Hydrocodone Bitartrate and Ibuprofen

INDICATIONS AND USAGE Hydrocodone bitartrate and ibuprofen tablets are indicated for the short-term management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Carefully consider the potential benefits and risks of hydrocodone bitartrate and ibuprofen tablets and other treatment options before deciding to use hydrocodone bitartrate and ibuprofen tablets. Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals (see WARNINGS: Cardiovascular Thrombotic Events, Gastrointestinal Bleeding, Ulceration, and Perforation ) . Do not use hydrocodone bitartrate and ibuprofen tablets for the treatment of conditions such as osteoarthritis or rheumatoid arthritis. Because of the risks of addiction, abuse, misuse, overdose, and death, which can occur at any dosage or duration and persist over the course of therapy (see WARNINGS ) , reserve opioid analgesics, including hydrocodone bitartrate and ibuprofen tablets, for use in patients for whom alternative treatment options are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.

DOSAGE AND ADMINISTRATION Important Dosage and Administration Instructions Hydrocodone bitartrate and ibuprofen tablets should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals (see WARNINGS ) . Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of hydrocodone bitartrate and ibuprofen tablets for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid 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 ibuprofen tablets. Consider this risk when selecting an initial dose and when making dose adjustments (see WARNINGS ) . Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. The presence of risk factors for overdose should not prevent the management of pain in any patient (see WARNINGS; Addiction, Abuse, and Misuse ; Life-Threatening Respiratory Depression ; Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants ). Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program). There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent. Initial Dosage Use of Hydrocodone Bitartrate and Ibuprofen Tablets as the First Opioid Analgesic Initiate treatment with hydrocodone bitartrate and ibuprofen tablets in a dosing range of one tablet 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 ibuprofen tablets. Dosage should not exceed 5 tablets in a 24-hour period. The lowest effective dose or the longest dosing interval should be sought for each patient (see WARNINGS ) , especially in the elderly. After observing the initial response to therapy with hydrocodone bitartrate and ibuprofen tablets, the dose and frequency of dosing should be adjusted to suit the individual patient's need, without exceeding the total daily dose recommended. Titration and Maintenance of Therapy Individually titrate hydrocodone bitartrate and ibuprofen tablets to a dose that provides adequate analgesia and minimizes adverse reaction…

WARNINGS Hydrocodone Component Addiction, Abuse, and Misuse Hydrocodone bitartrate and ibuprofen contains hydrocodone, a Schedule II controlled substance. As an opioid-containing product, hydrocodone bitartrate and ibuprofen exposes 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 patients appropriately prescribed hydrocodone bitartrate and ibuprofen. Addiction can occur at recommended dosages and if the drug is misused or abused. The risk of opioid-related overdose or overdose-related death is increased with higher opioid doses, and this risk persists over the course of therapy. In postmarketing studies, addiction, abuse, misuse, and fatal and non-fatal opioid overdose were observed in patients with long-term opioid use (see ADVERSE REACTIONS ) . Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing hydrocodone bitartrate and ibuprofen, and reassess all patients receiving hydrocodone bitartrate and ibuprofen for the development of these behaviors and conditions. Risks are increased in patients with a personal or family history of 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 ibuprofen, but use in such patients necessitates intensive counseling about the risks and proper use of hydrocodone bitartrate and ibuprofen along with frequent reevaluation for signs of addiction, abuse, and misuse. Consider recommending or prescribing an opioid overdose reversal agent (see WARNINGS ; DOSAGE AND ADMINISTRATION ) . Opioids are sought for nonmedical use and are subject to diversion from legitimate prescribed use. Consider these risks when prescribing or dispensing hydrocodone bitartrate and ibuprofen. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on careful storage of the drug during the course of treatment and the proper disposal of unused drug (see PRECAUTIONS: Information for Patients ) . 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. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression may include close observation, supportive measures, and use of opioid overdose reversal agents, depending on the patient’s clinical status (see OVERDOSAGE ) . Carbon dioxide (CO 2 ) retention from 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 the use of hydrocodone bitartrate and ibuprofen, the risk is greatest during the initiation of therapy or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of hydrocodone bitartrate and ibuprofen are essential (see DOSAGE AND ADMINISTRATION ) . Overestimating the hydrocodone bitartrate and ibuprofen dosage when converting patients from another opioid product can result in a fatal overdose with the first dose. Accidental ingestion of even one dose of hydrocodone bitartrate and ibuprofen, especially by children, can result in respiratory depression and death due to an overdose of hydrocodone bitartrate and ibuprofen. Educate patients and caregivers on how to recognize respiratory depression and emphasize the importance of calling 911 or getting emergency medical help right awa…

