HYDROCODONE BITARTRATE AND ACETAMINOPHEN

WARNINGS Addiction, Abuse, and Misuse Hydrocodone bitartrate and acetaminophen tablet contains hydrocodone and acetaminophen a Schedule CII controlled substance. As an opioid, hydrocodone bitartrate andacetaminophen tablets exposes users to the risks of addiction, abuse, andmisuse [see DRUG ABUSE AND DEPENDENCE ]. Although therisk of addiction in any individual is unknown, it can occur in patients appropriately prescribed hydrocodone bitartrate and acetaminophen tablets.Addiction can occur at recommended dosages and if the drug is misused orabused. Assess eachpatient’s risk for opioid addiction, abuse, or misuse prior to prescribing hydrocodone bitartrate and acetaminophen tablets, and monitor all patients receiving hydrocodone bitartrate and acetaminophen tablets for the development of these behaviors or conditions. Risks are increased in patients with a personal or family historyof substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The 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 andproperuse of hydrocodone bitartrate and acetaminophen tablets 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 includeprescribing the drug in the smallest appropriate quantity and advising thepatient on the proper disposal of unused drug [see PRECAUTIONS ; Information for Patients]. Contact local state professional licensing board or statecontrolled substances authority for information on how to prevent and detectabuse or diversion of this product. Hepatotoxicity Acetaminophenhas been associated with cases of acute liver failure, at times resulting inliver transplant and death. Most of the cases of liver injury are associated withthe use of acetaminophen at doses that exceed 4,000 milligrams per day, andoften involve more than one acetaminophen-containing product. The excessiveintake of acetaminophen may be intentional to cause self-harm or unintentionalas patients attempt to obtain more pain relief or unknowingly take otheracetaminophen-containing products. The riskof acute liver failure is higher 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 4,000 milligrams of acetaminophen per day, even if they feel well. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with theuse of opioids, even when used as recommended. Respiratory depression, if notimmediately 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 (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects ofopioids. While serious, life-threatening, or fatal respiratory depression can occur at anytime during the use of hydrocodone bitartrate and acetaminophen tablets, therisk is greatest during the initiation of therapy or following a dosageincrease. Monitor patients closely for respiratory depression, especiallywithin the first 24 to 72 hours of initiating therapy with and following dosage increases of hydrocodone bitartrate and acetaminophen tablets. To reduce therisk of respiratory depression, proper dosing and titration of hydrocodonebitartrate and acetaminophen tablets are essential [see DOSAGE AND ADMINISTRATION ]. Overestimating the hydrocodone bitartrate andacetaminophen tablets dosage when converting patients from another opioidproduct can result in a fatal overdose with the first dose. Accidentalingestion of even one dose of hydrocodone bitartrate and acetaminophen tablets,especially by children, can result in respiratory depression and death due toan overdose of hydrocodoneand acetaminophen. Neonatal Opioid Withdrawal Syndrome Prolonged useof hydrocodone bitartrate and acetaminophen tablets during pregnancy can resultin withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlikeopioid withdrawal syndrome in adults, may be life-threatening if not recognizedand treated, and requires management according to protocols developed byneonatology experts. If opioid use is required for a prolonged period in apregnant woman, advise the patient of the risk of neonatal opioid withdrawalsyndrome and ensure that appropriate treatment will be available [see PRECAUTIONS ;Information for Patients, Pregnancy]. Drug Interactions Patientsreceiving other narcotic analgesics, antihistamines, antipsychotics, antianxietyagents, or other CNS depressants (including alcohol) concomitantly withhydrocodone bitartrate and acetaminophen tablets may exhibit an additive CNSdepression. When combined therapy is contemplated, the dose of one or bothagents should be reduced. The use of MAO inhibitors or tricyclicantidepressants with hydrocodone preparations may increase the effect of eitherthe antidepressant or hydrocodone. Drug/Laboratory Test Interactions Acetaminophenmay produce false-positive test results for urinary 5-hydroxyindoleacetic acid. Carcinogenesis, Mutagenesis, Impairment of Fertility Noadequate studies have been conducted in animals to determine whetherhydrocodone or acetaminophen have a potential for carcinogenesis, mutagenesis,or impairment of fertility. Pregnancy Teratogenic Effects PregnancyCategory C Thereare no adequate and well-controlled studies in pregnant women. Hydrocodone bitartrate and acetaminophen tablets should be used during pregnancy only ifthe potential benefit justifies the potential risk to the fetus. Nonteratogenic Effects Babies born to mothers who have been taking opioids regularly prior to delivery will be physically dependent. The withdrawal signs include irritability