What is the mechanism of action of hydrocodone and acetaminophen? What are the approved uses for this combination therapy? What are the adverse events and contraindications to be aware of? How can the interprofessional team improve care coordination and communication to optimize outcomes and minimize misuse?

Hydrocodone and Acetaminophen: Understanding the Mechanism of Action

Hydrocodone is a potent opioid agonist that primarily acts on the mu-opioid receptors in the body, leading to inhibition of pain reflexes and profound analgesia. It also interacts, to a lesser extent, with delta receptors. Activated opioid receptors inhibit the release of neurotransmitters, including substance P, which plays a crucial role in pain signaling. Hydrocodone reaches peak serum concentrations within an hour and has an elimination half-life of 4 to 6 hours. It requires metabolism by the CYP2D6 enzyme to its active form, hydromorphone.

Acetaminophen’s mechanism of analgesia is not fully understood, but it is believed to involve inhibition of cyclooxygenase (COX) enzymes and activation of descending serotonergic inhibitory pathways in the central nervous system. Acetaminophen also has antipyretic effects through the inhibition of the hypothalamic heat-regulating center. The drug is readily absorbed from the gastrointestinal tract, with a plasma half-life ranging from 1 to 3 hours, though it may increase due to liver damage following overdose.

Approved Uses for Hydrocodone and Acetaminophen Combination Therapy

Hydrocodone is one of the most commonly prescribed pain medications and is widely used for moderate-to-severe pain control in postoperative patients, individuals with trauma, and patients with cancer. The combination of hydrocodone and acetaminophen has been shown to be more effective than placebo in multiple randomized studies, without significant changes in adverse effects. Additionally, this combination is commonly used as an antitussive agent to suppress cough.

Dosing Regimen for Pain Management

The lowest effective dose of hydrocodone and acetaminophen should be used, and the dosage should be titrated individually for each patient. For initial oral tablet therapy, the usual adult dose is one or two tablets (5 mg hydrocodone / 300 mg acetaminophen) every four to six hours as needed, with a maximum daily dosage of eight tablets. For initial oral solution therapy, the usual adult dose is one tablespoon (15 mL of 7.5 mg hydrocodone / 325 mg acetaminophen) every four to six hours, with a maximum daily dosage of six tablespoons.

Adverse Events and Contraindications

Hydrocodone and acetaminophen combination therapy can have significant adverse effects, including respiratory depression, constipation, nausea, vomiting, and sedation. Acetaminophen overdose can lead to hepatotoxicity, which can be life-threatening. Contraindications include hypersensitivity to either component, acute or severe bronchial asthma, and paralytic ileus. Caution is advised in patients with liver disease, renal impairment, or concurrent use of other medications that may interact with hydrocodone or acetaminophen.

Interprofessional Strategies for Optimal Outcomes

Given the ongoing opioid crisis, it is crucial for the interprofessional team to work together to improve care coordination and communication in the use of hydrocodone and acetaminophen. This includes careful patient selection, close monitoring for signs of misuse or abuse, and comprehensive patient education on the appropriate use, potential risks, and safe storage and disposal of these medications. Regular communication among prescribers, pharmacists, and other healthcare providers can help to identify and address any issues or concerns promptly, ultimately improving patient outcomes and minimizing the risk of adverse events or misuse.

Conclusion

In summary, the combination of hydrocodone and acetaminophen is a widely used and effective treatment for moderate-to-severe pain, as well as an antitussive agent. Understanding the mechanism of action, approved uses, dosing regimen, adverse events, and contraindications is crucial for healthcare providers to ensure optimal patient outcomes. By implementing interprofessional strategies for care coordination and communication, the healthcare team can help to mitigate the risks associated with these medications, especially in light of the ongoing opioid crisis.

Key Takeaways

• Hydrocodone is a potent opioid agonist that primarily acts on mu-opioid receptors, while acetaminophen’s mechanism of analgesia is not fully understood but likely involves COX inhibition and activation of descending serotonergic pathways.
• The combination of hydrocodone and acetaminophen is approved for the management of moderate-to-severe pain and as an antitussive agent.
• Dosing should be individualized, with the lowest effective dose used, and close monitoring for adverse events such as respiratory depression, constipation, and hepatotoxicity.
• Interprofessional collaboration and communication are essential to ensure optimal patient outcomes and minimize the risk of misuse or abuse, especially in the context of the ongoing opioid crisis.

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. 

 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.

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]

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. 

 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.

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]

Disclosure: Manuchehr Habibi declares no relevant financial relationships with ineligible companies.

Disclosure: Peggy Kim declares no relevant financial relationships with ineligible companies.

