325 5 norco: Hydrocodone And Acetaminophen (Oral Route) Proper Use
Hydrocodone and Acetaminophen – StatPearls
Continuing Education Activity
Hydrocodone is one of the most common pain medications prescribed by clinicians and one of the most abused by patients. It is a relatively potent drug for moderate-to-severe pain control in postoperative patients, patients with trauma, or patients with cancer. The combination of hydrocodone with acetaminophen is much more efficacious in several randomized studies without any significant changes in adverse effects. Moreover, hydrocodone/acetaminophen has common use as an antitussive agent. This activity outlines the indications, mechanism of action, methods of administration, significant adverse effects, contraindications, monitoring, and toxicity of hydrocodone/acetaminophen so that providers can direct patient therapy to optimal outcomes.
Objectives:
Identify the mechanism of action of hydrocodone/acetaminophen.
Outline the approved uses for initiating hydrocodone/acetaminophen therapy.
Summarize the adverse event profile and contraindications to using hydrocodone/acetaminophen.
Explain interprofessional team strategies for improving care coordination and communication to advance hydrocodone/acetaminophen therapy, improve outcomes, and minimize adverse events and misuse, especially in light of the ongoing opioid crisis.
Access free multiple choice questions on this topic.
Indications
Hydrocodone is one of the most common pain medications prescribed by clinicians and one of the most abused by patients. It is a relatively potent drug for moderate-to-severe pain control in postoperative patients, patients with trauma, and patients with cancer. The combination of hydrocodone with acetaminophen is much more efficacious than placebo in several randomized studies without any significant changes in adverse effects.[1] Moreover, hydrocodone/acetaminophen has common use as an antitussive agent.[2]
Mechanism of Action
Hydrocodone is a full opioid agonist that interacts with the mu-receptors and, to a lesser extent, with delta receptors in the body.
[3] Activated mu-opioid receptors lead to inhibition of nociceptive pain reflexes and induce profound analgesia without affecting other sensory modalities such as touch. Additionally, activated opioid receptors inhibit neurotransmitter release, including substance P.[3] Hydrocodone reaches maximum serum concentrations within 1 hour with an elimination half-life of 4 to 6 hours.[4] Hydrocodone has to be metabolized by CYP2D6 to its active form, hydromorphone.[3]
Acetaminophen’s mechanism of action of analgesia is not fully understood. The hypothesis has been that it results from COX inhibition and activation of descending serotonergic inhibitory pathways in the CNS. Antipyretic effects occur via inhibition of the hypothalamic heat-regulating center. Acetaminophen is readily absorbed from the gastrointestinal tract. Plasma protein binding of acetaminophen is about 10 to 25%. The plasma half-life ranges from 1 to 3 hours; however, it may increase due to liver damage following overdose.
Approximately 85% of the drug is eliminated in the urine within 24 hours of administration.[5]
Administration
Hydrocodone and acetaminophen combination is available as oral tablet and oral solution formulation.
Hydrocodone bitartrate 5 mg / acetaminophen 300 mg
Hydrocodone bitartrate 5 mg / acetaminophen 325 mg
Hydrocodone bitartrate 7.5 mg / acetaminophen 300 mg
Hydrocodone bitartrate 7.5 mg / acetaminophen 325 mg
Hydrocodone bitartrate 10 mg / acetaminophen 300 mg
Hydrocodone bitartrate 10 mg / acetaminophen 325 mg
Hydrocodone bitartrate 7.5 mg / acetaminophen 325 mg per 15 mL oral solution
Dosing Regimen for Pain Management
The lowest dose necessary for adequate analgesia is recommended and should be titrated individually for each patient taking into account the severity of pain, response, and prior analgesic experience.
For initial oral tablets therapy, the usual adult dose of hydrocodone and acetaminophen ( 5 mg / 300 mg) is one or two tablets every four to six hours as needed for pain.
The total daily dosage should not be more than eight tablets.For initial oral solution therapy, the usual adult dose of solution ( 7.5mg / 325mg per 15 mL) is one tablespoonful (15 mL) every 4 to 6 hours as needed for pain. The total daily dosage for adults should not be more than six tablespoonfuls.
For the conversion from other opioids to hydrocodone and acetaminophen therapy, it is recommended to underestimate the dose of hydrocodone bitartrate and acetaminophen on 24 hours basis for managing an adverse reaction due to the risk of overdose. The relative bioavailability information is unknown for conversion from extended-release hydrocodone to hydrocodone and acetaminophen therapy. So close monitoring for signs of excessive sedation and respiratory depression is recommended. The dose should be titrated on an individual basis. Continuous reevaluation of the dose of hydrocodone and acetaminophen is needed to maintain adequate pain control, minimize adverse effects, and monitor the development of addiction, abuse, or misuse.
For patients who may have a physical dependence on opioids, abrupt discontinuation of hydrocodone and acetaminophen therapy may result in severe withdrawal symptoms, uncontrolled pain, and suicidal tendency.
The total daily dosage should not be more than eight tablets.
Specific Patients Population
Patient with Hepatic Impairment: There is no dose adjustment guidance in the manufacturer label for patients with hepatic impairment. However, initiating therapy with the lowest dose with continuous monitoring is recommended in these patients.
