LORTAB 7.5/325mg. Tablets.

BOXED WARNING

Acetaminophen; hydrocodone is contraindicated for use in patients with significant respiratory depression and in patients with acute or severe asthma (e.g., status asthmaticus) in unmonitored care settings or in the absence of resuscitative equipment. Receipt of moderate hydrocodone doses in these patients may significantly decrease pulmonary ventilation. Additionally, avoid coadministration with other CNS depressants when possible, as this significantly increases the risk for profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; if concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Monitor patients closely for signs or symptoms of respiratory depression or sedation. In patients with chronic obstructive pulmonary disease (COPD), cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, respiratory insufficiency, upper airway obstruction, or preexisting respiratory depression, it is recommended that non-opioid analgesics be considered as alternatives to hydrocodone, as even usual therapeutic doses of hydrocodone may decrease respiratory drive and cause apnea in these patient populations. Extreme caution should also be used in patients with chronic asthma, kyphoscoliosis (a type of scoliosis), hypoxemia, or paralysis of the phrenic nerve. Patients with advanced age, debilitation, or sleep apnea are at an increased risk for the development of respiratory depression associated with hydrocodone. Use with caution in patients with obesity as this is a risk factor for obstructive sleep-apnea syndrome and/or decreased respiratory reserve. Hydrocodone should not be used during impaired consciousness or coma, as significant decreases in respiratory drive may lead to adverse intracranial effects from carbon dioxide retention. Respiratory depression, if left untreated, may cause respiratory arrest and death. Symptoms of respiratory depression include a reduced urge to breathe, a decreased respiratory rate, or deep breaths separated by long pauses (a “sighing” breathing pattern). Carbon dioxide retention from respiratory depression may also worsen opioid sedating effects. Careful monitoring and dose titration is required, particularly when CYP450 3A4 inhibitors or inducers are used concomitantly; concurrent use of a CYP3A4 inhibitor or discontinuation of a concurrently used CYP3A4 inducer may increase plasma hydrocodone concentrations and potentiate the risk of fatal respiratory depression. Management of respiratory depression should include observation, necessary supportive measures, and opioid antagonist use when indicated.

Acetaminophen has been associated with acute liver failure, with some cases resulting in liver transplant and death. Most cases of liver injury are associated with the use of acetaminophen at doses exceeding 4 g per day and often involve the use of more than 1 acetaminophen-containing product. Advise patients receiving acetaminophen to carefully read OTC and prescription labels, to avoid excessive and/or duplicate medications, and to seek medical help immediately if more than 4 g of acetaminophen is ingested in 1 day, even if they feel well. It is important to note that the risk of acetaminophen-induced hepatotoxicity is increased in patients with pre-existing hepatic disease (e.g., hepatitis), those who ingest alcohol (e.g., ethanol intoxication, alcoholism), those with chronic malnutrition, and those with severe dehydration. In patients with chronic hepatic disease, acetaminophen can be used safely in recommended doses and is often preferred to nonsteroidal anti-inflammatory drugs (NSAIDs) due to the absence of platelet impairment, gastrointestinal toxicity, and nephrotoxicity. Though the half-life of acetaminophen may be prolonged, repeated dosing does not result in drug or metabolite accumulation. In addition, cytochrome P450 activity is not increased and glutathione stores are not depleted in hepatically impaired patients taking therapeutic doses, therefore toxic metabolite formation and accumulation is not altered. Although it is always prudent to use the smallest dose of acetaminophen for the shortest duration necessary, courses less than 2 weeks in length have been administered safely to adult patients with stable chronic liver disease. If use acetaminophen in patients with severe hepatic disease, monitor serial liver function tests. Additionally, patients with hepatic impairment may have higher plasma hydrocodone concentrations compared to those with normal hepatic function. Use a low initial dose of acetaminophen; hydrocodone in patients with hepatic impairment, and monitor for sedation and respiratory depression. Consumption of ethanol will result in additive CNS depressant effects. Advise patients to avoid ethanol ingestion and ethanol intoxication, including the ingestion of alcohol contained in prescription or non-prescription medications, during therapy. Patients with alcoholism should be advised of this serious risk, or an alternative medication should be used.

