Oxycodone Hydrochloride And Acetaminophen - Oxycodone Hydrochloride And Acetaminophen solution prescribing information
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF OXYCODONE HYDROCHLORIDE AND ACETAMINOPHEN ORAL SOLUTION
Risk of Medication Errors Ensure accuracy when prescribing, dispensing, and administering oxycodone hydrochloride and acetaminophen oral solution 10 mg/300 mg per 5 mL. Dosing errors due to confusion between mg and mL, and other oxycodone hydrochloride and acetaminophen oral solutions of different concentrations can result in accidental overdose and death [see WARNINGS , DOSAGE AND ADMINISTRATION ]. Addiction, Abuse, and Misuse Because the use of oxycodone hydrochloride and acetaminophen oral solution exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see WARNINGS ]. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of oxycodone hydrochloride and acetaminophen oral solution, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of oxycodone hydrochloride and acetaminophen oral solution are essential [see WARNINGS ]. Accidental Ingestion Accidental ingestion of even one dose of oxycodone hydrochloride and acetaminophen oral solution, especially by children, can result in a fatal overdose of oxycodone [see WARNINGS ]. Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of oxycodone hydrochloride and acetaminophen oral solution and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. [see WARNINGS , PRECAUTIONS; Drug Interactions ]. Neonatal Opioid Withdrawal Syndrome (NOWS) If opioid use is required for an extended period of time in a pregnant woman, advise the patient of the risk of NOWS, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery [see WARNINGS ]. Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) Healthcare providers are strongly encouraged to complete a REMS-compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription [see WARNINGS ]. Cytochrome P450 3A4 Interaction The concomitant use of oxycodone hydrochloride and acetaminophen oral solution with all cytochrome P450 3A4 inhibitors may result in an increase in oxycodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration. Monitor patients receiving oxycodone hydrochloride and acetaminophen oral solution and any CYP3A4 inhibitor or inducer [see CLINICAL PHARMACOLOGY , WARNINGS , PRECAUTIONS; Drug Interactions ]. Hepatotoxicity Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 mg per day, and often involve more than one acetaminophen-containing product [see WARNINGS ].
INDICATIONS AND USAGE
Oxycodone hydrochloride and acetaminophen oral solution is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.
Limitations of Use
Because of the risks of addiction, abuse, and misuse, with opioids, which can occur at any dosage or duration [see WARNINGS ], reserve oxycodone hydrochloride and acetaminophen oral solution for use in patients for whom alternative treatment options [e.g., non-opioid analgesics]:
- 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 and acetaminophen oral solution should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.
DOSAGE AND ADMINISTRATION
Important Dosage and Administration Instructions
Ensure accuracy when prescribing, dispensing, and administering oxycodone hydrochloride and acetaminophen oral solution to avoid dosing errors due to confusion between mg and mL, and with other oxycodone hydrochloride and acetaminophen 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.
Instruct patients and caregivers on how to accurately measure and take or administer the correct dose of oxycodone hydrochloride and acetaminophen oral solution. Strongly advise patients and caregivers to always use a graduated oral syringe or measuring cup, with metric units of measurements (i.e., mL), to correctly measure the prescribed amount of medication. Inform patients and caregivers that oral dosing devices may be obtained from their pharmacy and to never use household teaspoons or tablespoons to measure oxycodone hydrochloride and acetaminophen oral solution.
Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see WARNINGS ]. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of oxycodone hydrochloride and acetaminophen oral solution for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see WARNINGS ]. Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with oxycodone hydrochloride and acetaminophen oral solution. Consider this risk when selecting an initial dose and when making dose adjustments [see WARNINGS ].
Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose
Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with oxycodone hydrochloride and acetaminophen oral solution [see WARNINGS ; Life-Threatening Respiratory Depression , PRECAUTIONS; Information for Patients ]. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing regulations (e.g., by prescription, directly from a pharmacist, or as part of a community-based program). Consider prescribing naloxone, based on the patient’s risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient [see WARNINGS; Addiction, Abuse, and Misuse , Life-Threatening Respiratory , Depression , Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants ].
Consider prescribing naloxone when the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose.
Initial Dosage
Use of Oxycodone Hydrochloride and Acetaminophen Oral Solution as the First Opioid Analgesic Initiate treatment with oxycodone hydrochloride and acetaminophen oral solution at a dose of 5 mL (one teaspoonful) every 6 hours as needed for pain, at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient's response to their initial dose of oxycodone hydrochloride and acetaminophen oral solution. The total daily dose of acetaminophen should not exceed 4 grams. (Maximum daily dose is 6 teaspoonfuls or 30 mL.)