Hydrocodone – instructions for use

Hydrocodone

Instruction:

• Pharmacological action
• Readings
• Pregnancy and breastfeeding
• Dosage and Administration
• Side effects
• Overdose
• Interaction
• Special instructions
• Precautions
• Classification

Pharmacological action

Hydrocodone is a semi-synthetic opioid derived from the natural opiates codeine or thebaine, belongs to the morphine group. Hydrocodone is an orally effective narcotic analgesic and cough suppressant. In medical practice, it is used as an antitussive agent in the form of hydrocodone phosphate. Hydrocodone reduces pain by binding to opioid receptors in the brain and spinal cord. It is commonly available in tablets, capsules, syrup form, and is found in many medications. It acts as an analgesic and a powerful cough suppressant.

Indications

Pain, severe cough.

Pregnancy and breastfeeding

Use in pregnancy

FDA fetal category C.

There are no adequate and well-controlled studies on the safety of hydrocodone during pregnancy.

Animal studies have shown no fetal malformations at doses 2 to 10 times the maximum recommended in humans.

Prescribing opioids can lead to physical dependence in newborns.

Hydrocodone may harm the fetus during pregnancy. The use of the drug during pregnancy is prohibited, it can lead to breathing problems and even miscarriage. Application is contraindicated.

Use during breastfeeding

During breastfeeding, the use of hydrocodone can cause drowsiness, central nervous system depression and even death in the baby. Newborns are especially sensitive.

Contraindicated during breastfeeding.

Dosage and administration

Inside.

Children, pain: 150 mcg/kg every 6 hours.

Adults, pain: 5–10 mg every 4–6 hours; cough: 5 mg every 4 to 6 hours.

Side effects

• Headache;
• swelling of the face, hands, feet;
• body aches;
• chills, fever;
• cough, sore throat;
• depression;
• sensation of fear;
• nervousness;
• labored breathing;
• nasal congestion;
• fatigue;
• unusual increase or decrease in body weight;
• allergic reactions.

Overdose

Symptoms of hydrocodone overdose

Difficulty breathing, extreme drowsiness, numbness, cold and/or clammy skin, bradycardia, hypotension, coma.

Consequences of hydrocodone overdose

Severe overdose can lead to cardiac arrest, death.

Mixing hydrocodone with alcohol, narcotics, amphetamines, barbiturates can cause serious adverse effects including cardiac arrest, heart attack, respiratory arrest, liver and/or kidney failure, jaundice, amnesia, blindness and coma.

Interactions

Drinking with alcohol may increase drowsiness.

Interaction with monoamine oxidase inhibitors, as well as other drugs, may cause drowsiness.

Precautions

Hydrocodone intake should not exceed 40 mg in patients with opiate sensitivity. The typical therapeutic range is 5-60 mg per day, in 4-6 doses of 2.5-10 mg. When prescribing combined agents with paracetamol (acetaminophen/APAP in some countries), do not exceed 4,000 mg of paracetamol per day.

For chronic pain patients increase the dose to 180 mg of hydrocodone per day (only in opioid dependent, increase slowly! fatal for a new patient).

Precautions

Included in the list of narcotic drugs, the circulation of which is prohibited in Russia.

Classification

• ATX

  R05DA03

• Pharmacological group

  Opioid narcotic analgesics

• ICD codes 10

  R07.0 Sore throat

  R05 Cough

• FDA pregnancy category

  C
  (risk not excluded)

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Learn more about the active substance Hydrocodone:

• Reviews
• Questions
• Latin name
• Chemical formula

Information about the active substance Hydrocodone is intended for medical and pharmaceutical professionals, for reference purposes only. The instructions are not intended to replace professional medical advice, diagnosis or treatment. The information contained here may change over time. The most accurate information on the use of preparations containing the active substance Hydrocodone is contained in the manufacturer’s instructions attached to the package.

