CONTRAINDICATIONS NORCO is contraindicated in patients with: Significant respiratory depression [see WARNINGS ] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see WARNINGS ] Known or suspected gastrointestinal obstruction, including paralytic ileus [see WARNINGS ] Hypersensitivity to hydrocodone or acetaminophen (e.g., anaphylaxis) [see WARNINGS , ADVERSE REACTIONS ]
WARNINGS Addiction, Abuse, and Misuse NORCO contains hydrocodone, a Schedule II controlled substance. As an opioid,NORCOexposes users to the risks of addiction, abuse, and misuse [see DRUG ABUSE AND DEPENDENCE ]. Although the risk of addiction in any individual is unknown, it can occur in patientsappropriately prescribed NORCO. Addiction can occur at recommended dosages and ifthe drug is misused or abused. Assess each patients risk for opioid addiction, abuse, or misuse prior to prescribing NORCO, and monitor all patients receiving NORCO for the development of thesebehaviors andconditions. Risks are increased in patients with a personal or family history ofsubstance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., majordepression). The potential for these risks should not, however, prevent the proper management ofpain in any given patient. Patients at increased risk may be prescribed opioids such asNORCO, but use in such patients necessitates intensive counseling about the risks andproper use of NORCOalong with intensive monitoring for signs of addiction, abuse,and misuse. Opioids are sought by drug abusers and people with addiction disorders and are subject tocriminal diversion. Consider these risks when prescribing or dispensing NORCO.Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantityand advising the patient on the proper disposal of unused drug [see PRECAUTIONS; Information for Patients ]. Contact local state professional licensing board or state controlledsubstances authority for information on how to prevent and detect abuse or diversion of thisproduct. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use ofopioids, even when used as recommended. Respiratory depression, if not immediatelyrecognized and treated, may lead to respiratory arrest and death. Management of respiratorydepression may include close observation, supportive measures, and use of opioid antagonists,depending on the patients clinical status [see OVERDOSAGE ]. Carbon dioxide (CO2) retentionfrom 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 theuse of NORCO, the risk is greatest during the initiation of therapy or following adosage increase. Monitor patients closely for respiratory depression, especially within the first24-72 hours of initiating therapy with and following dosage increases of NORCO. To reduce the risk of respiratory depression, proper dosing and titration of NORCOisessential [see DOSAGE AND ADMINISTRATION ]. Overestimating the NORCO dosage when converting patients from another opioid product can result in a fatal overdose. Accidental ingestion of NORCO, especially by children, can result inrespiratory depression and death due to an overdose of NORCO. Neonatal Opioid Withdrawal Syndrome Prolonged use of NORCO 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. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see PRECAUTIONS; Information for Patients , Pregnancy ]. Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers Concomitant use of NORCO 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 NORCO Tablets and prolong opioid adverse reactions, and which may cause potentially fatal respiratory depression [see WARNINGS ], particularly when an inhibitor is added after a stable dose of NORCO Tablets is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in NORCO Tablets-treated patients may increase hydrocodone plasma concentrations and prolong opioid adverse reactions. When adding CYP3A4 inhibitors or discontinuing CYP3A4 inducers in NORCO Tablets-treated patients, follow patients at frequent intervals and consider dosage reduction of NORCO Tablets until stable drug effects are achieved [see PRECAUTIONS; Drug Interactions ]. Concomitant use of NORCO Tablets with CYP3A4 inducers or discontinuation of an CYP3A4 inhibitor could decrease hydrocodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to hydrocodone. When using NORCO Tablets with CYP3A4 inducers or discontinuing CYP3A4 inhibitors, follow patients 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 from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use ofNORCO 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 of NORCO Tablets are used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs). Advise 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 , Information for Patients ]. Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients The use of NORCO 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 :NORCO 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 NORCO Tablets [see WARNINGS; Life-Threatening Respiratory Depression ]. Elderly, Cachetic, 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; Life-Threatening Respiratory Depression ] . Follow such patients closely, particularly when initiating and titrating NORCO Tablets and when NORCO Tablets are given concomitantly with other drugs that depress respiration [see WARNINGS; Life-Threatening Respiratory Depression ] . 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 one 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. Severe Hypotension NORCOTablets may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see PRECAUTIONS; Drug Interactions ]. Follow these patients for signs of hypotension after initiating or titrating the dosage of NORCOTablets. In patients with circulatory shock NORCOTablets may cause vasodilatation that can further reduce cardiac output and blood pressure. Avoid the use ofNORCOTablets with circulatory shock. 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 4,000 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 than4,000 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 Therehavebeenpost-marketingreportsofhypersensitivity andanaphylaxisassociatedwiththeuseofacetaminophen.Clinicalsignsincludedswellingof the face,mouth, andthroat, respiratory distress, urticaria, rash, pruritus, and vomiting. Therewereinfrequentreportsof life-threateninganaphylaxis requiring emergency medical attention. Instructpatientsto discontinueNORCOimmediately and seekmedicalcareiftheyexperiencethese symptoms. DonotprescribeNORCOTablets forpatientswith acetaminophenallergy[see PRECAUTIONS;Informationfor Patients/Caregivers ]. Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness In patients who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence ofincreased intracranial pressure or brain tumors), NORCO Tablets may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. Follow such patients for signs of sedation and respiratory depression, particularly when initiating therapy with NORCOTablets. Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of NORCO Tablets in patients with impaired consciousness or coma. Risks of Use in Patients with Gastrointestinal Conditions NORCO Tablets are contraindicated in patients with gastrointestinal obstruction, including paralytic ileus. The administration of NORCO Tablets or other opioids may obscure the diagnosis or clinical course in patients with acute abdominal conditions. Hydrocodone may cause spasm of the sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms. Increased Risk of Seizures in Patients with Seizure Disorders The hydrocodone in NORCO Tablets may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Follow patients with a history of seizure disorders for worsened seizure control duringNORCO tablet therapy. Withdrawal Avoid the use of mixed agonist/antagonist (e.g, pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including NORCO Tablets. In these patients, mixed agonist/antagonist and partial analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms. When discontinuing NORCO Tablets, gradually taper the dosage [see DOSAGE AND ADMINISTRATION ]. Do not abruptly discontinue NORCO [see DRUG ABUSE AND DEPENDENCE ] in patients who have been using NORCO Tablets around the clock for more than 5 days.
