Hydrocodone/APAP

Hydrocodone Bitartrate and Acetaminophen Tablet is indicated for the management of pain severe 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, which can occur at dosage or duration [see WARNINGS], reserve Hydrocodone Bitartrate and Acetaminophen Tablets for use in patients for whom alternative treatment 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 Hydrocodone Bitartrate and Acetaminophen Tablets should not be used for an extended period of time unless the pain remains severe enough to require an opioid analgesic and for which alternative treatment options continue to be inadequate.

Important Dosage and Administration Instructions Hydrocodone Bitartrate and Acetaminophen Tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opiods and how to mitigate the associated risks. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see WARNINGS]. Because the risk of overdose increases as opiod doses increase, reserve titration to higher doses of Hydrocodone Bitartrate and Acetaminophen Tablets for patients in who, lower doses are insufficiently effective and in who, the expected benefits of using a higher dose opiod clearly outweigh the substantial risks. Many acute pain conditions (e.g., the pain that occurs with a number of surgical procedures or acute musculoskeletal injuries) require no more than a few days of an opioid analgesic. Clinical guidelines on opioid prescribing for some acute pain conditions are available. There is variability in the opioid analgesic dose and duration needed to adequately manage pain due both to the cause of pain and to individual patient factors. Initiate the dosing regimen for each patient individually, taking into account the patient’s underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see WARNINGS]. Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with Hydrocodone Bitartrate and Acetaminophen Tablets. Consider this risk when selecting an initial dose and when making dose adjustments [see WARNINGS]. Initial Dosage Use of Hydrocodone Bitartrate and Acetaminophen Tablets as the First Opioid Analgesic 5mg/325mg Initiate treatment with Hydrocodone Bitartrate and Acetaminophen Tablets in a dosing range of 1 to 2 tablets every 4 to 6 hours as needed for pain, at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient’s response to their initial dose of Hydrocodone Bitartrate and Acetaminophen Tablets. The total daily dosage should not exceed 8 tablets. 7.5mg/325mg 10mg/325mg Initiate treatment with Hydrocodone Bitartrate and Acetaminophen Tablets 1 every 4 to 6 hours as needed for pain, at the lowest dose necessary to achieve adequate analgesia. Titrate the dose based upon the individual patient’s response to their initial dose of Hydrocodone Bitartrate and Acetaminophen Tablets. The total daily dosage should not exceed 6 tablets. Conversion from Other Opioids to Hydrocodone Bitartrate and Acetaminophen Tablets There is inter-patient variability in the potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dosage of Hydrocodone Bitartrate and Acetaminophen Tablets. It is safer to underestimate a patient’s 24-hour Hydrocodone Bitartrate and Acetaminophen Tablets dosage than to overestimate the 24-hour Hydrocodone Bitartrate and Acetaminophen Tablets dosage and manage an adverse reaction due to overdose. Conversion from Hydrocodone Bitartrate and Acetaminophen Tablets to Extended-Release Hydrocodone The relative bioavailability of hydrocodone from Hydrocodone Bitartrate and Acetaminophen Tablets 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. Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with Hydrocodone Bitartrate and Acetaminophen Tablets [see WARNINGS, Life-Threatening Respiratory Depression;PRECAUTIONS, Information for Patients and/or Caregivers]. Inform patients and caregivers about the various ways to obtain nal …

Hydrocodone Bitartrate and Acetaminophen Tablet 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]

The following adverse reactions have been identified during post approval use of Hydrocodone Bitartrate and Acetaminophen Tablet. 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 to drug 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, allergic reactions Hematological – Thrombocytopenia, agranulocytosis. Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. •Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. •Anaphylaxis: Anaphylaxis has been reported with ingredients contained in Hydrocodone Bitartrate and Acetaminophen Tablets. •Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids for an extended period of time [see CLINICAL PHARMACOLOGY]. Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see WARNINGS]. Hypoglycemia: Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g., diabetes).