Patient with Renal Impairment: There is no dose adjustment guidance in the manufacturer label for patients with renal impairment. However, 26% of hydrocodone and 85% of acetaminophen are eliminated in the urine, so the drug should be used with caution.
Pregnant Women: It is considered as pregnancy category C medicine. There is a US box warning related to pregnancy. During pregnancy, prolonged use of hydrocodone and acetaminophen can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized early and treated accordingly.
Breastfeeding Women: Hydrocodone and Acetaminophen are present in breast milk. The decision to continue or discontinue breastfeeding during therapy should be based on the risk of infant exposure versus the benefits of breastfeeding and treatment to the mother.[6][7]
Pediatric Patients: The dose of hydrocodone for pediatric patients is titrated based on desired analgesic effect. While considering acetaminophen dose, it is recommended to consider the maximum daily dose of acetaminophen from all other sources like OTC, other prescription, or combination products. The maximum daily dose should not exceed 2000 mg for acetaminophen to minimize hepatotoxicity maximum. Based on the information provided in the hydrocodone and acetaminophen oral solution label, dosing should be calculated as 0.27 mL/kg child weight (equivalent to 0.135 mg/kg hydrocodone and 5.85 mg/kg dose of acetaminophen) whenever possible.
Geriatric Patients: For safety and efficacy, it is recommended to start the initial dose at the lower end of the dosing range in geriatric patients and monitor patients closely.
Adverse Effects
Opioid-induced constipation, dizziness, nausea, vomiting, drowsiness, and respiratory depression are common adverse reactions of hydrocodone-acetaminophen medication. There have been reports of progressive sensorineural hearing loss with chronic hydrocodone/acetaminophen use that is not responsive to high-dose steroids but responsive to cochlear implantation.[2]
As with all opioids, tolerance leading to ever-increasing doses of opioids to maintain the same level of pain control and physical dependence is the most common side effect. Moreover, acute and chronic opioid administration can inhibit antibody and cellular immune responses, natural killer cell activity, cytokine expression, and phagocytic activity. As a result, there are implications of opioids, pointing to an increased incidence of infections in subjects with heroin use disorder.
Opioid users also suffer from endocrine changes in the body, including but not limited to sexual dysfunction, depression, and decreased energy levels, resulting from hypogonadotropic hypogonadism.
Also, opioid-induced hyperalgesia is a recently recognized phenomenon after patients experienced increasing pain despite increasing doses of opioids.[2]
Other Adverse Reactions
Central Nervous System: Lethargy, mental clouding, impairment of the physical and mental performance, fear, anxiety, dysphoria, mood changes, dependence
Genitourinary System: Ureteral spasm, urinary retention, spasm of vesical sphincters reported with opiates
Dermatological: Pruritus and skin rash
Contraindications
Contraindications to hydrocodone/acetaminophen include patients with severe respiratory depression, acute or significant bronchial asthma, gastrointestinal obstruction, and anaphylactic reactions due to components of the formula.
As per the manufacturer’s label, several drugs interact with hydrocodone/acetaminophen and caution should be used when they are coadministered.[8][9]
CYP3A4 and CYP2D6 Inhibitors: The coadministration of hydrocodone and acetaminophen with CYP3A4 inhibitors (erythromycin, ketoconazole, and ritonavir) may lead to an increase in the plasma concentration of the hydrocodone and this may result in increased or prolonged opioid effects.
These effects may be more pronounced when CYP3A4 and CYP2D6 inhibitors are coadministered with hydrocodone and acetaminophen.CYP3A4 Inducers: The coadministration of hydrocodone and acetaminophen with CYP3A4 inducers (rifampin, carbamazepine, and phenytoin) may lead to a decrease in the plasma concentration of hydrocodone, and this may result in decreased efficacy.
Benzodiazepines or Other CNS Depressants: The coadministration of hydrocodone and acetaminophen with benzodiazepines or other CNS depressants, due to its additive pharmacologic effect, may lead to an increase in the risk of hypotension, respiratory depression, severe sedation, coma, and death.
Serotonergic Drugs: The coadministration of hydrocodone and acetaminophen with other drugs that affect the serotonergic neurotransmitter system (selective serotonin reuptake inhibitors, serotonin, and norepinephrine reuptake inhibitors, tricyclic antidepressants, triptans, 5-HT3 receptor antagonists) or with drugs that affect the serotonin neurotransmitter system (mirtazapine, trazodone, tramadol cyclobenzaprine, metaxalone, monoamine oxidase inhibitors) may result in serotonin syndrome.
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics: The coadministration of hydrocodone and acetaminophen with other opioid analgesics (butorphanol, nalbuphine, pentazocine) may lead to reducing the analgesic effect of opioids and/or precipitate withdrawal symptoms.
Muscle Relaxants: The coadministration of hydrocodone and acetaminophen with muscle relaxants may enhance the neuromuscular blocking action and may induce a higher degree of respiratory depression.
Diuretics: The coadministration of hydrocodone and acetaminophen with other diuretics may reduce the efficacy of diuretics due to the induction of antidiuretic hormone.
Anticholinergic Drugs: The coadministration of hydrocodone and acetaminophen with anticholinergic drugs may increase the risk of urinary retention and/or severe constipation.