It is of utmost importance that the dose of oxycodone hydrochloride and acetaminophen oral solution be administered accurately. A household teaspoon or tablespoon is not an adequate measuring device, especially when one-half or three-fourths of a teaspoonful is to be measured. Given the variability of the household spoon measure and the possibility of mistakenly using a tablespoon instead of a teaspoon, which could lead to overdosage, it is strongly recommended that caregivers obtain and use a calibrated measuring device. Health care providers should recommend a calibrated measuring device that can measure and deliver the prescribed dose accurately, and instruct caregivers to use extreme caution in measuring the dosage.
Conversion from Oxycodone Hydrochloride and Acetaminophen Oral Solution to Extended-Release Oxycodone
The relative bioavailability of oxycodone hydrochloride and acetaminophen oral solution compared to extended-release oxycodone is unknown, so conversion to extended-release oxycodone may lead to increased risk of of excessive sedation and respiratory depression.
Titration and Maintenance of Therapy
Individually titrate oxycodone hydrochloride and acetaminophen oral solution to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving oxycodone hydrochloride and acetaminophen oral solution to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions, as well as reassessing for the development of addiction, abuse, or misuse [see WARNINGS]. 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 and acetaminophen oral solution dosage. If after increasing the dosage, unacceptable opioid-related adverse reactions are observed (including an increase in pain after dosage increase), consider reducing the dosage [see WARNINGS ]. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.
Safe Reduction or Discontinuation of Oxycodone Hydrochloride and Acetaminophen Oral Solution
Do not abruptly discontinue oxycodone hydrochloride and acetaminophen 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 and acetaminophen oral solution, there are a variety of factors that should be considered, including the total daily dose of opioid (including oxycodone hydrochloride and acetaminophen 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 and acetaminophen 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, evaluate patients for any changes in mood, emergence of suicidal thoughts, or use of other substances.
When managing patients taking opioid analgesics, particularly those who have been treated for an extended period of time, and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic [see WARNINGS; Withdrawal , DRUG ABUSE AND DEPENDENCE ].
CONTRAINDICATIONS
Oxycodone hydrochloride and acetaminophen oral solution is contraindicated in patients with:
- Significant respiratory depression [see WARNINGS ]
- Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see WARNINGS ]
- Known or suspected gastrointestinal obstruction, including paralytic ileus [see WARNINGS ]
Hypersensitivity to oxycodone, acetaminophen, or any other component of the product (e.g., anaphylaxis) [see WARNINGS , ADVERSE REACTIONS ]
ADVERSE REACTIONS
The following adverse reactions have been identified during post approval use of oxycodone hydrochloride and acetaminophen oral solution. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Serious adverse reactions that may be associated with oxycodone hydrochloride and acetaminophen oral solution use include respiratory depression, apnea, respiratory arrest, circulatory depression, hypotension, and shock [see OVERDOSAGE ].
The most frequently observed non-serious adverse reactions include lightheadedness, dizziness, drowsiness or sedation, nausea, and vomiting. These effects seem to be more prominent in ambulatory than in nonambulatory patients, and some of these adverse reactions may be alleviated if the patient lies down. Other adverse reactions include euphoria, dysphoria, constipation, and pruritus.
Hypersensitivity reactions may include: Skin eruptions, urticarial, erythematous skin reactions. Hematologic reactions may include: thrombocytopenia, neutropenia, pancytopenia, hemolytic anemia. Rare cases of agranulocytosis have likewise been associated with acetaminophen use. In high doses, the most serious adverse effect is a dose-dependent, potentially fatal hepatic necrosis. Renal tubular necrosis and hypoglycemic coma also may occur.
