tapering of oxycodone in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain [see
Additionally, avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) analgesics in patients who are receiving full opioid agonist analgesic, including Oxycodone Hydrochloride Oral Solution. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms [
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.
Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses,
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
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
• 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 100 mg per 5 mL (20 mg/mL) is for opioid-tolerant patients only () Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.
2.1 Important Dosage and Administration InstructionsOxycodone 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)].)2.1 Important Dosage and Administration InstructionsOxycodone 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)]. - Individualize dosing based on the severity of pain, patient response, prior analgesic experience, and risk factor for addiction, abuse, and misuse. ()
2.1 Important Dosage and Administration InstructionsOxycodone 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)]. - Initiate dosing with a range of 5 to 15 mg every 4 to 6 hours as needed for pain. ()
2.2 Initial DosageAlthough 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 AnalgesicDo 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 SolutionThere 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. If a patient has been receiving opioid-containing medications prior to taking Oxycodone Hydrochloride Oral Solution, 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 Hydrochloride Oral Solution close observation and adjustment of dosage based upon the patient’s response to Oxycodone Hydrochloride Oral Solution is imperative. Administration of supplemental analgesia for breakthrough or incident pain and titration of the total daily dose of Oxycodone Hydrochloride Oral Solution may be necessary, especially in patients who have disease states that are changing rapidly.
Conversion from Oxycodone Hydrochloride Oral Solution to Extended-Release Oxycodone HydrochlorideThe relative bioavailability of Oxycodone Hydrochloride Oral Solution compared to extended-release oxycodone is unknown, so conversion to extended-release tablets must be accompanied by close observation for signs of excessive sedation and respiratory depression
. - 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 Initial DosageAlthough 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 AnalgesicDo 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 SolutionThere 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. If a patient has been receiving opioid-containing medications prior to taking Oxycodone Hydrochloride Oral Solution, 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 Hydrochloride Oral Solution close observation and adjustment of dosage based upon the patient’s response to Oxycodone Hydrochloride Oral Solution is imperative. Administration of supplemental analgesia for breakthrough or incident pain and titration of the total daily dose of Oxycodone Hydrochloride Oral Solution may be necessary, especially in patients who have disease states that are changing rapidly.
Conversion from Oxycodone Hydrochloride Oral Solution to Extended-Release Oxycodone HydrochlorideThe relative bioavailability of Oxycodone Hydrochloride Oral Solution compared to extended-release oxycodone is unknown, so conversion to extended-release tablets must be accompanied by close observation for signs of excessive sedation and respiratory depression
. - Individually titrate Oxycodone Hydrochloride Oral Solution to a dose that provides adequate analgesia and minimizes adverse reactions. ()
2.3 Titration and Maintenance of TherapyIndividually titrate Oxycodone Hydrochloride Oral Solution to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving Oxycodone Hydrochloride Oral Solution to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse
[see Warnings and Precautions (5.2)].
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 Hydrochloride Oral Solution dosage. If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions. - 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 Safe Reduction or Discontinuation of Oxycodone Hydrochloride Oral SolutionDo not abruptly discontinue Oxycodone Hydrochloride Oral Solution 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 Hydrochloride Oral Solution, there are a variety of factors that should be considered, including the dose of Oxycodone Hydrochloride Oral Solution 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 co-morbid 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 Hydrochloride Oral Solution 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, monitor 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 a long duration 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)]
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.
•
Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome
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.
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
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.
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/m2basis. 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/m2basis) 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/m2basis).