These effects may be more pronounced when CYP3A4 and CYP2D6 inhibitors are coadministered with hydrocodone and acetaminophen.
Monitoring
Pain relief and adverse events should undergo frequent assessments.
The dosing should start low and slow and titrated up as necessary to obtain adequate analgesia while having minimal side effects.
Hydrocodone is a DEA Schedule II controlled substance and since it has a potential for abuse, misuse, and use disorder. Consequently, it is vital to monitor patients for addiction, abuse, and misuse signs. In addition, patients with a prior history of drug addiction or mental illness have a higher risk of addiction.
For toxicity monitoring, obtain serial liver function tests in patients with severe hepatic disease. Also, monitor serial renal function in elderly patients and patients with severe renal disease.
The clinicians should monitor the following physical findings for the signs of toxicity.
Signs of confusion and over-sedation in the elderly
Addiction, abuse, or misuse behaviors and conditions during treatment
Signs of respiratory depression, especially within 24 to 72 hours of treatment initiation and after dose increases
Signs and symptoms of respiratory depression and sedation in patients susceptible to the intracranial effects of carbon dioxide retention
Severe hypotension at the start of treatment and dose modification
In patients with a history of seizure disorders, monitor for worsened seizure control
Toxicity
Acetaminophen has been associated with fatal hepatic necrosis if taken at doses more than 4 g per day, especially with the ingestion of another acetaminophen-containing product.
Furthermore, large doses may cause difficulty with breathing. In overdose, activated charcoal should be the first attempted intervention before N-acetylcysteine (NAC). For patients presenting for 4 hours or later, the serum acetaminophen level should be obtained promptly.
Hydrocodone intake may lead to life-threatening respiratory depression, especially if taken together with benzodiazepines or other CNS depressants. In case of overdose, the first step is to protect the airways and place the patient on invasive ventilation assistance, if needed. The opioid antagonists, nalmefene or naloxone, are specific antidotes for respiratory depression. Opioid antagonists should be avoided in the absence of clinically significant respiratory or circulatory depression. In addition, there is a high risk of precipitating acute opioid withdrawal in an individual who is physically dependent on opioids.
Enhancing Healthcare Team Outcomes
It is not surprising that, without proper barriers and monitoring for the detrimental effects of hydrocodone and acetaminophen intoxication, the morbidity and mortality of using opioid analgesia can be quite substantial.
The drug information sheet from the manufacturer emphasizes in bold letters the importance of warning patients of abuse, misuse, and addiction of hydrocodone and acetaminophen, which can lead to overdose and death. Multiple efforts point toward reducing prescription abuse and misuse.
The mitigation of opioid overdose and misuse risk starts from the system-level intervention by clinicians and nurses prescribing narcotics. In addition, the Prescription Drug Monitoring Program and Medicaid managed care lock-in program require that patients receive all scripts from a single prescriber. Although over 55% dropped from the program, the proportion of stable patients, i.e., patients exclusively filled from one prescriber, increased from 31% to 78% at 36 months.[10] [Level 4]
Pharmacists should use formulary management tools to address both opioid overprescribing and overdose. One of them is a prior authorization requirement placed by the insurance companies to verify that the medication is necessary.
Cochran et al. conducted a retrospective cohort study evaluating the effects of prior authorization on the rate of abuse and overdose of patients enrolled in the Pennsylvania Medicaid program from 2010 to 2012. The study demonstrated that plans with prior authorization requirements had lower rates of use disorder and overdose.[11] [Level 4]
All in all, there is a battle to reduce the opioid prescription crisis, and still, rates of overdose continue. Numerous interventions show some promise in mitigating this problem, and it truly takes an interprofessional team, including clinicians, mid-level practitioners, nurses, and pharmacists, to achieve this goal. [Level 5]
Review Questions
Access free multiple choice questions on this topic.
Comment on this article.
References
- 1.
Vardy J, Agar M. Nonopioid drugs in the treatment of cancer pain. J Clin Oncol. 2014 Jun 01;32(16):1677-90. [PubMed: 24799483]
- 2.
Benyamin R, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N, Glaser SE, Vallejo R. Opioid complications and side effects. Pain Physician. 2008 Mar;11(2 Suppl):S105-20. [PubMed: 18443635]
- 3.
Sarhill N, Walsh D, Nelson KA. Hydromorphone: pharmacology and clinical applications in cancer patients. Support Care Cancer. 2001 Mar;9(2):84-96. [PubMed: 11305075]
- 4.
Smith HS. The metabolism of opioid agents and the clinical impact of their active metabolites. Clin J Pain. 2011 Nov-Dec;27(9):824-38. [PubMed: 21677572]
- 5.
Jóźwiak-Bebenista M, Nowak JZ. Paracetamol: mechanism of action, applications and safety concern. Acta Pol Pharm. 2014 Jan-Feb;71(1):11-23. [PubMed: 24779190]
- 6.
Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Sep 19, 2022. Hydrocodone. [PubMed: 30000284]
- 7.
Drugs and Lactation Database (LactMed®) [Internet].
National Institute of Child Health and Human Development; Bethesda (MD): Mar 21, 2022. Acetaminophen. [PubMed: 30000253]- 8.