Other adverse reactions obtained from postmarketing experiences with oxycodone and acetaminophen are listed by organ system and in decreasing order of severity and/or frequency as follows:
Body as a Whole: Anaphylactoid reaction, allergic reaction, malaise, asthenia, fatigue, chest pain, fever, hypothermia, thirst, headache, increased sweating, accidental overdose, non-accidental overdose
Cardiovascular: Hypotension, hypertension, tachycardia, orthostatic hypotension, bradycardia, palpitations, dysrhythmias
Central and Peripheral Nervous System: Stupor, tremor, paraesthesia, hypoaesthesia, lethargy, seizures, anxiety, mental impairment, agitation, cerebral edema, confusion, dizziness
Fluid and Electrolyte: Dehydration, hyperkalemia, metabolic acidosis, respiratory alkalosis
Gastrointestinal: Dyspepsia, taste disturbances, abdominal pain, abdominal distention, sweating increased, diarrhea, dry mouth, flatulence, gastrointestinal disorder, nausea, vomiting, pancreatitis, intestinal obstruction, ileus
Hepatic: Transient elevations of hepatic enzymes, increase in bilirubin, hepatitis, hepatic failure, jaundice, hepatotoxicity, hepatic disorder
Hearing and Vestibular: Hearing loss, tinnitus
Hematologic: Thrombocytopenia
Hypersensitivity: Acute anaphylaxis, angioedema, asthma, bronchospasm, laryngeal edema, urticaria, anaphylactoid reaction
Metabolic and Nutritional: Hypoglycemia, hyperglycemia, acidosis, alkalosis
Musculoskeletal: Myalgia, rhabdomyolysis
Ocular: Miosis, visual disturbances, red eye
Psychiatric: Drug dependence, drug abuse, insomnia, confusion, anxiety, agitation, depressed level of consciousness, nervousness, hallucination, somnolence, depression, suicide
Respiratory System: Bronchospasm, dyspnea, hyperpnea, pulmonary edema, tachypnea, aspiration, hypoventilation, laryngeal edema
Skin and Appendages: Erythema, urticaria, rash, flushing
Urogenital: Interstitial nephritis, papillary necrosis, proteinuria, renal insufficiency and failure, urinary retention
- 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 and acetaminophen oral solution.
- Androgen deficienc y: Cases of androgen deficiency have occurred with use of opioids for an extended period of time [see CLINICAL PHARMACOLOGY ].
- Hyperalgesia and Allodynia : Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see WARNINGS ]. Hypoglycemia : Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g., diabetes).
Drug Interactions
Inhibitors of CYP3A4 and CYP2D6
The concomitant use of oxycodone hydrochloride and acetaminophen oral solution and CYP3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), and protease inhibitors (e.g., ritonavir), 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 and acetaminophen oral solution and CYP3A4 and CYP2D6 inhibitors, particularly when an inhibitor is added after a stable dose of oxycodone hydrochloride and acetaminophen oral solution is achieved [see WARNINGS ].
After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the oxycodone plasma concentration will decrease [see CLINICAL PHARMACOLOGY ], resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to oxycodone hydrochloride and acetaminophen oral solution.
If concomitant use is necessary, consider dosage reduction of oxycodone hydrochloride and acetaminophen oral solution until stable drug effects are achieved. Evaluate patients at frequent intervals for respiratory depression and sedation. If a CYP3A4 inhibitor is discontinued, consider increasing the oxycodone hydrochloride and acetaminophen oral solution dosage until stable drug effects are achieved. Evaluate for signs of opioid withdrawal.
Inducers of CYP3A4
The concomitant use of oxycodone hydrochloride and acetaminophen oral solution and CYP3A4 inducers, such as rifampin, carbamazepine, and phenytoin, can decrease the plasma concentration of oxycodone [see CLINICAL PHARMACOLOGY ], resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to oxycodone hydrochloride and acetaminophen oral solution [see WARNINGS ].
After stopping a CYP3A4 inducer, as the effects of the inducer decline, the oxycodone plasma concentration will increase [see CLINICAL PHARMACOLOGY ], which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression.
If concomitant use is necessary, consider increasing the oxycodone hydrochloride and acetaminophen oral solution dosage until stable drug effects are achieved. Evaluate for signs of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider oxycodone hydrochloride and acetaminophen oral solution dosage reduction and evaluate patients at frequest intervals for signs of respiratory depression and sedation.
Benzodiazepines and Other Central Nervous System (CNS) Depressants
Due to additive pharmacologic effect, the concomitant use of benzodiazepines and other CNS depressants such as benzodiazepines and other sedative hypnotics, anxiolytics, and tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.
Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Inform patients and caregivers of this potential interaction, educate them on the signs and symptoms of respiratory depression (including sedation). If concomitant use is warranted, consider prescribing naloxone for the emergency treatment of opioid overdose [see WARNINGS ].
