DESCRIPTION

Hydrocodone bitartrate and acetaminophen is supplied in tablet form for oral administration.

Hydrocodone bitartrate is an opioid analgesic and antitussive and occurs as fine, white crystals or as a crystalline powder. It is affected by light. The chemical name is: 4,5α-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:

Hydrocodone bitartrate and acetaminophen tablets USP, for oral administration, are available in a variety of strengths as described in the following table.

Each hydrocodone bitartrate and acetaminophen tablet contains:

Strength	Hydrocodone Bitartrate	Acetaminophen
5 mg/325 mg        7.5 mg/325 mg          10 mg/325 mg	5 mg 7.5 mg 10 mg	325 mg 325 mg 325 mg

In addition each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, crospovidone, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch and stearic acid.

Meets USP Dissolution Test 1.

CLINICAL PHARMACOLOGY

Hydrocodone is a semisynthetic narcotic analgesic and antitussive with multiple actions qualitatively similar to those of codeine. Most of these involve the central nervous system and smooth muscle. The precise mechanism of action of hydrocodone and other opiates is not known, although it is believed to relate to the existence of opiate receptors in the central nervous system. In addition to analgesia, narcotics may produce drowsiness, changes in mood and mental clouding.

The analgesic action of acetaminophen involves peripheral influences, but the specific mechanism is as yet undetermined. Antipyretic activity is mediated through hypothalamic heat regulating centers. Acetaminophen inhibits prostaglandin synthetase. Therapeutic doses of acetaminophen have negligible effects on the cardiovascular or respiratory systems; however, toxic doses may cause circulatory failure and rapid, shallow breathing.

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-keto reduction to the corresponding 6-α- and 6-β-hydroxy-metabolites. 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.

INDICATIONS AND USAGE

Hydrocodone bitartrate and acetaminophentablets are indicated for the management of relief of moderate to moderatelysevere pain, pain severe enough to require an opioid analgesic and for whichalternative treatments are inadequate.

Limitations of Use
Because of the risks of addiction, abuse, andmisuse, with opioids, even at recommended doses [see WARNINGS], reserve hydrocodonebitartrate and acetaminophen tablets 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

CONTRAINDICATIONS

Hydrocodonebitartrate and acetaminophen tablets are 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]

•

Hypersensitivity to hydrocodone or acetaminophen

•

Hypersensitive to other opioids which may exhibit cross-sensitivity to hydrocodone

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 (CO2) 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 [seePRECAUTIONS;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 [seePRECAUTIONS; 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.

PRECAUTIONS

General

Special Risk Patients

As with any narcotic analgesic agent, hydrocodonebitartrate and acetaminophen tablets should be used with caution in elderly ordebilitated patients and those with severe impairment of hepatic or renalfunction, hypothyroidism, Addison’s disease, prostatic hypertrophy or urethralstricture. The usual precautions should be observed and the possibility of respiratorydepression should be kept in mind.

Cough Reflex

Hydrocodone suppresses the cough reflex;as with all narcotics, caution should be exercised when hydrocodone bitartrateand acetaminophen tablets are used postoperatively and in patients with pulmonarydisease. 

ADVERSE REACTIONS

The most frequently reported adverse reactions include: lightheadedness, dizziness, sedation, nausea and vomiting. These effects seem to be more prominent in ambulatory than in nonambulatory patients and some of these adverse reactions may be alleviated if the patient lies down. 

Other adverse reactions include 
 
Central Nervous System 

Drowsiness, mental clouding, lethargy, impairment of mental and physical performance, anxiety, fear, dysphoria, psychic dependence, mood changes. 

Gastrointestinal System 

Prolonged administration of hydrocodone bitartrate and acetaminophen tablets may produce constipation.

Genitourinary System 

Ureteral spasm, spasm of vesical sphincters and urinary retention have been reported with opiates. 

Respiratory Depression 

Hydrocodone bitartrate may produce dose-related respiratory depression by acting directly on the brain stem respiratory center. (see OVERDOSAGE). 

Special Senses 

Cases of hearing impairment or permanent loss have been reported 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.