Hydrocodone is an opioid agonist and therefore has abuse potential and risk of fatal overdose from depressed respiration. Addiction may occur in patients who obtain hydrocodone illicitly or in those appropriately prescribed the drug. The risk of addiction in any individual is unknown. However, patients with mental illness (e.g., major depression) or a family history of substance abuse (including alcoholism) have an increased risk of opioid abuse. Assess patients for risks of addiction, abuse, or misuse before drug initiation, and monitor patients who receive opioids routinely for development of these behaviors or conditions. A potential risk of abuse should not preclude appropriate pain management in any patient, but requires more intensive counseling and monitoring. Abuse and addiction are separate and distinct from physical dependence and tolerance; patients with addiction may not exhibit tolerance and symptoms of physical dependence. To discourage abuse, the smallest appropriate quantity of hydrocodone should be dispensed, and proper disposal instructions for unused drug should be given to patients.

Like all opioid analgesics, hydrocodone is associated with a significant potential for overdose or poisoning; proper patient selection and counseling is recommended. Hydrocodone should be kept out of the reach of pediatric patients, others for whom the drug was not prescribed, and pets as accidental exposure may cause respiratory failure and a fatal overdose.

There are no adequate and well-controlled studies of acetaminophen; hydrocodone in pregnant women. Hydrocodone readily crosses the placenta. Use acetaminophen; hydrocodone during pregnancy only if the potential benefit clearly justifies the potential risk to the fetus. Hydrocodone is not recommended for use in women during and immediately prior to labor and obstetric delivery because oral opioid agonists may cause respiratory depression in the newborn. Opioid analgesics can prolong labor by reducing the strength and frequency of uterine contractions; however, this effect may be offset by an increased rate of cervical dilation. Further, prolonged maternal use of acetaminophen; hydrocodone during pregnancy may result in neonatal opioid withdrawal syndrome (NOWS). This syndrome can be life-threatening. Severe symptoms may require pharmacologic therapy managed by clinicians familiar with neonatal opioid withdrawal. Monitor the neonate for withdrawal symptoms including irritability, hyperactivity, abnormal sleep pattern, high-pitched crying, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity of opioid withdrawal may vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination by the newborn. No overall increase in fetal mortality, as determined by pregnancy outcomes of mothers that overdosed on various amounts of acetaminophen, was apparent in an analysis of 300 women. Treatment with acetylcysteine or methionine did not appear to affect fetal or neonatal toxicity. Of 235 babies exposed to an overdose of only acetaminophen, 168 were normal, 8 had malformations, 16 were spontaneously aborted, and 43 were electively terminated. Of 67 babies exposed to an overdose of a combination acetaminophen product, 51 were normal, 3 had malformations, 2 were spontaneously aborted (late fetal deaths), and 11 were electively terminated. None of the babies with malformations were exposed during the first trimester, but all of the spontaneous abortions and 1 of the late fetal deaths were subsequent to first trimester exposure.

DEA CLASS

Rx, schedule II

DESCRIPTION

Combination product to treat moderate to severe pain. Acetaminophen is a non-salicylate analgesic; hydrocodone is a semisynthetic opiate agonist. The combination produces additive analgesia as compared to either agent alone.

COMMON BRAND NAMES

Anexsia, Hycet, Lorcet, Lorcet HD, Lorcet Plus, Lortab, Norco, Verdrocet, Vicodin, Vicodin ES, Vicodin HP, Xodol, Zamicet

HOW SUPPLIED

Anexsia/Hydrocodone Bitartrate, Acetaminophen/Lorcet/Lorcet HD/Lorcet Plus/Lortab/Norco/Verdrocet/Vicodin/Vicodin ES/Vicodin HP/Xodol Oral Tab: 10-300mg, 10-325mg, 2.5-325mg, 5-300mg, 5-325mg, 7.5-300mg, 7.5-325mg
Hycet/Hydrocodone Bitartrate, Acetaminophen/Lortab/Zamicet Oral Sol: 7.5mL, 15mL, 10-300mg, 10-325mg, 5-163mg, 7.5-325mg
Hydrocodone Bitartrate, Acetaminophen Oral Elixir: 5mL, 2.5-167mg

DOSAGE & INDICATIONS

MAXIMUM DOSAGE

The maximum dosage is dependent on the product. Do not exceed a total daily dose of 4 grams of acetaminophen from ALL sources.

The maximum dosage is dependent on the product. Do not exceed a total daily dose of 4 grams of acetaminophen from ALL sources.

