Hydrocodone Bitartrate and Acetaminophen 10 mg; 325 mg Tablet, 12-count — NDC 63187-778-12 (Billing 63187-0778-12)

WARNINGS Addiction, Abuse, and Misuse Hydrocodone bitartrate and acetaminophen tablet contains hydrocodone and acetaminophen a Schedule CII controlled substance. As an opioid, hydrocodone bitartrate andacetaminophen tablets exposes users to the risks of addiction, abuse, andmisuse [see DRUG ABUSE AND DEPENDENCE ]. Although therisk of addiction in any individual is unknown, it can occur in patients appropriately prescribed hydrocodone bitartrate and acetaminophen tablets.Addiction can occur at recommended dosages and if the drug is misused orabused.

Assess eachpatient’s risk for opioid addiction, abuse, or misuse prior to prescribing hydrocodone bitartrate and acetaminophen tablets, and monitor all patients receiving hydrocodone bitartrate and acetaminophen tablets for the development of these behaviors or conditions. Risks are increased in patients with a personal or family historyof substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). The potential for these risks should not, however, prevent the proper management of pain in any given patient.

Patients at increased risk may be prescribed opioids such as hydrocodone bitartrate and acetaminophen tablets, but use in such patients necessitates intensive counseling about the risks andproperuse of hydrocodone bitartrate and acetaminophen tablets along with intensive monitoring for signs of addiction, abuse, and misuse. Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing hydrocodone bitartrate and acetaminophen tablets.

Strategies to reduce these risks includeprescribing the drug in the smallest appropriate quantity and advising thepatient on the proper disposal of unused drug [see PRECAUTIONS ; Information for Patients]. Contact local state professional licensing board or statecontrolled substances authority for information on how to prevent and detectabuse or diversion of this product. Hepatotoxicity Acetaminophenhas been associated with cases of acute liver failure, at times resulting inliver transplant and death.

Most of the cases of liver injury are associated withthe use of acetaminophen at doses that exceed 4,000 milligrams per day, andoften involve more than one acetaminophen-containing product. The excessiveintake of acetaminophen may be intentional to cause self-harm or unintentionalas patients attempt to obtain more pain relief or unknowingly take otheracetaminophen-containing products. The riskof acute liver failure is higher in individuals who ingest alcohol while taking acetaminophen.

Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen. Instruct patients to seek medical attention immediately upon ingestion of more than 4,000 milligrams of acetaminophen per day, even if they feel well. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with theuse of opioids, even when used as recommended.

Respiratory depression, if notimmediately recognized and treated, may lead to respiratory arrest and death.Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see OVERDOSAGE ]. Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects ofopioids. While serious, life-threatening, or fatal respiratory depression can occur at anytime during the use of hydrocodone bitartrate and acetaminophen tablets, therisk is greatest during the initiation of therapy or following a dosageincrease.

Monitor patients closely for respiratory depression, especiallywithin the first 24 to 72 hours of initiating therapy with and following dosage increases of hydrocodone bitartrate and acetaminophen tablets. To reduce therisk of respiratory d… [Excerpted — this section continues on DailyMed.]

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. Postmarketing Experience • serotonin syndrome • adrenal insufficiency Androgen Deficiency Chronic useof opioids may influence the hypothalamic-pituitary-gonadal axis, leading toandrogen deficiency that may manifest as symptoms of hypogonadism, such asimpotence, erectile dysfunction, or amenorrhea.

The causal role of opioids inthe syndrome of hypogonadism is unknown because the various medical, physical, lifestyle, and psychological stressors that may influence gonadal hormone levels have not been adequately controlled for in studies conducted to date. Patients presenting with symptoms of androgen deficiency should undergo laboratory evaluation.

Drug Interactions Patients receiving other narcotic analgesics, antihistamines, antipsychotics, antianxiety agents, or other CNS depressants (including alcohol) concomitantlywith hydrocodone bitartrate and acetaminophen tablets may exhibit an additiveCNS depression. When combined therapy is contemplated, the dose of one or bothagents should be reduced. The use of MAO inhibitors or tricyclic antidepressants with hydrocodone preparations may increase the effect of either the antidepressant or hydrocodone.

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 with opioid 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 ]. Benzodiazepines and other Central Nervous System (CNS) Depressants Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants such as alcohol, other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids, can increases the risk of respiratory depression, profound sedation, coma, and death.

Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients closely for signs of respiratory depression and sedation [see WARNINGS ].

Serotonergic Drugs The concomitantuse of opioids with other drugs that affect the serotonergic neurotransmitter system, such as selective serotonin reuptake inhibitors (SSRIs), serotonin andnorepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs),triptans, 5-HT 3 receptor antagonists, drugs that effect theserotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), andmonoamine oxidase (MAO) inhibitors (those intended to treat psychiatricdisorders and also others, such as linezolid and intravenous methylene blue),has resulted in serotonin syndrome [see PRECAUTIONS ; Information for Patients/Caregivers].

If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment. Discontinue hydrocodone bitartrateand acetaminophen tablets if serotonin syndrome is suspected.

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.

Information for Patients/Caregivers Addiction, Abuse, and Misuse Informpatients that the use of hydrocodone bitartrate and acetaminophen tablets, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see WARNINGS ]. Instruct patients not to share hydrocodone bitartrate and acetaminophen tablets with others and to take steps to protect hydrocodone bitartrate and acetaminophen tablets from theft ormisuse. Life-Threatening Respiratory Depression Informpatients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting hydrocodone bitartrate andacetaminophen tablets or when the dosage is increased, and that it can occureven at recommended dosages [see WARNINGS ].

Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop. Accidental Ingestion Inform patients that accidental ingestion, especially by children, may result inrespiratory depression or death [see WARNINGS ]. Instruct patients totake steps to store hydrocodone bitartrate and acetaminophen tablets securely.Opioids are sought by drug abusers and people with addiction disorders and aresubject to criminal diversion.

Consider these risks when prescribing ordispensing hydrocodone bitartrate and acetaminophen tablets. Strategies toreduce these risks include prescribing the drug in the smallest appropriatequantity and advising the patient on the proper disposal of unused drug [see PRECAUTIONS ; Information for Patients ]. Contact local state professional licensing boardor state controlled substances authority for information on how to prevent anddetect abuse or diversion of this product.

Interactions with Benzodiazepines and Other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur if Hydrocodone bitartrate and acetaminophen tablets is used with benzodiazepines or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a health care provider [see WARNINGS and PRECAUTIONS ; Drug Interactions]. Serotonin Syndrome Inform patients that hydrocodone bitartrate and acetaminophen tablets could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs.

Warn patients of the symptoms ofserotonin syndrome and to seek medical attention right away if symptoms develop. Instruct patients to inform their physicians if they are taking, orplan to take serotonergic medications [see PRECAUTIONS ; Error! Hyperlink reference not valid. ].

Adrenal Insufficiency Inform patients that hydrocodone bitartrate and acetaminophen tablets could cause adrenal insufficiency, a potentially life-threatening condition. Adrenal insufficiency may present with non-specific symptoms and signs such as nausea,vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure.Advise patients to seek medical attention if they experience a constellation ofthese symptoms [see WARNINGS ]. Pregnancy Neonatal Opioid Withdrawal Syndrome Inform patients that prolonged use of hydrocodone bitartrate and acetaminophen tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which maybe life-threatening if not recognized and treated [see… [Excerpted — this section continues on DailyMed.]

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… [Excerpted — this section continues on DailyMed.]