Monte AA, Heard KJ, Campbell J, Hamamura D, Weinshilboum RM, Vasiliou V. The effect of CYP2D6 drug-drug interactions on hydrocodone effectiveness. Acad Emerg Med. 2014 Aug;21(8):879-85. [PMC free article: PMC4150819] [PubMed: 25156930]
- 9.
Lee D, Stout P, Egdorf D. Houston Cocktail: Driving under influence of hydrocodone, alprazolam, and carisoprodol. Forensic Sci Int. 2021 Apr 28;323:110819. [PubMed: 33964487]
- 10.
Dreyer TR, Michalski T, Williams BC. Patient Outcomes in a Medicaid Managed Care Lock-In Program. J Manag Care Spec Pharm. 2015 Nov;21(11):1006-12. [PubMed: 26521112]
- 11.
Cochran G, Gordon AJ, Gellad WF, Chang CH, Lo-Ciganic WH, Lobo C, Cole E, Frazier W, Zheng P, Kelley D, Donohue JM. Medicaid prior authorization and opioid medication abuse and overdose. Am J Manag Care.
2017 May 01;23(5):e164-e171. [PMC free article: PMC6719534] [PubMed: 28810127]
National Institute of Child Health and Human Development; Bethesda (MD): Mar 21, 2022. Acetaminophen. [PubMed: 30000253]
2017 May 01;23(5):e164-e171. [PMC free article: PMC6719534] [PubMed: 28810127]Disclosure: Manuchehr Habibi declares no relevant financial relationships with ineligible companies.
Disclosure: Peggy Kim declares no relevant financial relationships with ineligible companies.
Hydrocodone and Acetaminophen – StatPearls
Continuing Education Activity
Hydrocodone is one of the most common pain medications prescribed by clinicians and one of the most abused by patients. It is a relatively potent drug for moderate-to-severe pain control in postoperative patients, patients with trauma, or patients with cancer. The combination of hydrocodone with acetaminophen is much more efficacious in several randomized studies without any significant changes in adverse effects. Moreover, hydrocodone/acetaminophen has common use as an antitussive agent. This activity outlines the indications, mechanism of action, methods of administration, significant adverse effects, contraindications, monitoring, and toxicity of hydrocodone/acetaminophen so that providers can direct patient therapy to optimal outcomes.
Objectives:
Identify the mechanism of action of hydrocodone/acetaminophen.
Outline the approved uses for initiating hydrocodone/acetaminophen therapy.
Summarize the adverse event profile and contraindications to using hydrocodone/acetaminophen.
Explain interprofessional team strategies for improving care coordination and communication to advance hydrocodone/acetaminophen therapy, improve outcomes, and minimize adverse events and misuse, especially in light of the ongoing opioid crisis.
Access free multiple choice questions on this topic.
Indications
Hydrocodone is one of the most common pain medications prescribed by clinicians and one of the most abused by patients. It is a relatively potent drug for moderate-to-severe pain control in postoperative patients, patients with trauma, and patients with cancer. The combination of hydrocodone with acetaminophen is much more efficacious than placebo in several randomized studies without any significant changes in adverse effects.
[1] Moreover, hydrocodone/acetaminophen has common use as an antitussive agent.[2]
Mechanism of Action
Hydrocodone is a full opioid agonist that interacts with the mu-receptors and, to a lesser extent, with delta receptors in the body.[3] Activated mu-opioid receptors lead to inhibition of nociceptive pain reflexes and induce profound analgesia without affecting other sensory modalities such as touch. Additionally, activated opioid receptors inhibit neurotransmitter release, including substance P.[3] Hydrocodone reaches maximum serum concentrations within 1 hour with an elimination half-life of 4 to 6 hours.[4] Hydrocodone has to be metabolized by CYP2D6 to its active form, hydromorphone.[3]
Acetaminophen’s mechanism of action of analgesia is not fully understood. The hypothesis has been that it results from COX inhibition and activation of descending serotonergic inhibitory pathways in the CNS. Antipyretic effects occur via inhibition of the hypothalamic heat-regulating center.
Acetaminophen is readily absorbed from the gastrointestinal tract. Plasma protein binding of acetaminophen is about 10 to 25%. The plasma half-life ranges from 1 to 3 hours; however, it may increase due to liver damage following overdose. Approximately 85% of the drug is eliminated in the urine within 24 hours of administration.[5]
Administration
Hydrocodone and acetaminophen combination is available as oral tablet and oral solution formulation.
Hydrocodone bitartrate 5 mg / acetaminophen 300 mg
Hydrocodone bitartrate 5 mg / acetaminophen 325 mg
Hydrocodone bitartrate 7.5 mg / acetaminophen 300 mg
Hydrocodone bitartrate 7.5 mg / acetaminophen 325 mg
Hydrocodone bitartrate 10 mg / acetaminophen 300 mg
Hydrocodone bitartrate 10 mg / acetaminophen 325 mg
Hydrocodone bitartrate 7.5 mg / acetaminophen 325 mg per 15 mL oral solution
Dosing Regimen for Pain Management
The lowest dose necessary for adequate analgesia is recommended and should be titrated individually for each patient taking into account the severity of pain, response, and prior analgesic experience.