>= 46 kg (101 pounds): acetaminophen 3 g/day PO; the maximum dose of the hydrocodone in the combination product is limited by the total daily limit of acetaminophen.
32—45 kg (70—100 pounds): acetaminophen 2 g/day PO; the maximum dose of the hydrocodone in the combination product is limited by the total daily limit of acetaminophen.

>= 2 years and 23—31 kg (51—69 pounds): acetaminophen 1.5 g/day PO; the maximum dose of the hydrocodone in the combination product is limited by the total daily limit of acetaminophen.
>= 2 years and 16—22 kg (35—50 pounds): acetaminophen 1 g/day PO; the maximum dose of the hydrocodone in the combination product is limited by the total daily limit of acetaminophen.
>= 2 years and 12—15 kg (27—34 pounds): acetaminophen 750 mg/day PO; the maximum dose of the hydrocodone in the combination product is limited by the total daily limit of acetaminophen.
< 2 years or < 12 kg: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Dosage should be modified depending upon the clinical response and degree of hepatic impairment. No quantitative recommendations are available.

Dosage should be modified depending upon the clinical response and degree of renal impairment. No quantitative recommendations are available.

ADMINISTRATION

Administer with a full glass of water. May be taken food or milk to minimize GI irritation.
Acetaminophen; hydrocodone should be titrated to the dose required to relieve the patient’s pain keeping in mind the maximum daily dose of acetaminophen. Careful titration in opioid-naive patients is required until tolerance develops to some of the side effects (i.e., drowsiness, respiratory depression).

STORAGE

Generic:
– Avoid exposure to heat
– Do not refrigerate
– Store at controlled room temperature (between 68 and 77 degrees F)
Anexsia:
– Store at controlled room temperature (between 68 and 77 degrees F)
Bancap HC :
– Protect from light
– Protect from moisture
– Store at controlled room temperature (between 68 and 77 degrees F)
Ceta-Plus:
– Protect from light
– Protect from moisture
– Store at controlled room temperature (between 68 and 77 degrees F)
Co-Gesic:
– Protect from light
– Store at controlled room temperature (between 68 and 77 degrees F)
Comfortpak :
– Protect from light
– Store at controlled room temperature (between 68 and 77 degrees F)
Dolagesic:
– Protect from light
– Protect from moisture
– Store at controlled room temperature (between 68 and 77 degrees F)
Dolorex Forte:
– Protect from light
– Protect from moisture
– Store at controlled room temperature (between 68 and 77 degrees F)
DuoCet :
– Protect from light
– Store at controlled room temperature (between 68 and 77 degrees F)
Hycet:
– Store at controlled room temperature (between 68 and 77 degrees F)
Hydrocet :
– Protect from light
– Protect from moisture
– Store at controlled room temperature (between 68 and 77 degrees F)
Hydrogesic:
– Protect from light
– Protect from moisture
– Store at controlled room temperature (between 68 and 77 degrees F)
Liquicet:
– Store at controlled room temperature (between 68 and 77 degrees F)
Lorcet:
– Store at controlled room temperature (between 68 and 77 degrees F)
Lorcet HD:
– Store at controlled room temperature (between 68 and 77 degrees F)
Lorcet Plus:
– Store at controlled room temperature (between 68 and 77 degrees F)
Lortab:
– Store at controlled room temperature (between 68 and 77 degrees F)
Margesic H:
– Protect from light
– Protect from moisture
– Store at controlled room temperature (between 68 and 77 degrees F)
Maxidone:
– Store between 68 to 77 degrees F
Norco:
– Store at controlled room temperature (between 68 and 77 degrees F)
Polygesic:
– Protect from light
– Protect from moisture
– Store at controlled room temperature (between 68 and 77 degrees F)
Stagesic:
– Protect from light
– Protect from moisture
– Store at controlled room temperature (between 68 and 77 degrees F)
Vanacet:
– Protect from light
– Store at controlled room temperature (between 68 and 77 degrees F)
Verdrocet:
– Store at controlled room temperature (between 68 and 77 degrees F)
Vicodin:
– Store at controlled room temperature (between 68 and 77 degrees F)
Vicodin ES:
– Store at controlled room temperature (between 68 and 77 degrees F)
Vicodin HP:
– Store at controlled room temperature (between 68 and 77 degrees F)
Xodol:
– Store at controlled room temperature (between 68 and 77 degrees F)
Zamicet :
– Store at controlled room temperature (between 68 and 77 degrees F)
Zolvit :
– Do not refrigerate
– Protect from extreme heat
– Store at controlled room temperature (between 68 and 77 degrees F)
Zydone:
– Store at 77 degrees F; excursions permitted to 59-86 degrees F

CONTRAINDICATIONS / PRECAUTIONS

NOTE: This monograph discusses the contraindications/precautions of acetaminophen; hydrocodone combination products. Clinicians may wish to consult the individual monographs for more information about each agent.