DESCRIPTION NORCO (Hydrocodone bitartrate and acetaminophen) is available in tablet form for oral administration. Hydrocodone bitartrate is an opioid analgesic and occurs as fine, white crystals or as a crystalline powder. It is affected by light. The chemical name is 4,5-epoxy-3-methoxy-17-methylmorphinan-6-one tartrate (1:1) hydrate (2:5). It has the following structural formula: Acetaminophen, 4-hydroxyacetanilide, a slightly bitter, white, odorless, crystalline powder, is a non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula: Each NORCO Tablet, 5 mg/325 mg contains: Hydrocodone Bitartrate ...... 5 mg Acetaminophen ................. 325 mg Each NORCO Tablet, 7.5 mg/325 mg contains: Hydrocodone Bitartrate ......... 7.5 mg Acetaminophen ................ 325 mg Each NORCO Tablet, 10 mg/325 mg contains: Hydrocodone Bitartrate .......... 10 mg Acetaminophen .............. 325 mg In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, crospovidone, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch, and stearic acid. Meets USP Dissolution Test 1.
OVERDOSAGE Following an acute overdosage, toxicity may result from hydrocodone or acetaminophen. Clinical Presentation Acute overdosage with NORCOcan be manifested by respiratory depression,somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin,constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial orcomplete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosismay be seen with hypoxia in overdose situations. Acetaminophen Dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect of acetaminophen overdosage. Renal tubular necrosis, hypoglycemic coma and coagulation defects may also occur. Early symptoms following a potentially hepatotoxic overdose may include: nausea, vomiting, diaphoresis and general malaise. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion. Treatment of Overdose Hydrocodone In case of overdose, priorities are the re-establishment of a patent and protected airway andinstitution of assisted or controlled ventilation, if needed. Employ other supportive measures(including oxygen and vasopressors) in the management of circulatory shock and pulmonaryedema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques. The opioid antagonists, naloxone or nalmefene, are specific antidotes to respiratory depressionresulting from opioid overdose. For clinically significant respiratory or circulatory depressionsecondary to NORCOoverdose, administer an opioid antagonist. Opioid antagonistsshould not be administered in the absence of clinically significant respiratory or circulatorydepression secondary to NORCOoverdose. Because the duration of opioid reversal is expected to be less than the duration of action ofNORCOin NORCOtablets, carefully monitor the patient until spontaneousrespiration is reliably re-established. If the response to an opioid antagonist is suboptimal or onlybrief in nature, administer additional antagonist as directed by the products prescribinginformation. In an individual physically dependent on opioids, administration of the recommended usualdosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of thewithdrawal symptoms experienced will depend on the degree of physical dependence and thedose of the antagonist administered. If a decision is made to treat serious respiratory depressionin the physically dependent patient, administration of the antagonist should be initiatedwith careand by titration with smaller than usual doses of the antagonist. Acetaminophen Gastric decontamination with activated charcoal should be administered just prior to N-acetylcysteine (NAC) to decrease systemic absorption if acetaminophen ingestion is known or suspected to have occurred within a few hours of presentation. Serum acetaminophen levels should be obtained immediately if the patient presents 4 hours or more after ingestion to assess potential risk of hepatotoxicity; acetaminophen levels drawn less than 4 hourspost-ingestion may be misleading. To obtain the best possible outcome, NAC should be administered as soon as possible where impending or evolving liver injury is suspected. Intravenous NAC may be administered when circumstances preclude oral administration. Vigorous supportive therapy is required in severe intoxication. Procedures to limit the continuing absorption of the drug must be readily performed since the hepatic injury is dose dependent and occurs early in the course ofintoxication.