Acetaminophen Hydrocodone Side Effects, Dosage, Uses and More

Contents

Acetaminophen Hydrocodone Isolate

FDA Warnings

• This drug has black box warnings. The black box warning is the most severe warning from the Food and Drug Administration (FDA). A black box warning alerts doctors and patients to exposure to drugs that may be dangerous.
• It can be addictive, abusive and abusive. Taking this drug increases the risk of addiction, misuse, and abuse of opioids. This can lead to overdose and death. Talk to your doctor if you are concerned about the properties of this addictive drug.
• May slow or stop breathing. Hydrocodone in high doses can affect the parts of your brain that control your breathing. If you have trouble breathing, contact your doctor immediately or seek emergency medical attention.
• Accidental ingestion by children. Swallowing even one dose of this drug can be fatal for a child. Keep away from children.
• May cause neonatal withdrawal syndrome. If you use this medicine during pregnancy, your baby may have problems living after birth. This is called neonatal opioid withdrawal syndrome. Problems with the newborn are more likely if you take this medicine for a long time during pregnancy. Talk to your doctor if you are pregnant or planning to become pregnant.
• Drug interactions. Hydrocodone and acetaminophen destroy your liver. If you take these medicines with another drug that can affect your liver, hydrocodone and acetaminophen can build up in your body and cause more breathing problems and other side effects. Your doctor may need to change or stop taking this medicine or other medicines.
• May cause liver failure. Taking too much acetaminophen can cause liver failure. Sometimes this results in the need for a liver transplant or death. Most reported cases of liver damage have occurred when a person has taken more than 4,000 mg of acetaminophen per day, usually along with more than one acetaminophen-containing product. The risk of liver failure is higher in people who already have liver disease and in people who drink alcohol while taking acetaminophen.
• Use in depression of the central nervous system (CNS). Taking opioids with CNS depressants such as benzodiazepines or alcohol can lead to excessive sedation, slowed breathing, coma, and death.

Other warnings

• Severe allergic reaction warning: This medicine may cause a serious, potentially life-threatening allergic reaction. The reaction can happen very quickly. Symptoms may include:
  • breathing problems
  • swelling of the face, throat and mouth
  • tingling
  • itching
  • vomiting

noah medical assistance.

• Adrenal warning: This medicine may cause your adrenal glands to stop working as well. Symptoms may include:
  • nausea
  • vomiting
  • loss of appetite
  • humor
  • weakness
  • dizziness
  • dizziness

If you have these symptoms, talk to your doctor. You may need to stop taking this medicine or have some tests.

Acetaminophen-hydrocodone is available by prescription. As an opioid, it is a controlled substance. It comes as an oral tablet and an oral solution.

Acetaminophen-hydrocodone oral tablets are available as Norco and Vicodin protected formulations. It is also available in generic form. Generic drugs usually cost less than brand names. In some cases, they may not be available in all strengths or forms as a branded version.

This drug is a combination of two or more drugs in one form. It is important to know about all the medicines in the combination because each medicine can affect you differently.

Why it is used

Acetaminophen-hydrocodone oral tablet is used to treat moderate to severe pain that other treatments have failed to relieve.

How it works

This drug is a combination of hydrocodone and acetaminophen. Hydrocodone is an opioid (drug) and acetaminophen is an analgesic (pain reliever). Both drugs are used to reduce pain.

These drugs work in your brain to block pain signals. They reduce your ability to feel pain.

Acetaminophen-Hydrocodone Oral Tablet may make you drowsy, dizzy, or faint. Avoid driving or using machinery until you know how your body reacts to this medicine.

This medicine may cause other side effects.

More common side effects

Common side effects that may occur with hydrocodone acetaminophen include:

• drowsiness or drowsiness
• dizziness or weakness
• nausea
• vomiting
• closure

Serious side effects

9000 2 Call your doctor if you have serious side effects. Call 911 if your symptoms seem life-threatening or if you think you need emergency medical attention. Serious side effects and their symptoms may include the following:

• Skin rash
• Swelling of the face, throat and mouth
• Liver problems, including liver failure. Symptoms may include:
  • yellowing of the skin and whiteness of the eyes
  • pain in the upper right abdomen
  • swelling of the abdomen
  • itching
  • confusion
  • fatigue
  • lack of appetite 90 006
  • Breathing problems
  • Drug addiction

Disclaimer: Our goal is to provide you with the most current and up-to-date information. But because drugs affect each person differently, we cannot guarantee that this information includes all possible side effects. This information does not replace medical advice. Always discuss possible side effects with a doctor who knows your medical history.

Acetaminophen-hydrocodone oral tablet may interact with other medicines, vitamins, or herbs you are taking. An interaction is when a substance changes the way a drug works. It can be harmful or prevent the medicine from working well.

To avoid interactions, your doctor must carefully administer all of your medicines. Tell your doctor about any medications, vitamins, or herbs you are taking. To find out how this medicine may interact with other medicines you are taking, talk to your doctor or pharmacist.

Examples of drugs that may cause interactions with acetaminophen-hydrocodone are listed below.

Drugs that cause drowsiness

Taking certain drugs with acetaminophen-hydrocodone increases the risk of drowsiness, dizziness, fatigue, and decreased physical and mental function. If you need to use one of these medicines with acetaminophen hydrocodone, the dosage of one or both medicines should be reduced.