Acetaminophen; hydrocodone is contraindicated in patients with acetaminophen hypersensitivity. Acetaminophen hypersensitivity reactions are rare, but severe sensitivity reactions are possible. Although true opiate agonist hypersensitivity is rare, the use of acetaminophen; hydrocodone is contraindicated in patients with hydrocodone hypersensitivity.

Hydrocodone is contraindicated in patients with known or suspected GI obstruction, including paralytic ileus. Due to the effects of opioid agonists on the gastrointestinal tract, hydrocodone should be used cautiously in patients with GI disease, such as ulcerative colitis (UC). Patients with UC or other inflammatory bowel disease may be more sensitive to constipation caused by opioid agonists. Post-operative patients should be monitored for decreased bowel motility. Opioid agonists may obscure the diagnosis or clinical course in patients with acute abdomen. As with other opioid agonists, hydrocodone may cause spasm of the sphincter of Oddi. Hydrocodone should be used with caution in patients with biliary tract disease, including acute pancreatitis.

Acetaminophen; hydrocodone is contraindicated for use in patients with significant respiratory depression and in patients with acute or severe asthma (e.g., status asthmaticus) in unmonitored care settings or in the absence of resuscitative equipment. Receipt of moderate hydrocodone doses in these patients may significantly decrease pulmonary ventilation. Additionally, avoid coadministration with other CNS depressants when possible, as this significantly increases the risk for profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; if concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Monitor patients closely for signs or symptoms of respiratory depression or sedation. In patients with chronic obstructive pulmonary disease (COPD), cor pulmonale, decreased respiratory reserve, hypoxia, hypercapnia, respiratory insufficiency, upper airway obstruction, or preexisting respiratory depression, it is recommended that non-opioid analgesics be considered as alternatives to hydrocodone, as even usual therapeutic doses of hydrocodone may decrease respiratory drive and cause apnea in these patient populations. Extreme caution should also be used in patients with chronic asthma, kyphoscoliosis (a type of scoliosis), hypoxemia, or paralysis of the phrenic nerve. Patients with advanced age, debilitation, or sleep apnea are at an increased risk for the development of respiratory depression associated with hydrocodone. Use with caution in patients with obesity as this is a risk factor for obstructive sleep-apnea syndrome and/or decreased respiratory reserve. Hydrocodone should not be used during impaired consciousness or coma, as significant decreases in respiratory drive may lead to adverse intracranial effects from carbon dioxide retention. Respiratory depression, if left untreated, may cause respiratory arrest and death. Symptoms of respiratory depression include a reduced urge to breathe, a decreased respiratory rate, or deep breaths separated by long pauses (a “sighing” breathing pattern). Carbon dioxide retention from respiratory depression may also worsen opioid sedating effects. Careful monitoring and dose titration is required, particularly when CYP450 3A4 inhibitors or inducers are used concomitantly; concurrent use of a CYP3A4 inhibitor or discontinuation of a concurrently used CYP3A4 inducer may increase plasma hydrocodone concentrations and potentiate the risk of fatal respiratory depression. Management of respiratory depression should include observation, necessary supportive measures, and opioid antagonist use when indicated.

Abrupt discontinuation of prolonged hydrocodone therapy can result in opioid withdrawal symptoms. In patients who have received acetaminophen; hydrocodone around the clock for 5 days or more, gradually reduce the dose by 25% to 50% every 2 to 4 days while monitoring for signs and symptoms of withdrawal. Avoid use of partial agonists (e.g., buprenorphine), mixed agonist/antagonists (e.g., nalbuphine), or pure antagonists (e.g., naloxone) in patients physically dependent on opioids, as an acute withdrawal syndrome may precipitate. The severity of the withdrawal syndrome produced will depend on the degree of physical dependence and on the administered dose of the concomitant drug. If treatment of respiratory depression in an individual physically dependent on opioids is necessary, administer the opioid antagonist with extreme care; titrate the antagonist dose by using smaller than usual doses. In addition, the use of partial agonists or mixed agonist/antagonists in patients who have received or are receiving hydrocodone should be avoided as these medications may reduce the analgesic effect of hydrocodone.