DRUG ABUSE AND DEPENDENCE

Controlled  Substance

Hydrocodone  bitartrate and acetaminophen tablets contains hydrocodone and acetaminophen, aSchedule CII controlled substance.

Abuse

Hydrocodone  bitartrate and acetaminophen tablets contains hydrocodone and acetaminophen, asubstance with a high potential for abuse similar to other opioids including  withdrawal also may be precipitated through the administration of drugs withopioid antagonist activity (e.g., naloxone, nalmefene), mixedagonist/antagonist analgesics (pentazocine, butorphanol, nalbuphine), orpartial agonists (buprenorphine). Physical dependence may not occur to aclinically significant degree until after several days to weeks of continuedopioid usage. Hydrocodone bitartrate and acetaminophen tablets can be abusedand is subject to misuse, addiction, and criminal diversion [see WARNINGS].

All patients  treated with opioids require careful monitoring for signs of abuse and  addiction, since use of opioid analgesic products carries the risk of addiction  even under appropriate medical use.

Prescription  drug abuse is the intentional non-therapeutic use of a prescription drug, evenonce, for its rewarding psychological or physiological effects.

Drug  addiction is a cluster of behavioral, cognitive, and physiological phenomenathat develop after repeated substance use and includes: a strong desire to take  the drug, difficulties in controlling its use, persisting in its use despite  harmful consequences, a higher priority given to drug use than to other  activities and obligations, increased tolerance, and sometimes a physical  withdrawal.

“Drug-seeking”behavior is very common in persons with substance use disorders. Drug-seeking  tactics include emergency calls or visits near the end of office hours, refusal  to undergo appropriate examination, testing, or referral, repeated “loss” of  prescriptions, tampering with prescriptions and reluctance to provide priormedical records or contact information for other treating health careprovider(s). “Doctor shopping” (visiting multiple prescribers) to obtainadditional prescriptions is common among drug abusers and people suffering from  untreated addiction. Preoccupation with achieving adequate pain relief can beappropriate behavior in a patient with poor pain control.

Abuse and  addiction are separate and distinct from physical dependence and tolerance.Health care providers should be aware that addiction may not be accompanied by  concurrent tolerance and symptoms of physical dependence in all addicts. Inaddition, abuse of opioids can occur in the absence of true addiction.

Hydrocodone  bitartrate and acetaminophen tablets, like other opioids, can be diverted fornon-medical use into illicit channels of distribution. Careful record-keepingof prescribing information, including quantity, frequency, and renewalrequests, as required by state and federal law, is strongly advised. Properassessment of the patient, proper prescribing practices, periodic re-evaluationof therapy, and proper dispensing and storage are appropriate measures thathelp to limit abuse of opioid drugs.

Risks  Specific to Abuse of Hydrocodone Bitartrate and Acetaminophen Tablets

Hydrocodone

Serious  overdose with hydrocodone is characterized by respiratory depression (adecrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration,cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscleflaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. Insevere overdosage, apnea, circulatory collapse, cardiac arrest and death mayoccur.

Acetaminophen

In  acetaminophen overdosage: dose-dependent, potentially fatal hepatic necrosis isthe most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, andcoagulation defects may also occur.

Early  symptoms following a potentially hepatotoxic overdose may include: nausea,vomiting, diaphoresis and general malaise. Clinical and laboratory evidence ofhepatic toxicity may not be apparent until 48 to 72 hours post-ingestion.

Treatment

A single or multiple drug overdose with hydrocodone and acetaminophen is a potentially  lethal  polydrug overdose, and consultation with a regional poison control  center is recommended. Immediate treatment includes support of  cardiorespiratory function and measures to reduce drug absorption. Oxygen,  intravenous fluids, vasopressors, and other supportive measures should beemployed as indicated. Assisted or controlled ventilation should also beconsidered.

For  hydrocodone overdose, primary attention should be given to the reestablishment  of adequate respiratory exchange through provision of a patent airway and the  institution of assisted or controlled ventilation. The narcotic antagonistnaloxone hydrochloride is a specific antidote against respiratory depressionwhich may result from overdosage or unusual sensitivity to narcotics, includinghydrocodone. Since the duration of action of hydrocodone may exceed that of theantagonist, the patient should be kept under continued surveillance, andrepeated doses of the antagonist should be administered as needed to maintainadequate respiration. A narcotic antagonist should not be administered in theabsence of clinically significant respiratory or cardiovascular depression.