For initial oral tablets therapy, the usual adult dose of hydrocodone and acetaminophen ( 5 mg / 300 mg) is one or two tablets every four to six hours as needed for pain. The total daily dosage should not be more than eight tablets.
For initial oral solution therapy, the usual adult dose of solution ( 7.5mg / 325mg per 15 mL) is one tablespoonful (15 mL) every 4 to 6 hours as needed for pain. The total daily dosage for adults should not be more than six tablespoonfuls.
For the conversion from other opioids to hydrocodone and acetaminophen therapy, it is recommended to underestimate the dose of hydrocodone bitartrate and acetaminophen on 24 hours basis for managing an adverse reaction due to the risk of overdose. The relative bioavailability information is unknown for conversion from extended-release hydrocodone to hydrocodone and acetaminophen therapy. So close monitoring for signs of excessive sedation and respiratory depression is recommended.
The dose should be titrated on an individual basis. Continuous reevaluation of the dose of hydrocodone and acetaminophen is needed to maintain adequate pain control, minimize adverse effects, and monitor the development of addiction, abuse, or misuse.For patients who may have a physical dependence on opioids, abrupt discontinuation of hydrocodone and acetaminophen therapy may result in severe withdrawal symptoms, uncontrolled pain, and suicidal tendency.
The dose should be titrated on an individual basis. Continuous reevaluation of the dose of hydrocodone and acetaminophen is needed to maintain adequate pain control, minimize adverse effects, and monitor the development of addiction, abuse, or misuse.Specific Patients Population
Patient with Hepatic Impairment: There is no dose adjustment guidance in the manufacturer label for patients with hepatic impairment. However, initiating therapy with the lowest dose with continuous monitoring is recommended in these patients.
Patient with Renal Impairment: There is no dose adjustment guidance in the manufacturer label for patients with renal impairment. However, 26% of hydrocodone and 85% of acetaminophen are eliminated in the urine, so the drug should be used with caution.
Pregnant Women: It is considered as pregnancy category C medicine. There is a US box warning related to pregnancy. During pregnancy, prolonged use of hydrocodone and acetaminophen can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized early and treated accordingly.
Breastfeeding Women: Hydrocodone and Acetaminophen are present in breast milk. The decision to continue or discontinue breastfeeding during therapy should be based on the risk of infant exposure versus the benefits of breastfeeding and treatment to the mother.[6][7]
Pediatric Patients: The dose of hydrocodone for pediatric patients is titrated based on desired analgesic effect. While considering acetaminophen dose, it is recommended to consider the maximum daily dose of acetaminophen from all other sources like OTC, other prescription, or combination products. The maximum daily dose should not exceed 2000 mg for acetaminophen to minimize hepatotoxicity maximum.
Based on the information provided in the hydrocodone and acetaminophen oral solution label, dosing should be calculated as 0.27 mL/kg child weight (equivalent to 0.135 mg/kg hydrocodone and 5.85 mg/kg dose of acetaminophen) whenever possible.Geriatric Patients: For safety and efficacy, it is recommended to start the initial dose at the lower end of the dosing range in geriatric patients and monitor patients closely.
Based on the information provided in the hydrocodone and acetaminophen oral solution label, dosing should be calculated as 0.27 mL/kg child weight (equivalent to 0.135 mg/kg hydrocodone and 5.85 mg/kg dose of acetaminophen) whenever possible.Adverse Effects
Opioid-induced constipation, dizziness, nausea, vomiting, drowsiness, and respiratory depression are common adverse reactions of hydrocodone-acetaminophen medication. There have been reports of progressive sensorineural hearing loss with chronic hydrocodone/acetaminophen use that is not responsive to high-dose steroids but responsive to cochlear implantation.[2]
As with all opioids, tolerance leading to ever-increasing doses of opioids to maintain the same level of pain control and physical dependence is the most common side effect.
Moreover, acute and chronic opioid administration can inhibit antibody and cellular immune responses, natural killer cell activity, cytokine expression, and phagocytic activity. As a result, there are implications of opioids, pointing to an increased incidence of infections in subjects with heroin use disorder.
Opioid users also suffer from endocrine changes in the body, including but not limited to sexual dysfunction, depression, and decreased energy levels, resulting from hypogonadotropic hypogonadism. Also, opioid-induced hyperalgesia is a recently recognized phenomenon after patients experienced increasing pain despite increasing doses of opioids.[2]
Other Adverse Reactions
Central Nervous System: Lethargy, mental clouding, impairment of the physical and mental performance, fear, anxiety, dysphoria, mood changes, dependence
Genitourinary System: Ureteral spasm, urinary retention, spasm of vesical sphincters reported with opiates
Dermatological: Pruritus and skin rash
Contraindications
Contraindications to hydrocodone/acetaminophen include patients with severe respiratory depression, acute or significant bronchial asthma, gastrointestinal obstruction, and anaphylactic reactions due to components of the formula.