Acetaminophen has been associated with acute liver failure, with some cases resulting in liver transplant and death. Most cases of liver injury are associated with the use of acetaminophen at doses exceeding 4 g per day and often involve the use of more than 1 acetaminophen-containing product. Advise patients receiving acetaminophen to carefully read OTC and prescription labels, to avoid excessive and/or duplicate medications, and to seek medical help immediately if more than 4 g of acetaminophen is ingested in 1 day, even if they feel well. It is important to note that the risk of acetaminophen-induced hepatotoxicity is increased in patients with pre-existing hepatic disease (e.g., hepatitis), those who ingest alcohol (e.g., ethanol intoxication, alcoholism), those with chronic malnutrition, and those with severe dehydration. In patients with chronic hepatic disease, acetaminophen can be used safely in recommended doses and is often preferred to nonsteroidal anti-inflammatory drugs (NSAIDs) due to the absence of platelet impairment, gastrointestinal toxicity, and nephrotoxicity. Though the half-life of acetaminophen may be prolonged, repeated dosing does not result in drug or metabolite accumulation. In addition, cytochrome P450 activity is not increased and glutathione stores are not depleted in hepatically impaired patients taking therapeutic doses, therefore toxic metabolite formation and accumulation is not altered. Although it is always prudent to use the smallest dose of acetaminophen for the shortest duration necessary, courses less than 2 weeks in length have been administered safely to adult patients with stable chronic liver disease. If use acetaminophen in patients with severe hepatic disease, monitor serial liver function tests. Additionally, patients with hepatic impairment may have higher plasma hydrocodone concentrations compared to those with normal hepatic function. Use a low initial dose of acetaminophen; hydrocodone in patients with hepatic impairment, and monitor for sedation and respiratory depression. Consumption of ethanol will result in additive CNS depressant effects. Advise patients to avoid ethanol ingestion and ethanol intoxication, including the ingestion of alcohol contained in prescription or non-prescription medications, during therapy. Patients with alcoholism should be advised of this serious risk, or an alternative medication should be used.

Hydrocodone is an opioid agonist and therefore has abuse potential and risk of fatal overdose from depressed respiration. Addiction may occur in patients who obtain hydrocodone illicitly or in those appropriately prescribed the drug. The risk of addiction in any individual is unknown. However, patients with mental illness (e.g., major depression) or a family history of substance abuse (including alcoholism) have an increased risk of opioid abuse. Assess patients for risks of addiction, abuse, or misuse before drug initiation, and monitor patients who receive opioids routinely for development of these behaviors or conditions. A potential risk of abuse should not preclude appropriate pain management in any patient, but requires more intensive counseling and monitoring. Abuse and addiction are separate and distinct from physical dependence and tolerance; patients with addiction may not exhibit tolerance and symptoms of physical dependence. To discourage abuse, the smallest appropriate quantity of hydrocodone should be dispensed, and proper disposal instructions for unused drug should be given to patients.

Use hydrocodone with caution in patients with CNS depression, toxic psychosis, head trauma, intracranial mass, or increased intracranial pressure. Monitor for signs of drowsiness and depressed respirations, particularly when initiating hydrocodone. Opioids may aggravate such conditions and alter neurologic parameters (e.g., level of consciousness, pupillary responses). Hydrocodone-induced hypoventilation can produce cerebral hypoxia, carbon dioxide retention, and raise CSF pressure. Avoid the use of hydrocodone in patients with impaired consciousness.

Opioid agonists, such as hydrocodone, produce cholinergic side effects (by stimulating medullary vagal nuclei) causing bradycardia and vasovagal syncope, and induce the release of histamine. In patients who are unable to maintain blood pressure due to hypovolemia or dehydration, or in those who concurrently receive other agents that compromise vasomotor tone (e.g., phenothiazines or general anesthetics), opioid agonists may induce peripheral vasodilatation and severe hypotension. These effects can cause problems in patients with cardiac disease (e.g., angina, heart failure). Hydrocodone should be used with caution in patients with cardiac arrhythmias or orthostatic hypotension and should not be used in patients with circulatory shock. Monitor patients for hypotension following hydrocodone initiation and dose titrations.