Gastricdecontamination with activated charcoal should be administered just prior toN-acetylcysteine (NAC) to decrease systemic absorption if acetaminophen isknown or suspected to have occurred within a few hours of presentation. Serumacetaminophen levels should be obtained immediately if the patient presents 4hours or more after ingestion to assess potential risk of hepatotoxicity;acetaminophen levels drawn less than 4 hours post-ingestion may be misleading.To obtain the best possible outcome, NAC should be administered as soon aspossible where impending or evolving liver injury is suspected. Intravenous NACmay be administered when circumstances preclude oral administration.

Vigoroussupportive therapy is required in severe intoxication. Procedures to limit thecontinuing absorption of the drug must be readily performed since the hepaticinjury is dose-dependent and occurs early in the course of intoxication.

Dependence

Bothtolerance and physical dependence can develop during chronic opioid therapy.Tolerance is the need for increasing doses of opioids to maintain a definedeffect such as analgesia (in the absence of disease progression or otherexternal factors). Tolerance may occur to both the desired and undesiredeffects of drugs, and may develop at different rates for different effects.Physical dependence results in withdrawal symptoms after abrupt discontinuationor a significant dosage reduction of a drug. Withdrawal also may beprecipitated through the administration of drugs with opioid antagonistactivity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics(pentazocine, butorphanol, nalbuphine), or partial agonists (buprenorphine).Physical dependence may not occur to a clinically significant degree untilafter several days to weeks of continued opioid usage.

Hydrocodonebitartrate and acetaminophen tablets should not be abruptly discontinued [see DOSAGE AND ADMINISTRATION]. If hydrocodone bitartrate and acetaminophentablets is abruptly discontinued in a physically dependent patient, awithdrawal syndrome may occur. Some or all of the following can characterizethis syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration,chills, myalgia, and mydriasis. Other signs and symptoms also may develop,including: irritability, anxiety, backache, joint pain, weakness, abdominalcramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased bloodpressure, respiratory rate, or heart rate.

Infants bornto mothers physically dependent on opioids will also be physically dependentand may exhibit respiratory difficulties and withdrawal signs [see PRECAUTIONS;Error! Hyperlink reference not valid.].

OVERDOSAGE

Clinical  Presentation

Acuteoverdose with hydrocodone bitartrate and acetaminophen tablets can bemanifested by respiratory depression, somnolence progressing to stupor or coma,skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, insome cases, pulmonary edema, bradycardia, hypotension, partial or completeairway obstruction, atypical snoring, and death. Marked mydriasis rather thanmiosis may be seen with hypoxia in overdose situations.

Treatment  of Overdose

In case ofoverdose, priorities are the reestablishment of a patent and protected airwayand institution of assisted or controlled ventilation, if needed. Employ othersupportive measures (including oxygen and vasopressors) in the management ofcirculatory shock and pulmonary edema as indicated. Cardiac arrest orarrhythmias will require advanced life-support techniques.

The opioidantagonists, naloxone or nalmefene, are specific antidotes to respiratorydepression resulting from opioid overdose. For clinically significantrespiratory or circulatory depression secondary to hydrocodone bitartrate andacetaminophen tablets overdose, administer an opioid antagonist. Opioidantagonists should not be administered in the absence of clinically significantrespiratory or circulatory depression secondary to hydrocodone bitartrate andacetaminophen tablets overdose.

Because theduration of opioid reversal is expected to be less than the duration of actionof hydrocodone bitartrate and acetaminophen tablets in hydrocodone bitartrateand acetaminophen tablets, carefully monitor the patient until spontaneousrespiration is reliably re-established. If the response to an opioid antagonistis suboptimal or only brief in nature, administer additional antagonist asdirected by the product’s prescribing information.

In anindividual physically dependent on opioids, administration of the recommendedusual dosage of the antagonist will precipitate an acute withdrawal syndrome.The severity of the withdrawal symptoms experienced will depend on the degreeof physical dependence and the dose of the antagonist administered. If adecision is made to treat serious respiratory depression in the physicallydependent patient, administration of the antagonist should be begun with careand by titration with smaller than usual doses of the antagonist.