Serotonergic Drugs
The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tryptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), certain muscle relaxants (i.e., cyclobenzaprine, metaxalone), and monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue), has resulted in serotonin syndrome [see PRECAUTIONS; Information for Patients ].
If concomitant use is warranted, frequently evaluate the patient, particularly during treatment initiation and dose adjustment. Discontinue oxycodone hydrochloride and acetaminophen oral solution if serotonin syndrome is suspected.
Monoamine Oxidase Inhibitors (MAOIs)
The concomitant use of opioids and MAOIs, such as phenelzine, tranylcypromine, linezolid, may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see WARNINGS ].
The use of oxycodone hydrochloride and acetaminophen 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.
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics
The concomitant use of opioids with other opioid analgesics, such as butorphanol, nalbuphine, pentazocine, may reduce the analgesic effect of oxycodone hydrochloride and acetaminophen oral solution and/or precipitate withdrawal symptoms.
Advise patient to avoid concomitant use of these drugs.
Muscle Relaxants
Oxycodone hydrochloride and acetaminophen oral solution may enhance the neuromuscular-blocking action of skeletal muscle relaxants and produce an increase in the degree of respiratory depression.
Because respiratory depression that may be greater than otherwise expected, decrease the dosage of oxycodone hydrochloride and acetaminophen oral solution and/or the muscle relaxant as necessary.
Due to the risk of respiratory depression with concomitant use of muscle relaxants and opioids, consider prescribing naloxone for the emergency treatment of opioid overdose [see WARNINGS ].
Diuretics
Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Evaluate patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.
Anticholinergic Drugs
The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Evaluate patients for signs of urinary retention or reduced gastric motility when oxycodone hydrochloride and acetaminophen oral solution is used concomitantly with anticholinergic drugs.
Alcohol, ethyl
Hepatotoxicity has occurred in chronic alcoholics following various dose levels (moderate to excessive) of acetaminophen.
Oral Contraceptives
Increase in glucuronidation resulting in increased plasma clearance and a decreased half-life of acetaminophen.
Charcoal (activated)
Reduces acetaminophen absorption when administered as soon as possible after overdose.
Beta Blockers (Propranolol)
Propranolol appears to inhibit the enzyme systems responsible for the glucuronidation and oxidation of acetaminophen. Therefore, the pharmacologic effects of acetaminophen may be increased.
Loop Diuretics
The effects of the loop diuretic may be decreased because acetaminophen may decrease renal prostaglandin excretion and decrease plasma renin activity.
Lamotrigine
Serum lamotrigine concentrations may be reduced, producing a decrease in therapeutic effects.
Probenecid
Probenecid may increase the therapeutic effectiveness of acetaminophen slightly.
Zidovudine
The pharmacologic effects of zidovudine may be decreased because of enhanced non-hepatic or renal clearance of zidovudine
DESCRIPTION
Oxycodone hydrochloride and acetaminophen are available in liquid form for oral administration.
Each 5 mL of oral solution for oral administration contains:
Oxycodone hydrochloride USP................................................ 10 mg•
(•10 mg oxycodone hydrochloride is equivalent to 8.9637 mg oxycodone)
Acetaminophen USP................................................................. 300 mg
Inactive Ingredients
The solution contains: anhydrous citric acid, edetate disodium, fructose, glycerin, polyethylene glycol, potassium sorbate, propylene glycol, purified water, saccharin sodium with FD&C Red #40 as coloring and tropical fruit punch flavoring.
Oxycodone hydrochloride and acetaminophen oral solution contains oxycodone, 14-hydroxydihydrocodeinone, a semisynthetic opioid analgesic which occurs as a white to off-white fine crystalline powder. The molecular formula for oxycodone hydrochloride is C 18 H 21 NO 4 ∙ HCl and the molecular weight is 351.82. It is derived from the opium alkaloid, thebaine, and may be represented by the following structural formula:
Oxycodone hydrochloride and acetaminophen oral solution contains acetaminophen, 4'-hydroxyacetanilide, is a non-opiate, non-salicylate analgesic and antipyretic which occurs as a white, odorless, crystalline powder. The molecular formula for acetaminophen is C 8 H 9 NO 2 and the molecular weight is 151.17. It may be represented by the following structural formula
CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY
Mechanism of Action
Oxycodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, although it can interact with 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.
The precise mechanism of the analgesic properties of acetaminophen is not established but is thought to involve central actions.
