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hydrocodone bitartrate and acetaminophen
Mechanism of Action Hydrocodone is full opioid agonist with relative selectivity for the mu-opioid (μ) receptor, although it can interact with other opioid receptors at higher doses. The principal therapeutic action of hydrocodone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with hydrocodone. 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.
At a glance
| Generic name | hydrocodone bitartrate and acetaminophen |
|---|---|
| Also known as | Norco |
| Sponsor | Rush University Medical Center |
| Modality | Small molecule |
| Therapeutic area | Neuroscience |
| Phase | discontinued |
Mechanism of action
INDICATIONS AND USAGE Hydrocodone Bitartrate and Acetaminophen Tablets, USP are indicated for the management of moderate to moderately severe 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, even at recommended doses [see WARNINGS ], reserve Hydrocodone Bitartrate and Acetaminophen Tablets, USP 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
Approved indications
Boxed warnings
- WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and CYTOCHROME P450 3A4 INTERACTION; HEPATOTOXICITY; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Addiction, Abuse, and Misuse Hydrocodone Bitartrate and Acetaminophen Tablets, USP, expose 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 Hydrocodone Bitartrate and Acetaminophen Tablets, USP, and monitor all patients regularly for the development of these behaviors and conditions [see WARNINGS]. Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS): To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products [see Warnings] . 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 • complete a REMS-compliant education program, • 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. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of Hydrocodone Bitartrate and Acetaminophen Tablets, USP. Monitor for respiratory depression, especially during initiation of Hydrocodone Bitartrate and Acetaminophen Tablets, USP or following a dose increase [see WARNINGS]. Accidental Ingestion Accidental ingestion of Hydrocodone Bitartrate and Acetaminophen Tablets, USP, especially by children, can result in a fatal overdose of Hydrocodone Bitartrate and Acetaminophen Tablets, USP [see WARNINGS]. Neonatal Opioid Withdrawal Syndrome Prolonged use of Hydrocodone Bitartrate and Acetaminophen Tablets, USP 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 [see WARNINGS]. Cytochrome P450 3A4 Interaction The concomitant use of Hydrocodone Bitartrate and Acetaminophen Tablets, USP with all Cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone 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 hydrocodone plasma concentrations. Monitor patients receiving Hydrocodone Bitartrate and Acetaminophen Tablets, USP and any Cytochrome P450 3A4 inhibitor or inducer for signs of respiratory depression or sedation [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 4,000 milligrams per day, and often involve more than one acetaminophen-containing product [see WARNINGS, OVERDOSAGE]. 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 sedat
Common side effects
Drug interactions
- Drug Interactions Inhibitors of CYP3A4 and CYP2D6 The concomitant use of Hydrocodone Bitartrate and Acetaminophen Tablets 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 hydrocodone from Hydrocodone Bitartrate and Acetaminophen Tablets, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of Hydrocodone Bitartrate and Acetaminophen Tablets and both CYP3A4 and CYP2D6 inhibitors, particularly when an inhibitor is added after a stable dose of Hydrocodone Bitartrate and Acetaminophen Tablets is achieved [see WARNINGS ] . After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the hydrocodone plasma concentration will decrease [see CLINICAL PHARMACOLOGY ], resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to Hydrocodone Bitartrate and Acetaminophen Tablets. If concomitant use is necessary, consider dosage reduction of Hydrocodone Bitartrate and Acetaminophen Tablets until stable drug effects are achieved. Follow patients for respiratory depression and sedation at frequent intervals. If a CYP3A4 inhibitor is discontinued, consider increasing the Hydrocodone Bitartrate and Acetaminophen Tablets dosage until stable drug effects are achieved . Follow for signs or symptoms of opioid withdrawal. Inducers of CYP3A4 The concomitant use of Hydrocodone Bitartrate and Acetaminophen Tablets and CYP3A4 inducers, such as rifampin, carbamazepine, and phenytoin, can decrease the plasma concentration of hydrocodone [see CLINICAL PHARMACOLOGY ], resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to hydrocodone [see WARNINGS ] . After stopping a CYP3A4 inducer, as the effects of the inducer decline, the hydrocodone 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 Hydrocodone Bitartrate and Acetaminophen Tablets dosage until stable drug effects are achieved [see DOSAGE AND ADMINISTRATION ] . Follow the patient for signs and symptoms of opioid withdrawal. If a CYP3A4 inducer is discontinued, consider Hydrocodone Bitartrate and Acetaminophen Tablets dosage reduction and follow for signs of respiratory depression. Benzodiazepines and Other CNS Depressants Due to additive pharmacologic effect, the concomitant use of benzodiazepines and other CNS depressants, such as benzodiazepines and other sedatives/hypnotics, anxiolytics, 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. Follow patients closely for signs of respiratory depression and sedation [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), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), 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, carefully follow the patient, particularly during t
Key clinical trials
- A Double Blinded, Placebo-controlled Randomized Control Trial Comparing Intravenous Moderate Sedation and Oral/Sublingual Analgesia/Anxiolysis for First Trimester Surgical Abortions (Phase 4)
- Pain Management in Head and Neck Surgery Patients (Phase 4)
- A Randomized, Multicenter, Single-blind, Placebo-controlled Study Comparing the Analgesic Efficacy and Safety of Hydrocodone/ Acetaminophen Extended-release Tablets and Hydrocodone/Acetaminophen (NORC (Phase 2)
- A Randomized, Open-Label, Single-Dose Bioavailability Study of SPARC001in Healthy, Adult Volunteers Under Fed and Fasted Conditions" (Phase 1)
- A Relative Bioavailability Trial to Investigate the Pharmacokinetics of Two Immediate Release Fixed Dose Combinations of Hydrocodone Bitartrate and Acetaminophen (a New Abuse Deterrent Tablet and a Ma (Phase 1)
- Nitrous Oxide for Pain Management During In-office Transcervical Sterilization (NA)
- Use of Enhanced Recovery After Surgery (ERAS) in Minimizing Opioid Use for Patients Undergoing Thyroidectomy (NA)
- A Double-Blind, Randomized, Placebo-Controlled, Multiple-dose Multi-Center Phase III Study of the Safety and Efficacy of Cl-108 in the Treatment of Moderate to Severe Pain (Phase 3)
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
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