As per the manufacturer’s label, several drugs interact with hydrocodone/acetaminophen and caution should be used when they are coadministered.[8][9]
CYP3A4 and CYP2D6 Inhibitors: The coadministration of hydrocodone and acetaminophen with CYP3A4 inhibitors (erythromycin, ketoconazole, and ritonavir) may lead to an increase in the plasma concentration of the hydrocodone and this may result in increased or prolonged opioid effects. These effects may be more pronounced when CYP3A4 and CYP2D6 inhibitors are coadministered with hydrocodone and acetaminophen.
CYP3A4 Inducers: The coadministration of hydrocodone and acetaminophen with CYP3A4 inducers (rifampin, carbamazepine, and phenytoin) may lead to a decrease in the plasma concentration of hydrocodone, and this may result in decreased efficacy.
Benzodiazepines or Other CNS Depressants: The coadministration of hydrocodone and acetaminophen with benzodiazepines or other CNS depressants, due to its additive pharmacologic effect, may lead to an increase in the risk of hypotension, respiratory depression, severe sedation, coma, and death.
Serotonergic Drugs: The coadministration of hydrocodone and acetaminophen with other drugs that affect the serotonergic neurotransmitter system (selective serotonin reuptake inhibitors, serotonin, and norepinephrine reuptake inhibitors, tricyclic antidepressants, triptans, 5-HT3 receptor antagonists) or with drugs that affect the serotonin neurotransmitter system (mirtazapine, trazodone, tramadol cyclobenzaprine, metaxalone, monoamine oxidase inhibitors) may result in serotonin syndrome.
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics: The coadministration of hydrocodone and acetaminophen with other opioid analgesics (butorphanol, nalbuphine, pentazocine) may lead to reducing the analgesic effect of opioids and/or precipitate withdrawal symptoms.
Muscle Relaxants: The coadministration of hydrocodone and acetaminophen with muscle relaxants may enhance the neuromuscular blocking action and may induce a higher degree of respiratory depression.
Diuretics: The coadministration of hydrocodone and acetaminophen with other diuretics may reduce the efficacy of diuretics due to the induction of antidiuretic hormone.
Anticholinergic Drugs: The coadministration of hydrocodone and acetaminophen with anticholinergic drugs may increase the risk of urinary retention and/or severe constipation.
Monitoring
Pain relief and adverse events should undergo frequent assessments. The dosing should start low and slow and titrated up as necessary to obtain adequate analgesia while having minimal side effects.
Hydrocodone is a DEA Schedule II controlled substance and since it has a potential for abuse, misuse, and use disorder. Consequently, it is vital to monitor patients for addiction, abuse, and misuse signs. In addition, patients with a prior history of drug addiction or mental illness have a higher risk of addiction.
For toxicity monitoring, obtain serial liver function tests in patients with severe hepatic disease.
Also, monitor serial renal function in elderly patients and patients with severe renal disease.
The clinicians should monitor the following physical findings for the signs of toxicity.
Signs of confusion and over-sedation in the elderly
Addiction, abuse, or misuse behaviors and conditions during treatment
Signs of respiratory depression, especially within 24 to 72 hours of treatment initiation and after dose increases
Signs and symptoms of respiratory depression and sedation in patients susceptible to the intracranial effects of carbon dioxide retention
Severe hypotension at the start of treatment and dose modification
In patients with a history of seizure disorders, monitor for worsened seizure control
Toxicity
Acetaminophen has been associated with fatal hepatic necrosis if taken at doses more than 4 g per day, especially with the ingestion of another acetaminophen-containing product.
Furthermore, large doses may cause difficulty with breathing. In overdose, activated charcoal should be the first attempted intervention before N-acetylcysteine (NAC). For patients presenting for 4 hours or later, the serum acetaminophen level should be obtained promptly.
Hydrocodone intake may lead to life-threatening respiratory depression, especially if taken together with benzodiazepines or other CNS depressants. In case of overdose, the first step is to protect the airways and place the patient on invasive ventilation assistance, if needed. The opioid antagonists, nalmefene or naloxone, are specific antidotes for respiratory depression. Opioid antagonists should be avoided in the absence of clinically significant respiratory or circulatory depression. In addition, there is a high risk of precipitating acute opioid withdrawal in an individual who is physically dependent on opioids.
Enhancing Healthcare Team Outcomes
It is not surprising that, without proper barriers and monitoring for the detrimental effects of hydrocodone and acetaminophen intoxication, the morbidity and mortality of using opioid analgesia can be quite substantial.
The drug information sheet from the manufacturer emphasizes in bold letters the importance of warning patients of abuse, misuse, and addiction of hydrocodone and acetaminophen, which can lead to overdose and death. Multiple efforts point toward reducing prescription abuse and misuse.
The mitigation of opioid overdose and misuse risk starts from the system-level intervention by clinicians and nurses prescribing narcotics. In addition, the Prescription Drug Monitoring Program and Medicaid managed care lock-in program require that patients receive all scripts from a single prescriber. Although over 55% dropped from the program, the proportion of stable patients, i.e., patients exclusively filled from one prescriber, increased from 31% to 78% at 36 months.[10] [Level 4]
Pharmacists should use formulary management tools to address both opioid overprescribing and overdose. One of them is a prior authorization requirement placed by the insurance companies to verify that the medication is necessary.