and excessive crying, tremors, hyperactive reflexes, increased respiratory rate, increased stools, sneezing, yawning, vomiting, and fever. The intensity of the syndrome does not always correlate with the duration of maternal opioid use ordose. There is no consensus on the best method of managing withdrawal. Labor and Delivery Aswith all narcotics, administration of this product to the mother shortly beforedelivery may result in some degree of respiratory depression in the newborn,especially if higher doses are used. Nursing Mothers Acetaminophenis excreted in breast milk in small amounts, but the significance of itseffects on nursing infants is not known. It is not known whether hydrocodone isexcreted in human milk. Because many drugs are excreted in human milk andbecause of the potential for serious adverse reactions in nursing infants fromhydrocodone and acetaminophen, a decision should be made whether to discontinuenursing or to discontinue the drug, taking into account the importance of thedrug to the mother. Pediatric Use Safetyand effectiveness in the pediatric population have not been established. Geriatric Use Clinicalstudies of hydrocodone bitartrate 5 mg and acetaminophen 500 mg did not includesufficient numbers of subjects aged 65 and over to determine whether theyrespond differently from younger subjects. Other reported clinical experiencehas not identified differences in responses between the elderly and youngerpatients. In general, dose selection for an elderly patient should be cautious,usually starting at the low end of the dosing range, reflecting the greaterfrequency of decreased hepatic, renal, or cardiac function, and of concomitantdisease or other drug therapy. Hydrocodoneand the major metabolites of acetaminophen are known to be substantiallyexcreted by the kidney. Thus the risk of toxic reactions may be greater inpatients with impaired renal function due to the accumulation of the parentcompound and/or metabolites in the plasma. Because elderly patients are morelikely to have decreased renal function, care should be taken in doseselection, and it may be useful to monitor renal function. Hydrocodonemay cause confusion and over-sedation in the elderly; elderly patientsgenerally should be started on low doses of hydrocodone bitartrate andacetaminophen tablets and observed closely. Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Hydrocodone bitartrate and acetaminophen tablets with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics,tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone. Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see PRECAUTIONS; Drug Interactions]. If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use. In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response. If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response. Follow patients closely for signs and symptoms of respiratory depression and sedation. Advise both patients and caregivers about the risks of respiratory depression and sedation when Hydrocodone bitartrate and acetaminophen tablet is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advice patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined. Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [see PRECAUTIONS ; Drug Interactions) and PRECAUTIONS ; Information for Patients ]. 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 equipmentis contraindicated. Patientswith Chronic Pulmonary Disease: Hydrocodonebitartrate and acetaminophen tablets-treated patients with significant chronicobstructive pulmonary disease or cor pulmonale, and those with a substantiallydecreased respiratory reserve, hypoxia, hypercapnia, or pre-existingrespiratory depression are at increased risk of decreased respiratory driveincluding apnea, even at recommended dosages of hydrocodone bitartrate andacetaminophen tablets [see WARNINGS ] . Elderly,Cachetic, or Debilitated Patients: Life-threateningrespiratory depression is more likely to occur in elderly, cachectic, ordebilitated patients because they may have altered pharmacokinetics or alteredclearance compared to younger, healthier patients [see WARNINGS]. Monitor suchpatients closely, particularly when initiating and titrating hydrocodonebitartrate and acetaminophen tablets and when hydrocodone bitartrate andacetaminophen tablets is given concomitantly with other drugs that depressrespiration [see WARNINGS ].Alternatively, consider the use ofnon-opioid analgesics in these patients. Adrenal Insufficiency Cases of adrenal insufficiency have beenreported with opioid use, more often following greater than 1 month of use.Presentation of adrenal insufficiency may include non-specific symptoms andsigns including nausea, vomiting, anorexia, fatigue, weakness, dizziness, andlow blood pressure. If adrenal insufficiency is suspected, confirm thediagnosis with diagnostic testing as soon as possible. If adrenal insufficiencyis diagnosed, treat with physiologic replacement doses of corticosteroids. Weanthe patient off of the opioid to allow adrenal function to recover and continuecorticosteroid treatment until adrenal function recovers. Other opioids may betried as some cases reported use of a different opioid without recurrence ofadrenal insufficiency. The information available does not identify anyparticular opioids as being more likely to be associated with adrenal insufficiency.