Examples of such preparations include:

• other opioids (narcotics)
• antihistamines used for allergies
• neuroleptics used for bipolar disorder, schizophrenia or depression
• benzodiazepines used for anxiety

90 038 Drugs that increase serotonin

Taking this medicine with medicines which increase the amount of a chemical called serotonin in your body can cause a serious problem. This problem, called serotonin syndrome, can be fatal. Tell your doctor if you are taking any of these medicines:

• certain antidepressants (selective serotonin reuptake inhibitors [SSRIs], selective serotonin and norepinephrine reuptake inhibitors [SNRIs], tricyclic antidepressants [TCAs], monoamine oxidase inhibitors [MAOIs], mirtazapine, trazodone)
• certain migraine medicines (triptans)
• certain medicines for nausea, such as ondansetron
• tramadol, used for pain
• linezolid, which is an antibiotic

Medicines that inhibit the activity of certain liver enzymes

Taking this medicine with medicines that can inhibit the activity of certain liver enzymes may increase the amount of hydrocodone in the body and cause more side effects. You may experience increased breathing problems or drowsiness. Examples of such drugs include:

• erythromycin
• ketoconazole
• protease inhibitors used to treat HIV, such as ritonavir

Medicines that increase the activity of certain liver enzymes

Taking this drug with medicines that can increase the activity of certain liver enzymes may reduce the amount of hydrocodone or acetaminophen in the body. You may need a higher dose of this pain medication. Examples of such drugs include:

• rifampicin
• carbamazepine
• phenytoin

Disclaimer: Our goal is to provide you with the most current and up-to-date information. However, because drugs affect each person differently, we cannot guarantee that these data include all possible interactions. This information does not replace medical advice. Always talk to your doctor about potential interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter medications you are taking.

This medicine comes with several caveats.

Allergy Warning

This medicine may cause a severe allergic reaction. Symptoms may include:

• trouble breathing
• swelling of the throat or tongue
• Osip
• Osip
• itching

If you have these symptoms, call 911 or go to the nearest emergency room.

Do not take this medicine again if you have ever had an allergic reaction to it. Repeated use may be lethal (lead to death).

Alcohol Interaction Warning

You must not drink alcohol while taking acetaminophen-hydrocodone. Drinking alcohol while taking this medicine may cause:

• slow or stopped breathing
• Hangover
• humor
• mental cloudiness
• physical and mental retardation

Combined drinking alcohol with this drug also increases the risk of liver problems and damage.

Warnings for people with certain medical conditions

For people with a head injury: If you have a head injury, hydrocodone can cause high blood pressure in your brain and cause breathing problems.

For people with stomach problems: Be careful when taking this medicine if you have intestinal blockage, ulcerative colitis, or constipation. This medicine may make your symptoms worse.

For people with severe kidney disease: This medicine may accumulate in the body, which can cause difficulty breathing and other side effects.

For people with lung disease: If you have lung disease, you may have trouble breathing while taking this medicine.

For people with severe liver disease: If you have severe liver disease, your risk of liver failure is increased. Also, this medicine can build up in the body, which can cause breathing problems and other side effects.

For people with an enlarged prostate: If you have an enlarged prostate, taking hydrocodone acetaminophen may cause more difficulty urinating.

For people with asthma: If you have severe or uncontrolled asthma, do not use this medicine without talking to your doctor. You may need to take your first few doses in a controlled environment.

For pregnant women: This is a category C pregnancy drug. This means two things:

Tell your doctor if you are pregnant or plan to become pregnant. Children born to mothers who regularly take opioids such as hydrocodone may be born physically dependent on the drug. This can cause withdrawal symptoms or neonatal opioid withdrawal syndrome. Symptoms may include:

• excessive crying
• sneezing
• wave
• rapid breathing
• increased defecation
• yawning
• vomiting
• high fever

There is also a higher chance that the baby will have difficulty breathing if the mother is given this medicine just before birth.

For lactating women: Acetaminophen is excreted in breast milk in small amounts. Hydrocodone also passes into breast milk and can cause excessive fatigue and slow breathing in a breastfed baby.

Breastfeeding while taking this medicine may be risky. You and your doctor must decide whether to take this medicine or breastfeed.

For the elderly: Older people may have decreased kidney, liver and heart function. If you are older, your doctor may start with a small dose of this medication.