Cochran et al. conducted a retrospective cohort study evaluating the effects of prior authorization on the rate of abuse and overdose of patients enrolled in the Pennsylvania Medicaid program from 2010 to 2012. The study demonstrated that plans with prior authorization requirements had lower rates of use disorder and overdose.[11] [Level 4]
All in all, there is a battle to reduce the opioid prescription crisis, and still, rates of overdose continue. Numerous interventions show some promise in mitigating this problem, and it truly takes an interprofessional team, including clinicians, mid-level practitioners, nurses, and pharmacists, to achieve this goal. [Level 5]
Review Questions
Access free multiple choice questions on this topic.
Comment on this article.
References
- 1.
Vardy J, Agar M. Nonopioid drugs in the treatment of cancer pain. J Clin Oncol. 2014 Jun 01;32(16):1677-90. [PubMed: 24799483]
- 2.
Benyamin R, Trescot AM, Datta S, Buenaventura R, Adlaka R, Sehgal N, Glaser SE, Vallejo R. Opioid complications and side effects. Pain Physician. 2008 Mar;11(2 Suppl):S105-20. [PubMed: 18443635]
- 3.
Sarhill N, Walsh D, Nelson KA. Hydromorphone: pharmacology and clinical applications in cancer patients. Support Care Cancer. 2001 Mar;9(2):84-96. [PubMed: 11305075]
- 4.
Smith HS. The metabolism of opioid agents and the clinical impact of their active metabolites. Clin J Pain. 2011 Nov-Dec;27(9):824-38. [PubMed: 21677572]
- 5.
Jóźwiak-Bebenista M, Nowak JZ. Paracetamol: mechanism of action, applications and safety concern. Acta Pol Pharm. 2014 Jan-Feb;71(1):11-23. [PubMed: 24779190]
- 6.
Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Sep 19, 2022. Hydrocodone. [PubMed: 30000284]
- 7.
Drugs and Lactation Database (LactMed®) [Internet].
National Institute of Child Health and Human Development; Bethesda (MD): Mar 21, 2022. Acetaminophen. [PubMed: 30000253]- 8.
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2017 May 01;23(5):e164-e171. [PMC free article: PMC6719534] [PubMed: 28810127]Disclosure: Manuchehr Habibi declares no relevant financial relationships with ineligible companies.
Disclosure: Peggy Kim declares no relevant financial relationships with ineligible companies.
Percocet vs Norco: Differences, Similarities & What’s Best for You – Drug Vs. Friend
Home >> Drug Vs. Friend >> Percocet vs Norco: Differences, Similarities & Which is Best for You
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Drug Overview and Key Differences | Conditions of treatment | Efficiency | Insurance coverage and cost comparison | Side effects | Drug Interactions | Warnings | Frequently Asked Questions
Percocet and Norco are two prescription pain relievers used to treat severe pain. They are classified into a group of medicines called opioid (narcotic) analgesics. They work by binding to mu receptors in the brain, dampening and blocking pain signals.
Thus, they relieve pain. Both drugs are classified by the DEA as Schedule II drugs. This means that they have a high potential for drug abuse and can lead to psychological or physical dependence. Percocet and Norco are known as opioid analgesics and have many similarities but also some notable differences.
What are the main differences between Percocet and Norco?
Percocet and Norco are combination medicines used to treat severe acute pain. Percocet (Percocet coupons | What is Percocet?) Contains oxycodone and acetaminophen. Acetaminophen is generic Tylenol, also known as APAP, so the name of the drug on your label might show up as oxycodone/APAP.
Norco contains hydrocodone and APAP. Both drugs are available in both brand-name and generic forms. Both drugs are intended for short-term pain relief, however, some patients continue to take Percocet or Norco for longer, depending on the doctor’s instructions.
All patients taking Percocet or Norco should be closely monitored.
| Main differences between Percocet and Norco | ||
|---|---|---|
| Percocet | Norco | |
| Drug class | Opioid (narcotic) analgesic | Opioid (narcotic) analgesic |
| Brand / generic status | Brand and generic | Brand and generic |
| What is the common name? | Oxycodone / APAP | Hydrocodone / APAP |
| What form(s) is the drug in? | Tablet | Tablet |
| What is the standard dosage? | Example: Oxycodone 5 mg / APAP 325 mg: 1 tablet every 4-6 hours as needed for pain. | Example: hydrocodone 5 mg / APAP 325 mg: 1 tablet every 4-6 hours as needed for pain. |
| How long does a typical treatment take? | For a short time, some patients continue treatment under the direction of a physician. | For a short time, some patients continue treatment under the guidance of a physician. |
| Who usually takes this medicine? | Adults | Adults |
Conditions treated by Percocet vs. Norco
Percocet and Norco are indicated for the relief of pain severe enough to require an opioid pain reliever. Percocet or Norco should only be used when other, non-opioid drugs are not tolerated or do not relieve pain properly.
| Condition | Percocet | Norco |
| Management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate | yes | yes |
Percocet or Norco more effective?
In a study of acute fracture emergency department patients treated with Percocet or Norco, pain relief was similar at 30 and 60 minutes with either drug.
The authors concluded that both drugs have similar analgesic effects. Another study came to the same conclusions; Pain relief was the same as Percocet or Norco – both drugs reduced pain by about 50%. One very small study of 20 patients concluded that Percocet was 1.5 times stronger than Norco.