Acetaminophen; hydrocodone should be used cautiously in patients with renal impairment or renal failure; dosage adjustments may be required. Hydrocodone can cause urinary retention and oliguria, due to increasing the tension of the detrusor muscle. Patients more prone to these effects include those with prostatic hypertrophy, urethral stricture, bladder obstruction, or pelvic tumors. In addition, hydrocodone may accumulate in these patients leading to a prolonged duration of action and potential increase in side effects. Chronic acetaminophen administration should be avoided in patients with underlying renal disease; however it may be used for episodic pain.

Use hydrocodone with caution in geriatric or debilitated patients. Geriatric or debilitated patients are more susceptible to adverse reactions, especially sedation and respiratory depression, probably as a result of altered distribution of the drug or decreased elimination. Initial doses may need to be reduced, and doses should be carefully titrated taking into account analgesic effects, adverse reactions, and concomitant drugs that may depress respiration. According to the Beers Criteria, opiate agonists are considered potentially inappropriate medications (PIMs) in geriatric patients with a history of falls or fractures and should be avoided in these patient populations, with the exception of pain management due to recent fractures or joint replacement, since opiates can produce ataxia, impaired psychomotor function, syncope, and additional falls. If an opiate must be used, consider reducing use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk. Individuals receiving palliative care or those in hospice settings are excluded from the Beers Criteria; the balance of benefits and harms of medication management for these patients may differ from those of the general population of older adults. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). The Guidelines caution that opioids may cause constipation, nausea, vomiting, sedation, lethargy, weakness, confusion, dysphoria, physical and psychological dependency, hallucinations, and unintended respiratory depression, especially in individuals with compromised pulmonary function. These adverse effects can lead to other consequences such as falls. In addition, the initiation of longer-acting opioids is not recommended unless shorter-acting opioids have been unsuccessful, or titration of shorter-acting doses has established a clear daily dose of opioid analgesic that can be provided by using a long-acting form.

Opioid agonists, including acetaminophen; hydrocodone products, are used in children for moderate to severe pain. Acetaminophen; hydrocodone is not indicated for neonates, infants, or children < 2 years of age; and, the safety and efficacy of the tablet and capsule formulations have not been established in pediatric patients. Children weighing < 50 kg may be more sensitive to the effects of opioid agonists and require body weight dosing of opioid agonists.

Patients with G6PD deficiency who overdose with acetaminophen may be at increased risk for drug-induced hemolysis. Practitioners should be aware of this potential complication and monitor at-risk patients for signs and symptoms of hemolysis. Conflicting data exists on whether therapeutic doses of acetaminophen can cause hemolysis in G6PD deficient patients. However, a direct cause and effect relationship has not been well established and therefore, therapeutic doses are generally considered safe in this population.

Symptoms of acute infection (e.g., fever, pain) can be masked during treatment with acetaminophen in patients with bone marrow suppression, especially neutropenia, or immunosuppression.

Any patient receiving acetaminophen; hydrocodone should be warned about the possibility of sedation and to use caution when driving or operating machinery.

Use hydrocodone with caution in patients with adrenal insufficiency (i.e., Addison’s disease), hypothyroidism, or myxedema. Such patients may be at increased risk of adverse events. Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH); however, the thyroid stimulating hormone may be either stimulated or inhibited by opioids. Rarely, adrenal insufficiency has been reported in association with opioid use. Patients should seek immediate medical attention if they experience symptoms such as nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, or hypotension. If adrenocortical insufficiency is suspected, confirm with diagnostic testing as soon as possible. If diagnosed, the patient should be treated with physiologic replacement doses of corticosteroids, and if appropriate, weaned off of opioid therapy. If the opioid can be discontinued, a follow-up assessment of adrenal function should be performed to determine if corticosteroid treatment can be discontinued. Other opioids may be tried; some cases reported use of a different opioid with no recurrence of adrenocortical insufficiency. It is unclear which, if any, opioids are more likely to cause adrenocortical insufficiency. In addition, chronic opioid use may lead to symptoms of hypogonadism, resulting from changes in the hypothalamic-pituitary-gonadal axis. Monitor patients for symptoms of opioid-induced endocrinopathy, particularly those receiving a daily dose equivalent to 100 mg or more of morphine. Patients presenting with signs or symptoms of androgen deficiency should undergo laboratory evaluation.