PRECAUTIONS Risks of Driving and Operating Machinery NORCO Tablets may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous machinery unless they are tolerant to the effects of NORCO Tablets and know how they will react to the medication [see PRECAUTIONS; Information for Patients/Caregivers ]. Information for Patients Advise the patient to read the FDA-approved patient labeling (Medication Guide). Addiction, Abuse, and Misuse Inform patients that the use of NORCO, even when taken as recommended, can resultin addiction, abuse, and misuse, which can lead to overdose and death [see WARNINGS ].Instruct patients not to share NORCOwith others and to take steps to protectNORCO from theft or misuse. Life-Threatening Respiratory Depression Inform patients of the risk of life-threatening respiratory depression, including information thatthe risk is greatest when starting NORCOor when the dosage is increased, and that itcan occur even at recommended dosages [see WARNINGS ]. Advise patients how to recognizerespiratory depression and to seek medical attention if breathing difficulties develop. Accidental Ingestion Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see WARNINGS ]. Instruct patients to take steps to store NORCO securely and to dispose of unused NORCO by flushing down the toilet. Interactions with Benzodiazepines and Other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur ifNORCO is used withbenzodiazepines and other CNS depressants, including alcohol, andnot to use these concomitantly unless supervised by a healthcare provider [see WARNINGS and PRECAUTIONS; Drug Interactions ]. Serotonin Syndrome Inform patients that NORCOcould cause a rare but potentially life-threateningcondition resulting fromconcomitant administration of serotonergic drugs. Warn patients of thesymptoms of serotonin syndrome and to seek medical attention right away if symptoms develop.Instruct patients to inform their healthcare providersif they are taking, or plan to take serotonergicmedications [see PRECAUTIONS; Drug Interactions ]. Monoamine Oxidase Inhibitor (MAOI) Interaction Inform patients to avoid taking NORCO Tablets while using any drugs that inhibitmonoamine oxidase. Patients should not start MAOIs while taking NORCO Tablets [see PRECAUTIONS; Drug Interactions ]. A drenal Insufficiency Inform patients that NORCOcould cause adrenal insufficiency, a potentially life-threateningcondition. Adrenal insufficiency may present with non-specific symptoms and signssuch as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. Advisepatients to seek medical attention if they experience a constellation of these symptoms [see WARNINGS ]. Important Administration Instructions Instruct patients how to properly take NORCO Tablets [see DOSAGE AND ADMINISTRATION , WARNINGS ]. Maximum Daily Dose of Acetaminophen Inform patients not to take more than 4,000 milligrams of acetaminophen per day. Advise patients to call theirprescriber if they take more than the recommended dose. Hypotension Inform patients that NORCO Tablets may cause orthostatic hypotension andsyncope. Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position) [see WARNINGS ]. Anaphylaxis Inform patients that anaphylaxis has been reported with ingredients contained in NORCO Tablets. Advise patients how to recognize such a reaction and when to seek medical attention[see CONTRAINDICATIONS , ADVERSE REACTIONS ]. Pregnancy Neonatal Opioid Withdrawal Syndrome Inform female patients of reproductive potential that prolonged use of NORCOduring pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated [see WARNINGS , PRECAUTIONS; Pregnancy ]. Embryo-Fetal Toxicity Inform female patients of reproductive potential that NORCOcan cause fetalharm and to inform their healthcare provider of a known or suspected pregnancy [see PRECAUTIONS; Pregnancy ]. Lactation Advise nursing mothers to monitor infants for increased sleepiness (more than usual), breathing difficulties, or limpness. Instruct nursing mothers to seek immediate medical care if they notice these signs [see PRECAUTIONS; Nursing Mothers ]. Infertility Inform patients that chronic use of opioids may cause reduced fertility. It is not known whether these effects on fertility are reversible [see ADVERSE REACTIONS ]. Driving or Operating Heavy Machinery Inform patients that NORCO Tablets may impair the ability to perform potentially hazardous activities such as driving a car or operating heavy machinery. Advise patients not toperform such tasks until they know how they will react to the medication [see WARNINGS ]. Constipation Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [see ADVERSE REACTIONS , CLINICAL PHARMACOLOGY ]. Disposal of Unused NORCO Advise patients to dispose of unused NORCO tablets by flushing unused tablets down the toilet. Laboratory Tests In patients with severe hepatic or renal disease, effects of therapy should be followedwith serial liver and/or renal function tests Drug Interactions Inhibitors of CYP3A4 and CYP2D6 The concomitant use of NORCOand CYP3A4 inhibitors, such as macrolide antibiotics(e.g., erythromycin), azole-antifungal agents (e.g. ketoconazole), and protease inhibitors (e.g.,ritonavir), can increase the plasma concentration ofthe hydrocodone fromNORCO Tablets, resulting in increased orprolonged opioid effects. These effects could be more pronounced with concomitant use ofNORCOand both CYP3A4 and CYP2D6 inhibitors, particularly when an inhibitor is added after a stabledose of NORCO is achieved [see WARNINGS ]. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the NORCOplasma concentration will decrease [see CLINICAL PHARMACOLOGY ], resulting indecreased opioid efficacy or a withdrawal syndrome in patients who had developed physicaldependence to NORCO. If concomitant use is necessary, consider dosage reduction of NORCO until stabledrug effects are achieved. Followpatients for respiratory depression and sedation at frequentintervals. If a CYP3A4 inhibitor is discontinued, consider increasing the NORCO dosage until stable drug effects are achieved.Follow for signs or symptoms of opioid withdrawal. Inducers of CYP3A4 The concomitant use of NORCO and CYP3A4 inducers, such as rifampin,carbamazepine, and phenytoin, can decrease the plasma concentration of NORCO[see CLINICAL PHARMACOLOGY ], resulting in decreased efficacy or onset of a withdrawalsyndrome in patients who have developed physical dependence to NORCO[see WARNINGS ]. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the NORCOplasma concentration will increase [see CLINICAL PHARMACOLOGY ], which couldincrease or prolong both the therapeutic effects and adverse reactions, and may cause seriousrespiratory depression. If concomitant use is necessary, consider increasing the NORCO dosage until stabledrug effects are achieved. Follow the patientfor signs and symptoms ofopioid withdrawal. If a CYP3A4 inducer is discontinued, consider NORCOdosagereduction and followfor signs of respiratory depression. Benzodiazepines and O ther CNS Depressants Due to additive pharmacologic effect, the concomitant use of benzodiazepines and other CNSdepressants, such as benzodiazepinesand other sedativehypnotics, anxiolytics, tranquilizers, musclerelaxants, general anesthetics, antipsychotics, and other opioids, including alcohol, can increase the risk ofhypotension, respiratory depression, profound sedation, coma, and death. Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatmentoptions are inadequate. Limit dosages and durations to the minimum required. Follow patientsclosely for signs of respiratory depression and sedation [see WARNINGS ]. Serotonergic Drugs The concomitant use of opioids with other drugs that affect the serotonergic neurotransmittersystem, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrinereuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptorantagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone,tramadol), and monoamine oxidase (MAO) inhibitors (those intended to treat psychiatricdisorders and also others, such as linezolid and intravenous methylene blue), has resulted inserotonin syndrome [see PRECAUTIONS; Information for Patients ]. If concomitant use is warranted, carefully followthe patient, particularly during treatmentinitiation and dose adjustment. Discontinue NORCO if serotonin syndrome issuspected. Monoamine Oxidase Inhibitors (MAOIs) The concomitant use of opioids and MAOIs, such as phenelzine, tranylcypromine, or linezolid, may manifest as serotonin syndrome, or opioid toxicity (e.g., respiratory depression, coma) [see WARNINGS ]. The use of NORCO is not recommended for patients taking MAOIs or within 14 days of stopping such treatment. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain whileclosely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics The concomitant use of opioids with other opioid analgesics, such as butorphanol, nalbuphine, pentazocine, may reduce the analgesic effect of NORCO and/or precipitate withdrawal symptoms. Advise patient to avoid concomitant use of these drugs. Muscle Relaxants NORCO may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. If concomitant use is warranted, monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of NORCO and/or the muscle relaxant as necessary. Diuretics Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. If concomitant use is warranted, follow patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed. Anticholinergic Drugs The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. If concomitant use is warranted, follow patients for signs and symptoms of urinary retention or reduced gastric motility when NORCO Tablets are used concomitantly with anticholinergicdrugs. Drug/Laboratory Test Interactions Acetaminophen may produce false-positive test results for urinary 5-hydroxyindoleacetic acid. Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis Long-term studies to evaluate the carcinogenic potential of the combination of NORCO Tablets have not been conducted. Long-term studies in mice and rats have been completed by the National Toxicology Program to evaluate the carcinogenic potential of acetaminophen. In 2-year feeding studies, F344/N rats and B6C3F1 mice were fed a diet containing acetaminophen up to 6000 ppm. Female rats demonstrated equivocal evidence of carcinogenicactivity based on increased incidences of mononuclear cell leukemia at 0.8 times the maximum human daily dose (MHDD) of 4 grams/day, based on a body surface area comparison. In contrast, there was no evidence of carcinogenic activity in male rats that received up to 0.7 times or mice at up to 1.2-1.4 times the MHDD, based ona body surface area comparison. Mutagenisis In the published literature, acetaminophen has been reported to be clastogenic when administered at 1500 mg/kg/day to the rat model (3.6-times the MHDD, based on a body surface area comparison). In contrast, noclastogenicity was noted at a dose of 750 mg/kg/day (1.8-times the MHDD, based on a body surface area comparison), suggesting a threshold effect. I m pairment of Fertility In studies conducted by the National Toxicology Program, fertility assessments with acetaminophen have been completed in Swiss CD-1 mice via a continuous breeding study. There were no effects on fertility parameters in mice consuming up to 1.7 times the MHDD of acetaminophen, based on a body surface area comparison. Although there was no effect on sperm motility or sperm density in the epididymis, there was a significant increase in the percentage of abnormal sperm in mice consuming 1.78 times the MHDD (based on a body surface comparison) and there was a reduction in the number of mating pairs producing a fifth litter at this dose,suggesting the potential for cumulative toxicity with chronic administration of acetaminophen near the upper limit of daily dosing. Published studies in rodents report that oral acetaminophen treatment of male animals at doses that are 1.2 times the MHDD and greater (based on a body surface comparison) result in decreased testicular weights, reduced spermatogenesis, reduced fertility, and reduced implantation sites in females given the same doses. These effectsappear to increase with the duration of treatment. The clinical significance of these findings is not known. Infertility Chronic use of opioids may cause reduced fertility in females and males of reproductivepotential. It is not known whether these effects on fertility are reversible [see ADVERSEREACTIONS ]. Pregnancy Teratogenic Effects Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. NORCO Tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nonteratogenic Effects Fetal/Neonatal Adverse Reactions Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes canresult in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortlyafter birth. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity,abnormal sleeppattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight. The onset,duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioidused, duration of use, timing and amount of last maternal use, and rate of elimination of the drugby the newborn. Observe newborns for symptoms of neonatal opioid withdrawal syndrome andmanage accordingly [see WARNINGS ]. Labor or Delivery Opioids cross the placenta and may produce respiratory depression and psycho-physiologiceffects in neonates. An opioid antagonist, such as naloxone, must be available for reversal ofopioid-induced respiratory depression in the neonate. NORCO is not recommendedfor use in pregnant women during or immediately prior to labor, when other analgesic techniquesare more appropriate. Opioid analgesics, including NORCO, can prolong laborthrough actions which temporarily reduce the strength, duration, and frequency of uterinecontractions. However, this effect is not consistent and may be offset by an increased rate ofcervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesicsduring labor for signs of excess sedation and respiratory depression. Nursing Mothers Hydrocodone is present in human milk. The developmental and health benefits of breastfeeding should be considered along with themothers clinical need for NORCO and any potential adverse effects on the breastfedinfant from NORCOor from the underlying maternal condition. Infants exposed to NORCOthrough breast milk should be monitored for excesssedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants whenmaternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped. Pediatric Use Safety and effectiveness of NORCOin pediatric patients have not been established. Geriatric Use Elderly patients (aged 65 years or older) may have increased sensitivity to NORCO. Ingeneral, use caution when selecting a dosage for an elderly patient, usually starting at the lowend of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiacfunction and of concomitant disease or other drug therapy. Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurredafter large initial doses were administered to patients who were not opioid-tolerant or whenopioids were co-administered with other agents that depress respiration. Titrate the dosage ofNORCOslowly in geriatric patients and follow closely for signs of central nervous system and respiratory depression [see WARNINGS ]. Hydrocodone and acetaminophen are known to be substantially excreted by the kidney, and the risk of adversereactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Hepatic Impairment Patients with hepatic impairment may have higher plasma hydrocodone concentrations than those with normal function. Use a low initial dose of NORCO in patients with hepatic impairment and follow closely for adverse events such as respiratory depression and sedation. Renal Impairment Patients with renal impairment may have higher plasma hydrocodone concentrations than those with normal function. Use a low initial dose of NORCO in patients with renal impairment and follow closely for adverse events such as respiratory depression and sedation.
SPL MEDGUIDE SECTION.
Medication Guide NORCO (nor koe) Hydrocodone Bitartrate and Acetaminophen Tablets, USP, CII NORCO is : A strong prescription pain medicine that contains an opioid (narcotic) that is used to manage pain severe enough to require an opioid pain medicine, when other pain treatments such as non-opioid pain medicines do not treat your pain well enough or you cannot tolerate them. An opioid pain medicine that can put you at risk for overdose and death. Even if you take your dose correctly as prescribed you are at risk for opioid addiction, abuse, and misuse that can lead to death. Important information about NORCO : Get emergency help right away if you take too much NORCO (overdose). When you first start taking NORCO when your dose is changed, or if you take too much (overdose), serious or life-threatening breathing problems that can lead to death may occur. Taking NORCO with other opioid medicines, benzodiazepines, alcohol, or other central nervous system depressants (including street drugs) can cause severe drowsiness, decreased awareness, breathing problems, coma, and death. Never give anyone else your NORCO tablets. They could die from taking it. Store NORCO away from children and in a safe place to prevent stealing or abuse. Selling or giving away NORCO tablets is against the law. Do not take NORCO if you have: severe asthma, trouble breathing, or other lung problems. a bowel blockage or have narrowing of the stomach or intestines. known hypersensitivity to hydrocodone or acetaminophen, or any ingredient in hydrocodone and acetaminophen tablets. Before taking NORCO , tell your healthcare provider if you have a history of: head injury, seizures liver, kidney, thyroid problems problems urinating pancreas or gallbladder problems abuse of street or prescription drugs, alcohol addiction, or mental health problems. Tell your healthcare provider if you are: pregnant or planning to become pregnant. Prolonged use of NORCO during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated. b reast feeding. NORCO passes into breast milk and may harm your baby. taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking NORCO with certain other medicines can cause serious side effects that could lead to death. When taking NORCO : Do not change your dose. Take NORCO exactly as prescribed by your healthcare provider.Use the lowest dose possible for the shortest time needed. Take your prescribed dose every four to six hours as needed for pain. Do not take more than your prescribed dose. If you miss a dose, take your next dose at your usual time. Call your healthcare provider if the dose you are taking does not control your pain. If you have been taking NORCO regularly, do not stop taking NORCO without talking to your healthcare provider. After you stop taking NORCO tablets, the unused tablets should be disposed of by flushing down the toilet. While taking NORCO DO NOT: Drive or operate heavy machinery, until you know how NORCO affects you. NORCO can make you sleepy, dizzy, or lightheaded. Drink alcohol or use prescription or over-the-counter medicines that contain alcohol. Using products containing alcohol during treatment with NORCO may cause you to overdose and die. The possible side effects of NORCO : constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness, abdominal pain. Call your healthcare provider if you have any of these symptoms and they are severe. Get emergency medical help if you have: trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue, or throat, extreme drowsiness, light-headedness when changing positions, feeling faint, agitation, high body temperature, trouble walking, stiff muscles, or mental changes such as confusion. These are not all the possible side effects of NORCO. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov For more information call Allergan at 1-800-678-1605 Manufactured by: Warner Chilcott Company, LLC Manati, Puerto Rico 00674 Distributed by: Allergan USA, Inc. Irvine, CA 92612 2017 Allergan. All rights reserved. NORCO is a registered trademark of Allergan Pharmaceuticals International Limited. This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 02/2017
CLINICAL PHARMACOLOGY SECTION.