The most effective pain medication should only be determined by your healthcare provider, who can get a complete picture of your condition(s) and medical history, as well as other medications you are taking.
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Percocet and Norco coverage and cost comparison
Percocet and Norco are covered by most insurance plans and Medicare Part D plans on a generic basis. For brands, you may pay a higher copay or the drug may not be covered. A typical prescription for generic Percocet is 20 5/325mg tablets and costs about $25-$50 out of pocket.
A typical Norco generic prescription is 20 5/325mg tablets, which can cost upwards of $100 out of pocket. You can get generic Percocet for about $14 and generic Norco for $27 to $42 with a SingleCare coupon.
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| Percocet | Norco 900 33 | |
| Usually covered by insurance? | yes | yes |
| Usually covered by Medicare Part D | yes | yes |
| Standard dosage | #20 hydrocodone/APAP tablets 5/325mg | |
| Typical Medicare copay | $0-25 | $0-100 |
| $14 | $10-16 |
Common side effects of Percocet and Norco
Serious side effects that may occur with Percocet or Norco include respiratory depression (slow breathing/lack of oxygen), apnea, respiratory arrest, hypotension (low blood pressure) and shock .
The most common side effects of Percocet are lightheadedness, dizziness, drowsiness/sedation, nausea and vomiting; followed by euphoria, dysphoria, constipation and itching (pruritus).
The most common side effects of Norco are dizziness, sedation, nausea and vomiting.
Serotonin syndrome is a serious life-threatening reaction that can occur when taking Percocet or Norco, especially when taken with other drugs that increase serotonin levels.
Other side effects may occur. Check with your healthcare provider for a complete list of side effects.
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Drug Interactions Percocet vs. Norco
Taking Percocet or Norco with certain drugs that are metabolized by CYP3A4 or CYP2D6 may result in drug interactions. These drugs are also known as enzyme inhibitors and include drugs such as macrolide antibiotics, azole antifungals, and protease inhibitors.
Using them with Percocet or Norco can cause opioids to build up in your body, which can be very dangerous.
Other drugs, known as enzyme inducers, have the opposite effect of inhibitors, lowering opioid levels so that they are ineffective or may even cause withdrawal symptoms.
The use of benzodiazepines or other CNS depressants (including other opioids) in combination with Percocet or Norco may result in hypotension (low blood pressure), respiratory depression, severe sedation, coma, or even death.
Taking Percocet or Norco with drugs that increase serotonin levels increases the risk of serotonin syndrome, which can be very serious or even life-threatening. These drugs include certain antidepressants such as SSRIs, SNRIs and tricyclic antidepressants, muscle relaxants, MAOIs (MAOIs should not be used within 14 days of taking Percocet or Norco), and triptans for migraine.
If you are taking Percocet or Norco, remember that the medicine contains APAP, and many over-the-counter cough or cold medicines and pain relievers also contain APAP.
Talk to your pharmacist, who can help you choose an over-the-counter drug that does not contain APAP.
Consult your healthcare professional for a complete list of drug interactions.
| Drug | Drug class | Percocet | Norco |
| Erythromycin Biaxin (clarithromycin) | Macrolide antibiotics | yes | yes |
| Diflucan (fluconazole) Nizoral (ketoconazole) | Azole antifungal | yes | yes |
| Norvir (ritonavir) | Protease inhibitors | yes | yes |
| Rifampicin Tegretol (carbamazepine) Dilantin (phenytoin) | CYP3A4 inducers | yes | yes |
| Benzodiazepines | yes | yes | |
| Methadone Ultram (Tramadol) Tylenol with Codeine (APAP / Codeine) Duragesic (Fentanyl) Morphine 900 34 | Opioids | yes | yes |
| Alcohol | Alcohol | yes | yes |
| Muscle relaxants | yes | yes | |
| Imitrex (sumatriptan) Maxalt (rizatriptan) | Triptans | yes | yes |
| Prozac (fluoxetine) Paxil (paroxetine) Zoloft (sertraline) Celexa (citalopram) Lexapro (escitalopram) | SSRI antidepressants | yes | yes | Pamelor (nortriptyline) Elavil (amitriptyline) | Tricyclic antidepressants | yes | yes |
| Cymbalta (duloxetine) Effexor (venlafaxine) Pristiq (desvenlafaxine) | SNRI antidepressants | yes | yes |
| Hydrochlorothiazide Lasix (furosemide) | Diuretics | yes | yes |
| MAO inhibitors | yes | yes | |
| Inderal (propranolol) Lopressor, Toprol XL (metoprolol) | Beta blockers | yes | yes |
| Cogentin (benztropine) Benadryl (diphenhydramine) Ditropan (oxybutynin) Detrol (tolterodine) | Anticholinergics | yes | yes |
Here are additional warnings:
If the combination cannot be avoided, the lowest dose should be used for the shortest duration and the patient should be closely monitored.
It contains hydrocodone and acetaminophen.
Sometimes they can be used together on a short-term basis, depending on the occasion. Check with your doctor before using any other prescription or over-the-counter medicines in combination with Percocet or Norco.
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