ets and cyp3a4 inhibitors, particularly when an inhibitor is added after a stable dose of hydrocodone bitartrate and acetaminophen tablets is achieved [see warnings ]. after stopping a cyp3a4 inhibitor, as the effects of the inhibitor decline, the hydrocodone bitartrate and acetaminophen plasma concentration will decrease [see clinical pharmacology ], resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to hydrocodone bitartrate and acetaminophen tablets. if concomitant use is necessary, consider dosage reduction of hydrocodone bitartrate and acetaminophen tablets until stable drug effects are achieved. monitor patients for respiratory depression and sedation at frequent intervals. if a cyp3a4 inhibitor is discontinued, consider increasing the hydrocodone bitartrate and acetaminophen tablets dosage until stable drug effects are achieved [see dosage and administration ]. monitor for signs of opioid withdrawal. inducer the concomitant use of hydrocodone bitartrate and acetaminophen tablets and cyp3a4 inducers, such as rifampin, carbamazepine, and phenytoin, can decrease the plasma concentration of hydrocodone bitartrate and acetaminophen tablets [see clinical pharmacology ], resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to hydrocodone bitartrate and acetaminophen tablets [see warnings ]. after stopping a cyp3a4 inducer, as the effects of the inducer decline, the hydrocodone bitartrate and acetaminophen tablets plasma concentration will increase [see clinical pharmacology ], which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression. if concomitant use is necessary, consider increasing the hydrocodone bitartrate and acetaminophen tablets dosage until stable drug effects are achieved [see dosage and administration ]. monitor for signs of opioid withdrawal. if a cyp3a4 inducer is discontinued, consider hydrocodone bitartrate and acetaminophen tablets dosage reduction and monitor for signs of respiratory depression. central nervous system depressants due to additive pharmacologic effect, the concomitant use of cns depressants such as alcohol, benzodiazepines and other sedative hypnotics, anxiolytics, and tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. consider dose reduction of one or both drugs. monitor patients for signs of respiratory depression, sedation, and hypotension [see warnings ]. serotonergic drugs the concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as selective serotonin reuptake inhibitors (ssris), serotonin and norepinephrine reuptake inhibitors (snris), tricyclic antidepressants (tcas), triptans, 5-ht3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and monoamine oxidase (mao) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue), has resulted in serotonin syndrome. [see precautions ; information for patients ]. if concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. discontinue hydrocodone bitartrate and acetaminophen tablets if serotonin syndrome is suspected.