Like all opioid analgesics, hydrocodone is associated with a significant potential for overdose or poisoning; proper patient selection and counseling is recommended. Hydrocodone should be kept out of the reach of pediatric patients, others for whom the drug was not prescribed, and pets as accidental exposure may cause respiratory failure and a fatal overdose.

Seizures can be precipitated by opioid agonists in patients with a preexisting seizure disorder. The incidence of these effects during hydrocodone therapy is not known, but appears to be rare at normal doses. Monitor patients with a history of seizure disorders for worsened seizure control during therapy.

There are no adequate and well-controlled studies of acetaminophen; hydrocodone in pregnant women. Hydrocodone readily crosses the placenta. Use acetaminophen; hydrocodone during pregnancy only if the potential benefit clearly justifies the potential risk to the fetus. Hydrocodone is not recommended for use in women during and immediately prior to labor and obstetric delivery because oral opioid agonists may cause respiratory depression in the newborn. Opioid analgesics can prolong labor by reducing the strength and frequency of uterine contractions; however, this effect may be offset by an increased rate of cervical dilation. Further, prolonged maternal use of acetaminophen; hydrocodone during pregnancy may result in neonatal opioid withdrawal syndrome (NOWS). This syndrome can be life-threatening. Severe symptoms may require pharmacologic therapy managed by clinicians familiar with neonatal opioid withdrawal. Monitor the neonate for withdrawal symptoms including irritability, hyperactivity, abnormal sleep pattern, high-pitched crying, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity of opioid withdrawal may vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination by the newborn. No overall increase in fetal mortality, as determined by pregnancy outcomes of mothers that overdosed on various amounts of acetaminophen, was apparent in an analysis of 300 women. Treatment with acetylcysteine or methionine did not appear to affect fetal or neonatal toxicity. Of 235 babies exposed to an overdose of only acetaminophen, 168 were normal, 8 had malformations, 16 were spontaneously aborted, and 43 were electively terminated. Of 67 babies exposed to an overdose of a combination acetaminophen product, 51 were normal, 3 had malformations, 2 were spontaneously aborted (late fetal deaths), and 11 were electively terminated. None of the babies with malformations were exposed during the first trimester, but all of the spontaneous abortions and 1 of the late fetal deaths were subsequent to first trimester exposure.

Consider the developmental and health benefits of breast-feeding along with the mother’s clinical need for acetaminophen; hydrocodone and any potential adverse effects on the breast-fed infant from the drugs or the underlying maternal condition. Hydrocodone is distributed into breast milk at varying degrees depending upon the dose. Acetaminophen also crosses into breast milk with a concentration ranging from 0.1% to 1.85% of the maternal dose. A pharmacokinetic study in 30 women receiving acetaminophen; hydrocodone for postpartum pain found that breast fed newborns (postnatal age 3 to 11 days) received a median of 1.6% (range 0.2% to 9%) of the maternal weight-adjusted hydrocodone dosage. The total opiate dosage via breast milk, including the active metabolite hydromorphone, was found to be 0.7% of a therapeutic dosage used for older infants. The authors concluded that doses of hydrocodone given to breast-feeding mothers should be limited to 30 mg/day and doses higher than 40 mg/day should be avoided. As with all opioid-containing products, if acetaminophen; hydrocodone is used by a breast-feeding mother, the infant should be monitored for sedation and respiratory depression. Withdrawal symptoms can occur in breast-fed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. Previous American Academy of Pediatrics (AAP) recommendations considered acetaminophen as usually compatible with breast-feeding. Other alternative analgesics considered to be usually compatible with breast-feeding by the AAP include ibuprofen and morphine; the use of hydrocodone in breast-feeding women was not evaluated by the AAP.

Chronic opioid use may influence the hypothalamic-pituitary-gonadal axis, leading to hormonal changes that may manifest as hypogonadism (gonadal suppression) and pose a reproductive risk. Although the exact causal role of opioids in the clinical manifestations of hypogonadism is unknown, patients could experience libido decrease, impotence, amenorrhea, or infertility. It is not known whether the effects on fertility are reversible. Monitor patients for symptoms of opioid-induced endocrinopathy. Patients presenting with signs or symptoms of androgen deficiency should undergo laboratory evaluation.