CLINICAL PHARMACOLOGY Mechanism of Action Hydrocodone is full opioid agonist with relative selectivity for the mu-opioid () receptor, although it can interact with other opioid receptors at higher doses. The principal therapeutic action of hydrocodone is analgesia. Like all full opioid agonists, there is no ceiling effect for analgesia with hydrocodone. Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression. The precise mechanism of the analgesic action is unknown. However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug. The precise mechanism of the analgesic properties of acetaminophen is not established but is thought to involve central actions. Pharmacodynamics Effects on the Central Nervous System The principal therapeutic action of hydrocodone is analgesia. Hydrocodone produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to both increases in carbon dioxide tension and electrical stimulation. Hydrocodone causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings). Marked mydriasis rather than miosis may be seen due to hypoxia in overdose situations. Therapeutic doses of acetaminophen have negligible effects on the cardiovascular or respiratory systems; however, toxic doses may cause circulatory failure and rapid, shallow breathing. Effects on the Gastrointestinal Tract and Other Smooth Muscle Hydrocodone causes a reduction in motility associated with an increase in smooth muscle tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm, resulting in constipation. Other opioid-induced effects may include a reduction in biliary and pancreatic secretions, spasm of sphincter of Oddi, and transient elevations in serum amylase. Effects on the Cardiovascular System Hydrocodone produces peripheral vasodilation which may result in orthostatic hypotension or syncope. Manifestations of histamine release and/or peripheral vasodilation may include pruritus, flushing, red eyes, sweating, and/or orthostatic hypotension. Effects on the Endocrine System Opioids inhibit the secretion of adrenocorticotropic hormone (ACTH), cortisol, and luteinizing hormone (LH) in humans [see ADVERSE REACTIONS ]. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon. Chronic use of opioids may influence the hypothalamic-pituitary-gonadal axis, leading to androgen deficiencythat may manifest as symptoms as low libido, impotence, erectile dysfunction, amenorrhea, or infertility. 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 [see ADVERSE REACTIONS ]. Effects on the Immune System Opioids have been shown to have a variety of effects on components of the immune system. The clinical significance of these findings is unknown. Overall, the effects of opioids appear to be modestlyimmunosuppressive. ConcentrationEfficacy Relationships The minimum effective analgesic concentration will vary widely among patients, especially among patients who have been previously treated with potent agonist opioids. The minimum effective analgesic concentration ofhydrocodone for any individual patient may increase over time due to an increase in pain, the development of anew pain syndrome, and/or the development of analgesic tolerance [see DOSAGE AND ADMINISTRATION ]. ConcentrationAdverse Reaction Relationships There is a relationship between increasing hydrocodone plasma concentration and increasing frequency of dose- related opioid adverse reactions such as nausea, vomiting, CNS effects, and respiratory depression. In opioid- tolerant patients, the situation may be altered by the development of tolerance to opioid-related adverse reactions [see DOSAGE AND ADMINISTRATION ]. Pharmacokinetics The behavior of the individual components is described 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 corresponding6--and 6--hydroxymetabolites. See OVERDOSAGE for toxicity information. CYP3A4 mediated N-demethylation to norhydrocodone is the primary metabolic pathway of hydrocodone with alower contribution from CYP2D6 mediated O-demethylation to hydromorphone. Hydromorphone is formed from the O-demethylation of hydrocodone and may contribute to the total analgesic effect of hydrocodone. Therefore,the formation of these and related metabolites can, in theory, be affected by other drugs [see PRECAUTIONS; Drug Interactions ]. N-demethylation of hydrocodone to form norhydrocodone via CYP3A4 while O-demethylation of hydrocodone to hydromorphone is predominantly catalyzed by CYP2D6 and to a lesser extent by an unknown low affinity CYP enzyme. Hydrocodone and its metabolites are eliminated primarily in thekidneys. Acetaminophen Acetaminophen is rapidly absorbed from the gastrointestinal tract and is distributed throughout mostbody tissues. A small fraction (10-25%) of acetaminophen is bound to plasma proteins. 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. Acetaminophen is primarily metabolized in the liver by first-order kinetics and involves three principal separate pathways: conjugation with glucuronide; conjugation with sulfate; and oxidation via the cytochrome, P450-dependent, mixed-function oxidase enzyme pathway to form a reactive intermediate metabolite, which conjugates with glutathione and is then further metabolized to form cysteine and mercapturic acid conjugates. The principal cytochrome P450 isoenzyme involved appearsto be CYP2E1, with CYP1A2 and CYP3A4 as additional pathways. Approximately 85% of an oral dose appears in the urine within 24 hours of administration, most as the glucuronide conjugate, with smallamounts of other conjugates and unchanged drug. See OVERDOSAGE for toxicity information.