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 4,5α-epoxy-3-methoxy-17-methylmorphinan-6-one tartrate (1:1) hydrate (2:5). It has the following structural formula: [hydroc-struct] 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: [aceto-struct] Each Hydrocodone Bitartrate and Acetaminophen Tablet USP, 5 mg/325 mg contains: Hydrocodone Bitartrate.............................5 mg Acetaminophen.....................................325 mg Each Hydrocodone Bitartrate and Acetaminophen Tablet USP, 7.5 mg/325 mg contains: Hydrocodone Bitartrate.............................7.5 mg Acetaminophen.....................................325 mg Each Hydrocodone Bitartrate and Acetaminophen Tablet USP, 10 mg/325 mg contains: Hydrocodone Bitartrate.............................10 mg Acetaminophen.....................................325 mg In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, FD&C yellow#6 aluminum lake (5 mg/325 mg only), and FD&C blue#1 aluminum lake (10 mg/325 mg only). Meets USP Dissolution Test 2.

Following an acute overdosage, toxicity may result from hydrocodone or acetaminophen. Clinical Presentation Acute overdosage with Hydrocodone Bitartrate and Acetaminophen Tablets can 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, hypoglycemia, partial or complete airway obstruction, atypical snoring, and death. Marked mydriasis rather than miosis may 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 and institution of assisted or controlled ventilation, if needed. Employ other supportive measures (including oxygen and vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life-support techniques. Opioid antagonists, such as naloxone, are specific antidotes to respiratory depression resulting from opioid overdose. For clinically significant respiratory or circulatory depression secondary to Opioid overdose, administer an opioid antagonist. Because the duration of opioid reversal is expected to be less than the duration of action of Hydrocodone Bitartrate and Acetaminophen Tablets in Hydrocodone Bitartrate and Acetaminophen Tablets, carefully monitor the patient until spontaneous respiration is reliably re-established. If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information. In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome. The severity of the withdrawal symptoms experienced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be initiated with care and 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 hours post-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 of intoxication.

Hydrocodone Bitartrate and Acetaminophen Tablets USP are supplied as follows: Strength How Supplied Each tablet contains: Description of tablet Hydrocodone Bitartrate Acetaminophen 5 mg/325 mg Bottles of 20 ................. NDC 0406-0123-20 Bottles of 30 ................. NDC 0406-0123-30 Bottles of 60 ................. NDC 0406-0123-60 Bottles of 90 ................. NDC 0406-0123-90 Bottles of 100 ............... NDC 0406-0123-01 Bottles of 120 ................ NDC 0406-0123-12 Bottles of 500 ............... NDC 0406-0123-05 Bottles of 1000 .............. NDC 0406-0123-10 Unit Dose (10 x 10) ........ NDC 0406-0123-62 5 mg 325 mg It is available as a capsule-shaped white tablet debossed with M365 on one side and bisected on the other side. 7.5 mg/325 mg Bottles of 90 ................. NDC 72189-406-90 Unit Dose (10 x 10) ........ NDC 0406-0124-62 7.5 mg 325 mg It is available as an unscored oval-shaped white tablet debossed with M366 on one side. 10 mg/325 mg Bottles of 20 ................. NDC 0406-0125-20 Bottles of 30 ................. NDC 0406-0125-30 Bottles of 60 ................. NDC 0406-0125-60 Bottles of 90 ................. NDC 0406-0125-90 Bottles of 100 ............... NDC 0406-0125-01 Bottles of 120 ................ NDC 0406-0125-12 Bottles of 500 ............... NDC 0406-0125-05 Bottles of 1000 .............. NDC 0406-0125-10 Unit Dose (10 x 10) ........ NDC 0406-0125-62 10 mg 325 mg It is available as a capsule-shaped white tablet debossed with M367 on one side and bisected on the other side. Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from light. Dispense in a tight, light-resistant container (as defined in USP) with a child-resistant closure. Store hydrocodone bitartrate and acetaminophen tablets securely and dispose of properly (see PRECAUTIONS, INFORMATION FOR PATIENTS). Mallinckrodt, the “M” brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. © 2020 Mallinckrodt. SpecGx LLC Webster Groves, MO 63119 USA Rev 08/2020 MallinckrodtTM Pharmaceuticals An electronic copy of this medication guide can be obtained from www.mallinckrodt.com/Medguide/MG20H32.pdf or by calling 1-800-778-7898 for alternate delivery options.