DOSAGE AND ADMINISTRATION

Important  Dosage and Administration Instructions

Initiate thedosing regimen for each patient individually, taking into account the patient'sseverity of pain, patient response, prior analgesic treatment experience, andrisk factors for addiction, abuse, and misuse [see WARNINGS].

Monitorpatients closely for respiratory depression, especially within the first 24 to 72hours of initiating therapy and following dosage increases with hydrocodonebitartrate and acetaminophen tablets and adjust the dosage accordingly [see WARNINGS].

Dosage should be adjusted according tothe severity of the pain and the response of the patient. However, it should bekept in mind that tolerance to hydrocodone can develop with continued use andthat the incidence of untoward effects is dose related.

Initial Dosage Treatment with Hydrocodone Bitartrate and Acetaminophen Tablets

The usual adult dosageis one tablet every four to six hours as needed for pain. The total dailydosage should not exceed 6 tablets.

5 mg/325 mg	The usual adult dosage is one or two tablets every four to six hours as needed for pain.
7.5 mg/325 mg	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.
10 mg/325 mg	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.

Titrationand Maintenance of Therapy

Individually titrate hydrocodonebitartrate and acetaminophen tablets to a dose that provides adequate analgesiaand minimizes adverse reactions. Continually reevaluate patients receiving hydrocodonebitartrate and acetaminophen tablets to assess the maintenance of pain controland the relative incidence of adverse reactions, as well as monitoring for thedevelopment of addiction, abuse, or misuse [see WARNINGS]. Frequentcommunication is important among the prescriber, other members of thehealthcare team, the patient, and the caregiver/family during periods ofchanging analgesic requirements, including initial titration.

If the levelof pain increases after dosage stabilization, attempt to identify the source ofincreased pain before increasing the hydrocodone bitartrate and acetaminophentablets dosage. If unacceptable opioid-related adverse reactions are observed,consider reducing the dosage. Adjust the dosage to obtain an appropriatebalance between management of pain and opioid-related adverse reactions.

Discontinuation  of Hydrocodone Bitartrate and Acetaminophen Tablets

When apatient who has been taking hydrocodone bitartrate and acetaminophen tabletsregularly and may be physically dependent no longer requires therapy with hydrocodonebitartrate and acetaminophen tablets, use a gradual downward titration of thedosage to prevent signs and symptoms of withdrawal. Do not stop hydrocodonebitartrate and acetaminophen tablets abruptly [see WARNINGS, DRUG ABUSE ANDDEPENDENCE].

HOW SUPPLIED

Hydrocodone Bitartrate and Acetaminophen Tablets USP are available in the following strengths:


Hydrocodone Bitartrate and Acetaminophen Tablet USP, 10 mg/325 mg is available as white to off-white, oval shaped tablets, debossed with “U03” on one side and break-line on the other side. Each tablet contains 10 mg hydrocodone bitartrate and 325 mg acetaminophen.

         Bottles of 12                 NDC 63187-778-12
         Bottles of 15                NDC 63187-778-15

         Bottles of 20                NDC 63187-778-20
         Bottles of 30                NDC 63187-778-30

         Bottles of 60              NDC 63187-778-60
         Bottles of 90                NDC 63187-778-90

Storage: Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] 

Dispense in a tight, light-resistant container as defined in the USP with a child-resistant closure. Keep this and all medication out of the reach of children.

A Schedule C-II controlled drug substance.