BOXED WARNING SECTION.
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION ; HEPATOTOXICITY ; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Addiction, Abuse, and Misuse NORCO exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patients risk prior to prescribing NORCO , and monitor all patients regularly for the development of these behaviors and conditions [see WARNINGS ]. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of NORCO . Monitor for respiratory depression, especially during initiation of NORCO or following a dose increase [see WARNINGS ]. Accidental Ingestion Accidental ingestion of NORCO , especially by children, can result in a fatal overdose of NORCO [see WARNINGS ]. Neonatal Opioid Withdrawal Syndrome Prolonged use of NORCO during pregnancy can result in neonatal opioid withdrawal syndrome, which 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 WARNINGS ]. Cytochrome P450 3A4 Interaction The concomitant use of NORCO with all C ytochrome P450 3A4 inhibitors may result in an increase in NORCO plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used C ytochrome P450 3A4 inducer may result in an increase in NORCO plasma concentration s . Monitor patients receiving NORCO and any Cytochrome P450 3A4 inhibitor or inducer for signs of respiratory depression or sedation [see CLINICAL PHARMACOLOGY , WARNINGS , PRECAUTIONS; Drug Interactions ]. 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 4 , 000 milligrams per day, and often involve more than one acetaminophen - containing product [see WARNINGS , OVERDOSAGE ]. Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death [see WARNINGS , PRECAUTIONS; Drug Interactions ] Reserve concomitant prescribing of NORCO and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.
PRINCIPAL DISPLAY PANEL NDC 0023-6022-05 NORCO 10/325 Hydrocodone Bitartrate and Acetaminophen Tablets, USP 10 mg/ 325 mg 500 Tablets Rx Only
ADVERSE REACTIONS SECTION.
ADVERSE REACTIONS The following adverse reactions have been identified during post approval use of NORCO. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship todrug exposure. The most frequently reported adverse reactions are light-headedness, dizziness, sedation, nausea and vomiting. Other adverse reactions include: Central Nervous System Drowsiness, mental clouding, lethargy, impairment of mental and physical performance, anxiety, fear, dysphoria, psychological dependence, mood changes. Gastrointestinal System Constipation. Genitourinary System Ureteral spasm, spasm of vesical sphincters, and urinary retention. Special Senses Cases of Hearing impairment or permanent loss have been reported predominately in patients with chronic overdose. Dermatological Skin rash, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, allergicreactions Hematological Thrombocytopenia, agranulocytosis. S e r o t o n i n s yn d r o m e:Casesofserotoninsyndrome, apotentiallylife-threateningcondition,havebeenreported duringconcomitantuseofopioidswithserotonergicdrugs. A d r e n al i n s u ff i c i e n cy:Casesofadrenal insufficiency havebeenreportedwithopioid use,moreoften following greater than onemonthofuse. A n a phy l a x i s:AnaphylaxishasbeenreportedwithingredientscontainedinNORCO A n d r o g e n d ef i c i e n cy:Casesofandrogendeficiencyhaveoccurredwithchronicuseofopioids[see CLINICALPHARMACOLOGY ].
INDICATIONS & USAGE SECTION.
INDICATIONS AND USAGE NORCO is indicated for the management of painsevere enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse, with opioids, even at recommended doses[see WARNINGS ], reserve NORCO for use in patients for whom alternativetreatment options (e.g., non-opioid analgesics): have not been tolerated, or are not expected to be tolerated have not provided adequate analgesia, or are not expected to provide adequate analgesia
DRUG ABUSE AND DEPENDENCE SECTION.