Pharmacodynamics
Effects on the Central Nervous System
Oxycodone produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation.
Oxycodone causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations.
Therapeutic doses of acetaminophen have negligible effects on the cardiovascular or respiratory systems; however, toxic doses may cause circulatory failure and rapid, shallow breathing.
Effects on the Gastrointestinal Tract and Other Smooth Muscle
Oxycodone causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase.
Effects on the Cardiovascular System
Oxycodone produces peripheral vasodilation which may result in orthostatic hypotension or syncope. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension.
Effects on the Endocrine System
Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see ADVERSE REACTIONS ]. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon.
Use of opioids for an extended period of time may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as symptoms as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. The causal role of opioids in the syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date [see ADVERSE REACTIONS ].
Effects on the Immune System
Opioids have been shown to have a variety of effects on components of the immune system. The clinical significance of these findings is unknown. Overall, the effects of opioids appear to be modestly immunosuppressive.
Concentration–Efficacy Relationships
The minimum effective analgesic concentration will vary widely among patients, especially among patients who have been previously treated with opioid agonists. The minimum effective analgesic concentration of oxycodone for any individual patient may increase over time due to an increase in pain, the development of a new pain syndrome, and/or the development of analgesic tolerance [see DOSAGE AND ADMINISTRATION ].
Concentration–Adverse Reaction Relationships
There is a relationship between increasing oxycodone plasma concentration and increasing frequency of dose-related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression. In opioid-tolerant patients, the situation may be altered by the development of tolerance to opioid-related adverse reactions [see DOSAGE AND ADMINISTRATION ].
Pharmacokinetics
Absorption and Distribution
The mean absolute oral bioavailability of oxycodone in cancer patients was reported to be about 87%. Oxycodone has been shown to be 45% bound to human plasma proteins in vitro . The volume of distribution after intravenous administration is 211.9 ±186.6 L.
Absorption of acetaminophen is rapid and almost complete from the GI tract after oral administration. With overdosage, absorption is complete in 4 hours. Acetaminophen is relatively uniformly distributed throughout most body fluids. Binding of the drug to plasma proteins is variable; only 20% to 50% may be bound at the concentrations encountered during acute intoxication.
Metabolism and Elimination
Oxycodone
In humans, oxycodone is extensively metabolized to noroxycodone by means of CYP3A-mediated N-demethylation, oxymorphone by means of CYP2D6-mediated O-demethylation, and their glucuronides [see PRECAUTIONS; Drug Interactions ].
Acetaminophen
Acetaminophen is rapidly absorbed from the gastrointestinal tract and is distributed throughout most body tissues. A small fraction (10-25%) of acetaminophen is bound to plasma proteins. The plasma half-life is 1.25 to 3 hours, but may be increased by liver damage and following overdosage. Elimination of acetaminophen is principally by liver metabolism (conjugation) and subsequent renal excretion of metabolites. Acetaminophen is primarily metabolized in the liver by first-order kinetics and involves three principal separate pathways: conjugation with glucuronide; conjugation with sulfate; and oxidation via the cytochrome, P450-dependent, mixed-function oxidase enzyme pathway to form a reactive intermediate metabolite, which conjugates with glutathione and is then further metabolized to form cysteine and mercapturic acid conjugates. The principal cytochrome P450 isoenzyme involved appears to be CYP2E1, with CYP1A2 and CYP3A4 as additional pathways. Approximately 85% of an oral dose appears in the urine within 24 hours of administration, most as the glucuronide conjugate, with small amounts of other conjugates and unchanged drug [see OVERDOSAGE ] for toxicity information.
HOW SUPPLIED
Oxycodone hydrochloride and acetaminophen oral solution, each 5 mL (teaspoonful) of which contains oxycodone hydrochloride 10 mg and acetaminophen 300 mg, is supplied as a red, tropical fruit punch flavored liquid in 120 mL bottles, NDC 72887-648-12.
Storage
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container with a child-resistant closure.
Store oxycodone hydrochloride and acetaminophen oral solution securely and dispose of properly [see PRECAUTIONS; Information for Patients/Caregivers ].
Distributed by:
FH2 Pharma LLC
Las Vegas, NV 89148
Mechanism of Action
Oxycodone is a full opioid agonist with relative selectivity for the mu-opioid receptor, although it can interact with 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.
The precise mechanism of the analgesic properties of acetaminophen is not established but is thought to involve central actions.