This does not include all possible dosages and forms of medicines. Your dose, form of medication, and how often you take the medication will depend on:

• your age
• the condition being treated
• the severity of your condition
• other health conditions you have
• how you respond to the first dose

Forms and strengths

Generic: acetaminophen-hydrocodone

• Form: oral tablet
• benefits:
  • hydrocodone 5 mg / acetaminophen 300 mg

  900 05 hydrocodone 7.5 mg / acetaminophen 300 mg

  • hydrocodone 10 mg / acetaminophen 300 mg
  • hydrocodone 2.5 mg / acetaminophen 325 mg
  • hydrocodone 5 mg / acetaminophen 325 mg
  • hydrocodone 7. 5 mg / acetaminophen 325 mg
  • hydrocodone 10 mg / acetaminophen 325 mg

Brand: Norco

• Form: oral tablet
• Benefits:
  • 2.5 mg hydrocodone / 325 mg acetaminophen
  • 5 mg hydrocodone / 325 mg acetaminophen
  • 7.5 mg hydrocodone / 325 mg acetaminophen
  • 10 mg hydrocodone / 325 mg acetaminophen

Brand name: Vicodin

• Form: oral tablet
• Strength: 5 mg hydrocodone / 300 mg acetaminophen.

Trade name: Vicodin EU

• Form: oral tablet
• Strength: 7.5 mg hydrocodone / 300 mg acetaminophen.

Brand: Vicodin HP

• Form: oral tablet
• Strength: 10 mg hydrocodone / 300 mg acetaminophen.

Dosage for moderate to severe pain

Dosage for adults (over 18 years and over 101 kg [46 kg])

• 5 mg or 2.5 mg hydrocodone / 300 mg or 325 mg acetaminophen: The usual dose is 1 -2 tablets every 4 to 6 hours, as needed. The maximum dose is 8 tablets per day.
• 7.5 mg or 10 mg hydrocodone / 300 mg or 325 mg acetaminophen: The usual dose is 1 tablet taken over 4-6 hours as needed. The maximum dose is 6 tablets per day.

Pediatric dose (age 0-17 years)

• Dosage for persons under 18 years of age has not been established.

Disclaimer: Our goal is to provide you with the most current and up-to-date information. But because drugs affect each person differently, we cannot guarantee that this list includes all possible doses. This information does not replace medical advice. Always talk to your doctor or pharmacist about the doses that are right for you.

Hydrocodone acetaminophen is used for short or long term treatment. There is a risk if you do not take it exactly as prescribed by your doctor.

If you stop taking your medicine or don’t take it at all: your pain will continue and get worse.

If you miss a dose or don’t take your medicine as scheduled: The medicines may not work properly or may stop working completely. For this medicine to work well, a certain amount must be in your system at all times.

What to do if you miss a dose: If you take your medicine regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose.

Do not use additional medicines to make up for a missed dose. This can lead to dangerous side effects.

If you take too much: If you take too much, you may overdose on this medicine. You can experience: 9Slow or stopped breathing possible coma

If you think you have taken too much of this medication, call your doctor or seek help from the American Association of Poison Control Centers at 1-800-222-1222 or the online tool But if you have severe symptoms, call 911 or immediately go to the nearest emergency room.

How to tell if a medicine is working: Your pain should decrease.

Important considerations for taking this medicine

Keep this in mind if your doctor prescribes hydrocodone acetaminophen.

Basic information

• Take with food to reduce the risk of stomach upset.
• You can cut or crush an oral tablet.

Warehouse

• Store this medicine between 68°F and 77°F (20°C to 25°C).
• Keep it in a child’s closure container.
• Keep this medicine away from light.

tapping

There is no prescription for this drug. You or your pharmacy will need to talk to your doctor about a new prescription if you need a different medicine.

Travel

When traveling with medication:

• Always carry your medication with you. Never put it in your checked bag while flying. Keep it in your bag.
• Don’t worry about air devices at the airport. I can’t hurt drugs.
• You may need to show the pharmacy sticker for your medicines to the airport staff. Always carry the original prescription container with you.
• Do not put this medicine in the glove compartment of your car or leave it in your car. Be sure to avoid this when the weather is very hot or very cold.

Clinical monitoring

Your doctor may do certain tests to see if you have severe liver or kidney disease. These tests will check your:

• Kidney function. Your doctor may do kidney tests if you have kidney problems to make sure this medication is safe for you and won’t cause breathing problems.
• Liver function. Your doctor may do liver tests if you have liver problems to make sure this medicine is safe for you and won’t cause breathing problems.

Pre-Approval

Most insurance companies do not require pre-approval for this drug.

There are other medicines available to treat your condition. Some of them may be more convenient for you than others. Talk to your doctor about other treatment options that may be right for you.

Disclaimer: Healthline has made every effort to ensure that all information is correct, complete, and up-to-date. However, this article should not be used as a substitute for the knowledge and experience of a licensed healthcare professional.