potential for these risks should not, however, prevent the proper management of pain in any given patient. patients at increased risk may be prescribed opioids such as hydrocodone bitartrate and acetaminophen tablets, but use in such patients necessitates intensive counseling about the risks and proper use of hydrocodone bitartrate and acetaminophen tablet along with intensive monitoring for signs of addiction, abuse, and misuse. opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. consider these risks when prescribing or dispensing hydrocodone bitartrate and acetaminophen tablets. strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see precautions ; information for patients ]. contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product. life-threatening respiratory depression serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see overdosage ]. carbon dioxide (co2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. while serious, life-threatening, or fatal respiratory depression can occur at any time during the use of hydrocodone bitartrate and acetaminophen tablets, the risk is greatest during the initiation of therapy or following a dosage increase. monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy with and following dosage increases of hydrocodone bitartrate and acetaminophen tablets. to reduce the risk of respiratory depression, proper dosing and titration of hydrocodone bitartrate and acetaminophen tablets are essential [see dosage and administration ]. overestimating the hydrocodone bitartrate and acetaminophen tablets dosage when converting patients from another opioid product can result in a fatal overdose with the first dose. accidental ingestion of even one dose of hydrocodone bitartrate and acetaminophen tablets, especially by children, can result in respiratory depression and death due to an overdose of hydrocodone. neonatal opioid withdrawal syndrome prolonged use of hydrocodone bitartrate and acetaminophen tablets during pregnancy can result in withdrawal in the neonate. neonatal opioid withdrawal syndrome unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. if opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see precautions ; information for patients , pregnancy ] . hepatotoxicity acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 milligrams per day, and often involve more than one acetaminophen containing product. the excessive intake of acetaminophen may be intentional to cause self-harm or unintentional as patients attempt to obtain more pain relief or unknowingly take other acetaminophen-containing products. the risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen. instruct patients to look for acetaminophen or apap on package labels and not to use more than one product that contains acetaminophen. instruct patients to seek medical attention immediately upon ingestion of more than 4000 milligrams of acetaminophen per day, even if they feel well. serious skin reactions rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematous pustulosis (agep), stevens-johnson syndrome (sjs), and toxic epidermal necrolysis (ten), which can be fatal. patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity. hypersensitivity/anaphylaxis there have been post-marketing reports of hypersensitivity and anaphylaxis associated with use of acetaminophen. clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and vomiting. there were infrequent reports of life-threatening anaphylaxis requiring emergency medical attention. instruct patients to discontinue hydrocodone bitartrate and acetaminophen tablets, usp immediately and seek medical care if they experience these symptoms. do not prescribe hydrocodone bitartrate and acetaminophen tablets, usp for patients with acetaminophen allergy. head injury and increased intracranial pressure: the respiratory depressant effects of narcotics and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure. furthermore, narcotics produce adverse reactions which may obscure the clinical course of patients with head injuries. acute abdominal conditions: the administration of narcotics may obscure the diagnosis or clinical course of patients with acute abdominal conditions. risks of concomitant use or discontinuation of cytochrome p450 3a4 inhibitors and inducers concomitant use of hydrocodone bitartrate and acetaminophen tablets with a cyp3a4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of hydrocodone bitartrate and acetaminophen tablets and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression [see warnings ], particularly when an inhibitor is added after a stable dose of hydrocodone bitartrate and acetaminophen tablets is achieved . similarly, discontinuation of a cyp3a4 inducer, such as rifampin, carbamazepine, and phenytoin, in hydrocodone bitartrate and acetaminophen tablet-treated patients may increase hydrocodone bitartrate and acetaminophen tablets plasma concentrations and prolong opioid adverse reactions. when using hydrocodone bitartrate and acetaminophen tablets with cyp3a4 inhibitors or discontinuing cyp3a4 inducers in hydrocodone bitartrate and acetaminophen tablet-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of hydrocodone bitartrate and acetaminophen tablets until stable drug effects are achieved [see precautions ; drug interactions ]. concomitant use of hydrocodone bitartrate and acetaminophen tablets with cyp3a4 inducers or discontinuation of an cyp3a4 inhibitor could decrease hydrocodone bitartrate and acetaminophen tablets plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to hydrocodone bitartrate and acetaminophen tablets. when using hydrocodone bitartrate and acetaminophen tablets with cyp3a4 inducers or discontinuing cyp3a4 inhibitors, monitor patients closely at frequent intervals and consider increasing the opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid withdrawal occur [see precautions ; drug interactions ]. risks due to interactions with central nervous system depressants hypotension, profound sedation, respiratory depression, coma, and death may result if hydrocodone bitartrate and acetaminophen tablets are used concomitantly with alcohol or other central nervous system (cns) depressants (e.g., benzodiazepines and other sedatives/hypnotics, anxiolytics, and tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids). when considering the use of hydrocodone bitartrate and acetaminophen tablets in a patient taking a cns depressant, assess the duration of use of the cns depressant and the patient’s response, including the degree of tolerance that has developed to cns depression. additionally, evaluate the patient’s use of alcohol or illicit drugs that can cause cns depression. if the decision to begin hydrocodone bitartrate and acetaminophen tablets is made, start with a lower dosage of hydrocodone bitartrate and acetaminophen tablets, monitor patients for signs of respiratory depression, sedation, and hypotension, and consider using a lower dose of the concomitant cns depressant [see precautions ; drug interactions ]. life-threatening respiratory depression in patients with chronic pulmonary disease or in elderly, cachectic, or debilitated patients the use of hydrocodone bitartrate and acetaminophen tablets in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated. patients with chronic pulmonary disease: hydrocodone bitartrate and acetaminophen tablet-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of hydrocodone bitartrate and acetaminophen tablets [see warnings ] . elderly, cachectic, or debilitated patients: life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients [see warnings ] . monitor such patients closely, particularly when initiating and titrating hydrocodone bitartrate and acetaminophen tablets and when hydrocodone bitartrate and acetaminophen tablets are given concomitantly with other drugs that depress respiration [see warnings ] . alternatively, consider the use of non-opioid analgesics in these patients. adrenal insufficiency cases of adrenal insufficiency have been reported with opioid use, more often following greater than 1 month of use. presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. if adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. if adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. the information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

is one tablet every four to six hours as needed for pain. the total daily dosage should not exceed 6 tablets. conversion from other opioids to hydrocodone bitartrate and acetaminophen tablets there is inter-patient variability in the potency of opioid drugs and opioid formulations. therefore, a conservative approach is advised when determining the total daily dosage of hydrocodone bitartrate and acetaminophen tablets. it is safer to underestimate a patient’s 24-hour hydrocodone bitartrate and acetaminophen tablets dosage than to overestimate the 24-hour hydrocodone bitartrate and acetaminophen tablets dosage and manage an adverse reaction due to overdose. titration and maintenance of therapy individually titrate hydrocodone bitartrate and acetaminophen tablets to a dose that provides adequate analgesia and minimizes adverse reactions. continually reevaluate patients receiving hydrocodone bitartrate and acetaminophen tablets to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [see warnings ]. frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. if the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the hydrocodone bitartrate and acetaminophen tablets dosage. if unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions. discontinuation of hydrocodone bitartrate and acetaminophen tablets when a patient who has been taking hydrocodone bitartrate and acetaminophen tablets regularly and may be physically dependent no longer requires therapy with hydrocodone bitartrate and acetaminophen tablets, use a gradual downward titration of the dosage to prevent signs and symptoms of withdrawal. do not stop hydrocodone bitartrate and acetaminophen tablets abruptly [see warnings , drug abuse and dependence ].