DRUG ABUSE AND DEPENDENCE Controlled Substance NORCOcontains hydrocodone, a Schedule II controlled substance. Abuse NORCOcontainshydrocodone, a substance with a high potential for abuse similarto other opioids including fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, and tapentadol, can be abused and is subject to misuse,addiction, and criminal diversion [see WARNINGS ]. All patients treated with opioids require careful monitoring for signs of abuse and addiction,becauseuse of opioid analgesic products carries the risk of addiction even under appropriatemedical use. Prescription drug abuse is the intentional non-therapeutic use of a prescription drug, even once,for its rewarding psychological or physiological effects. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that developafter repeated substance use and includesa strong desire to take the drug, difficulties incontrolling its use, persisting in its use despite harmful consequences, a higher priority given todrug use than to other activities and obligations, increased tolerance, and sometimes a physicalwithdrawal. Drug-seeking behavior is very common in persons with substance use disorders. Drug-seekingtactics include emergency calls or visits near the end of office hours, refusal to undergoappropriate examination, testing, or referral, repeated loss of prescriptions, tampering withprescriptions, and reluctance to provide prior medical records or contact information for othertreating healthcare provider(s). Doctor shopping (visiting multiple prescribers to obtainadditional prescriptions) is common among drug abusers and people suffering from untreatedaddiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in apatient with poor pain control. Abuse and addiction are separate and distinct from physical dependence and tolerance. Healthcare providers should be aware that addiction may not be accompanied by concurrent toleranceand symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur inthe absence of true addiction. NORCO, like other opioids, can be diverted for non-medical use into illicit channelsof distribution. Careful record-keeping of prescribing information, including quantity, frequency,and renewal requests, as required by state and federal law, is strongly advised. Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy,and proper dispensing and storage are appropriate measures that help to limit abuse of opioiddrugs. Risks Specific to Abuse of NORCO NORCOis for oral use only. NORCOposes a risk of overdose and death. The risk is increased with concurrent abuse of NORCOwith alcohol and other central nervous system depressants. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV. Dependence Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance isthe need for increasing doses of opioids to maintain a defined effect such as analgesia (in theabsence of disease progression or other external factors). Tolerance may occur to both thedesired and undesired effects of drugs, and may develop at different rates for different effects. Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significantdosage reduction of a drug. Withdrawal also may be precipitated through the administration ofdrugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonistanalgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physicaldependence may not occur to a clinically significant degree until after several days to weeks ofcontinued opioid usage. NORCOshould not be abruptly discontinued in a physically-dependent patient [see DOSAGE AND ADMINISTRATION ]. If NORCOis abruptly discontinued in a physicallydependentpatient, a withdrawal syndrome may occur. Some or all of the following cancharacterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills,myalgia, and mydriasis. Other signs and symptoms also may develop, including irritability,anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia,vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate. Infants born to mothers physically dependent on opioids will also be physically dependent andmay exhibit respiratory difficulties and withdrawal signs [see PRECAUTIONS; Pregnancy ].
DOSAGE & ADMINISTRATION SECTION.
DOSAGE AND ADMINISTRATION Important Dosage and Administration Instructions Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see WARNINGS ]. Initiate the dosing regimen for each patient individually, taking into account the patient's severityof pain, patient response, prior analgesic treatment experience, and risk factors for addiction,abuse, and misuse [see WARNINGS ]. Followpatients closely for respiratory depression, especially within the first 24-72 hours ofinitiating therapy and following dosage increases with NORCO and adjust the dosageaccordingly [see WARNINGS ]. Initial Dosage Initiating Treatment with NORCO NORCO 5/325 The usual adult dosage is one or two tablets every four to six hours as needed for pain. The total daily dosage should not exceed 8 tablets. NORCO 7.5/325 NORCO 10/325 The usual adult dosage 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 NORCO 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 ofNORCO. It is safer to underestimate a patients 24-hour NORCO dosagethan to overestimate the 24-hour NORCO dosage and manage an adverse reaction due to overdose. Conversion from NORCO to Extended-Release Hydrocodone The relative bioavailability of hydrocodone from NORCO compared to extended-release hydrocodone products is unknown, so conversion to extended-release products must be accompanied by close observation for signs of excessive sedation and respiratory depression. Titration and Maintenance of Therapy Individually titrate NORCO to a dose that provides adequate analgesia and minimizesadverse reactions. Continually reevaluate patients receiving NORCO to assess themaintenance of pain control and the relative incidence of adverse reactions, as well asmonitoring for the development of addiction, abuse, or misuse [see WARNINGS ]. Frequentcommunication is important among the prescriber, other members of the healthcare team, thepatient, and the caregiver/family during periods of changing analgesic requirements, includinginitial titration. If the level of pain increases after dosage stabilization, attempt to identify the source of increasedpain before increasing the NORCO dosage. If unacceptable opioid-related adversereactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriatebalance between management of pain and opioid-related adverse reactions. Discontinuation of NORCO When a patient who has been taking NORCO regularly and may be physicallydependent no longer requires therapy with NORCO, taperthe dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms ofwithdrawal. If the patient develops these signs or symptoms, raise the dose to the previous level and taper moreslowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both. Do not abruptly discontinueNORCO ina physically-dependent patient [see WARNINGS , DRUG ABUSE AND DEPENDENCE ].
HOW SUPPLIED SECTION.
HOW SUPPLIED NORCO is supplied as: NORCO 5/325 capsule-shaped, white tablets bisected on one side and debossed with NORCO 071 on the other side. Each tablet contains 5 mg hydrocodone bitartrate and 325 mg acetaminophen. They are supplied in bottles of 100 (NDC 0023-6002-01). NORCO 7.5/325 capsule-shaped, white tablets bisected on one side and debossed with NORCO 729 on the other side. Each tablet contains 7.5 mg hydrocodone bitartrate and 325 mg acetaminophen. They are supplied in bottles of 100 (NDC 0023-6021-01) and 500 (NDC0023-6021-05). NORCO 10/325 capsule-shaped, white tablets bisected on one side and debossed with NORCO 539 on the other side. Each tablet contains 10 mg hydrocodone bitartrate and 325 mg acetaminophen. They are supplied in bottles of 100 (NDC 0023-6022-01) and 500 (NDC 0023-6022-05). Store at 20 to 25C (68 to 77F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP with a child-resistant closure. Distributed by: Allergan USA, Inc. Irvine, CA 92612 2017Allergan. All rights reserved. NORCO is a registered trademark of Allergan PharmaceuticalsInternational Limited. Revised: 02/2017