Dispense with Medication Guide available at www.aurobindousa.com/product-medication-guides

 Manufactured by:
Aurolife Pharma LLC
Dayton, NJ 08810 

Manufactured for:
Aurobindo Pharma USA, Inc.
Dayton, NJ 08810 

Repackaged by:
Proficient Rx LP.
Thousand Oaks, CA 91320 

Revised: 09/2016

MEDICATION GUIDE

Hydrocodone Bitartrate and Acetaminophen Tablets, USP CII

HIGH-droe-KOE-dohnby-TAR-trate/ass-eet-ah-MEE-noe-fen

Hydrocodone Bitartrate and Acetaminophen Tablets are:

•

A strong prescription pain medicine that contains an opioid (narcotic) that is used for the management of relief of moderate to moderately severe pain, pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate or when 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 Hydrocodone Bitartrate and Acetaminophen Tablets:

•

Get emergency help right away if you take too much hydrocodone bitartrate and acetaminophen tablets (overdose). When you first start taking hydrocodone bitartrate and acetaminophen tablets, 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 hydrocodone bitartrate and acetaminophen tablets 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 hydrocodone bitartrate and acetaminophen tablets. They could die from taking it. Store hydrocodone bitartrate and acetaminophen tablets away from children and in a safe place to prevent stealing or abuse. Selling or giving away hydrocodone bitartrate and acetaminophen tablets is against the law.

Do not take Hydrocodone Bitartrate and Acetaminophen Tablets if you have:

•

acute or severe bronchial asthma, trouble breathing, or other lung problems. 

•

a bowel blockage or have narrowing of the stomach or intestines.

•

significant respiratory depression 

•

severe impairment of hepatic or renal function, hypothyroidism, Addison’s disease, prostatic hypertrophy or urethral stricture

Before  taking Hydrocodone Bitartrate and Acetaminophen Tablets, tell your healthcareprovider 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 hydrocodone bitartrate and acetaminophen tablets during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated. 

•

breastfeeding. Hydrocodone bitartrate and acetaminophen tablets passes into breast milk and may harm your baby.

•

taking prescription or over-the-counter medicines, vitamins, or herbal supplements. Taking hydrocodone bitartrate and acetaminophen tablets with certain other medicines can cause serious side effects that could lead to death.

Whentaking Hydrocodone Bitartrate and Acetaminophen Tablets:     

•

Do not change your dose. Take hydrocodone bitartrate and acetaminophen tablets exactly as prescribed by your healthcare provider. 

•

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. 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 hydrocodone bitartrate and acetaminophen tablets regularly, do not stop taking hydrocodone bitartrate and acetaminophen tablets without talking to your healthcare provider.

•

After you stop taking hydrocodone bitartrate and acetaminophen tablets, 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. 

While  taking Hydrocodone Bitartrate and Acetaminophen Tablets DO NOT:

•

Drive or operate heavy machinery, until you know how hydrocodone bitartrate and acetaminophen tablets affects you. Hydrocodone bitartrate and acetaminophen tablets 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 hydrocodone bitartrate and acetaminophen tablets may cause you to overdose and die.

The  possible side effects of hydrocodone Bitartrate and Acetaminophen Tablets:

•

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.

General Information about Hydrocodone Bitartrate and Acetaminophen Tablets

Medicinesare sometimes prescribed for purposes other than those listed in a MedicationGuide. Do not use hydrocodonebitartrate and acetaminophen tablets for a conditionfor which it was not prescribed. Do not give hydrocodone bitartrate andacetaminophen tablets to other people even if theyhave the same condition, they may harm them.

These are notall the possible side effects of hydrocodone bitartrate and acetaminophentablets. Call your doctor for medical advice about side effects. You may alsorequest medical information or to report suspected adverse reactions, contactAurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088. Formore information go to dailymed.nlm.nih.gov

What are the ingredients in Hydrocodone Bitartrate andAcetaminophen Tablets?

Active Ingredients: hydrocodone bitartrate and acetaminophen

Inactive ingredients: colloidal silicon dioxide, croscarmellose sodium,crospovidone, magnesium stearate, microcrystalline cellulose, povidone,pregelatinized starch and stearic acid.

ThisMedication Guide has been approved by the U.S. Food and Drug Administration.

Manufacturedby:
AurolifePharma LLC
Dayton, NJ08810

Manufacturedfor:
AurobindoPharma USA, Inc.
Dayton, NJ 08810 

Repackaged by:
Proficient Rx LP.
Thousand Oaks, CA 91320 

Revised:09/2016

       

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 10 mg/325 mg (30 Tablet Bottle)

NDC 63187-778-30
Hydrocodone Bitartrate and
Acetaminophen Tablets, USP CII
10 mg/325 mg
Rx only             30 Tablets