ed predominantly in patients with chronic overdose. dermatological: skin rash, pruritus. the following adverse drug events may be borne in mind as potential effects of acetaminophen: allergic reactions, rash, thrombocytopenia, agranulocytosis. potential effects of high dosage are listed in the overdosage section. postmarketing experience • serotonin syndrome • adrenal insufficiency androgen deficiency chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiency that may manifest as symptoms of hypogonadism, such as impotence, erectile dysfunction, or amenorrhea. the causal role of opioids in the syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date. patients presenting with symptoms of androgen deficiency should undergo laboratory evaluation.

ets and cyp3a4 inhibitors, particularly when an inhibitor is added after a stable dose of hydrocodone bitartrate and acetaminophen tablets is achieved [see warnings ]. after stopping a cyp3a4 inhibitor, as the effects of the inhibitor decline, the hydrocodone bitartrate and acetaminophen plasma concentration will decrease [see clinical pharmacology ], resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to hydrocodone bitartrate and acetaminophen tablets. if concomitant use is necessary, consider dosage reduction of hydrocodone bitartrate and acetaminophen tablets until stable drug effects are achieved. monitor patients for respiratory depression and sedation at frequent intervals. if a cyp3a4 inhibitor is discontinued, consider increasing the hydrocodone bitartrate and acetaminophen tablets dosage until stable drug effects are achieved [see dosage and administration ]. monitor for signs of opioid withdrawal. inducer the concomitant use of hydrocodone bitartrate and acetaminophen tablets and cyp3a4 inducers, such as rifampin, carbamazepine, and phenytoin, can decrease the plasma concentration of hydrocodone bitartrate and acetaminophen tablets [see clinical pharmacology ], resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to hydrocodone bitartrate and acetaminophen tablets [see warnings ]. after stopping a cyp3a4 inducer, as the effects of the inducer decline, the hydrocodone bitartrate and acetaminophen tablets plasma concentration will increase [see clinical pharmacology ], which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression. if concomitant use is necessary, consider increasing the hydrocodone bitartrate and acetaminophen tablets dosage until stable drug effects are achieved [see dosage and administration ]. monitor for signs of opioid withdrawal. if a cyp3a4 inducer is discontinued, consider hydrocodone bitartrate and acetaminophen tablets dosage reduction and monitor for signs of respiratory depression. central nervous system depressants due to additive pharmacologic effect, the concomitant use of cns depressants such as alcohol, benzodiazepines and other sedative hypnotics, anxiolytics, and tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. consider dose reduction of one or both drugs. monitor patients for signs of respiratory depression, sedation, and hypotension [see warnings ]. serotonergic drugs the concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system, such as selective serotonin reuptake inhibitors (ssris), serotonin and norepinephrine reuptake inhibitors (snris), tricyclic antidepressants (tcas), triptans, 5-ht3 receptor antagonists, drugs that effect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), and monoamine oxidase (mao) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue), has resulted in serotonin syndrome. [see precautions ; information for patients ]. if concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. discontinue hydrocodone bitartrate and acetaminophen tablets if serotonin syndrome is suspected.

te. hydrocodone bitartrate and acetaminophen tablets are not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. opioid analgesics, including hydrocodone bitartrate and acetaminophen tablets, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.

cribed below. hydrocodone : following a 10 mg oral dose of hydrocodone administered to five adult male subjects, the mean peak concentration was 23.6 ± 5.2 ng/ml. maximum serum levels were achieved at 1.3 ± 0.3 hours and the half-life was determined to be 3.8 ± 0.3 hours. hydrocodone exhibits a complex pattern of metabolism including o-demethylation, n-demethylation and 6-ketoreduction to the corresponding 6-α- and 6-β-hydroxymetabolites. see overdosage for toxicity information. acetaminophen : acetaminophen is rapidly absorbed from the gastrointestinal tract and is distributed throughout most body tissues. the plasma half-life is 1.25 to 3 hours, but may be increased by liver damage and following overdosage. elimination of acetaminophen is principally by liver metabolism (conjugation) and subsequent renal excretion of metabolites. approximately 85% of an oral dose appears in the urine within 24 hours of administration, most as the glucuronide conjugate, with small amounts of other conjugates and unchanged drug. see overdosage for toxicity information.

dministration, most as the glucuronide conjugate, with small amounts of other conjugates and unchanged drug. see overdosage for toxicity information.