CONTRAINDICATIONS Hydrocodone bitartrate and ibuprofen tablets are contraindicated in patients with: Significant respiratory depression (see WARNINGS: Life-Threatening Respiratory Depression ) . Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment (see WARNINGS: Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients ) . Known or suspected gastrointestinal obstruction, including paralytic ileus (see WARNINGS: Risks of Use in Patients with Gastrointestinal Conditions ) . Known hypersensitivity (e.g., anaphylactic reactions, serious skin reactions) to hydrocodone, ibuprofen, or any components of the drug product (see WARNINGS: Anaphylactic Reactions, Serious Skin Reactions ) . Patients known to be hypersensitive to other opioids may exhibit cross-sensitivity to hydrocodone. History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, sometimes fatal, anaphylactic reactions to NSAIDs have been reported in such patients (see WARNINGS: Anaphylactic Reactions, Exacerbation of Asthma Related to Aspirin Sensitivity ) . In the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS: Cardiovascular Thrombotic Events ) .

ADVERSE REACTIONS The following adverse reactions are described below and elsewhere in the labeling including the WARNINGS section. Addiction, Abuse, and Misuse Life-Threatening Respiratory Depression Neonatal Opioid Withdrawal Syndrome Interactions with Cytochrome P450 3A4 Inhibitors and Inducers Interactions with Benzodiazepines or Other CNS Depressants Adrenal Insufficiency Severe Hypotension Seizures Withdrawal Cardiovascular Thrombotic Events Gastrointestinal Bleeding, Ulceration, and Perforation Hepatotoxicity Hypertension Heart Failure and Edema Renal Toxicity and Hyperkalemia Anaphylactic Reactions Exacerbation of Asthma Related to Aspirin Sensitivity Serious Skin Reactions Premature Closure of Fetal Ductus Arteriosus Hematologic Toxicity Aseptic Meningitis Opioid-Induced Hyperalgesia and Allodynia (see WARNINGS ) Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Hydrocodone bitartrate and ibuprofen was administered to approximately 300 pain patients in a safety study that employed dosages and a duration of treatment sufficient to encompass the recommended usage (see DOSAGE AND ADMINISTRATION ) . Adverse event rates generally increased with increasing daily dose. The event rates reported below are from approximately 150 patients who were in a group that received one tablet of hydrocodone bitartrate and ibuprofen an average of three to four times daily. The overall incidence rates of adverse experiences in the trials were fairly similar for this patient group and those who received the comparison treatment, acetaminophen 600 mg with codeine 60 mg. The following lists adverse events that occurred with an incidence of 1% or greater in clinical trials of hydrocodone bitartrate and ibuprofen, without regard to the causal relationship of the events to the drug. To distinguish different rates of occurrence in clinical studies, the adverse events are listed as follows: name of adverse event = less than 3% adverse events marked with an asterisk * = 3% to 9% adverse event rates over 9% are in parentheses. Body as a Whole Abdominal pain*; Asthenia*; Fever; Flu syndrome; Headache (27%); Infection*; Pain. Cardiovascular Palpitations; Vasodilation. Central Nervous System Anxiety*; Confusion; Dizziness (14%); Hypertonia; Insomnia*; Nervousness*; Paresthesia; Somnolence (22%); Thinking abnormalities. Digestive Anorexia; Constipation (22%); Diarrhea*; Dry mouth*; Dyspepsia (12%); Flatulence*; Gastritis; Melena; Mouth ulcers; Nausea (21%); Thirst; Vomiting*. Metabolic and Nutritional Disorders Edema*. Respiratory Dyspnea; Hiccups; Pharyngitis; Rhinitis. Skin and Appendages Pruritus*; Sweating*. Special Senses Tinnitus. Urogenital Urinary frequency. Incidence less than 1% Body as a Whole Allergic reaction. Cardiovascular Arrhythmia; Hypotension; Tachycardia. Central Nervous System Agitation; Abnormal dreams; Decreased libido; Depression; Euphoria; Mood changes; Neuralgia; Slurred speech; Tremor, Vertigo. Digestive Chalky stool; "Clenching teeth"; Dysphagia; Esophageal spasm; Esophagitis; Gastroenteritis; Glossitis; Liver enzyme elevation. Metabolic and Nutritional Weight decrease. Musculoskeletal Arthralgia; Myalgia. Respiratory Asthma; Bronchitis; Hoarseness; Increased cough; Pulmonary congestion; Pneumonia; Shallow breathing; Sinusitis. Skin and Appendages Rash; Urticaria. Special Senses Altered vision; Bad taste; Dry eyes. Urogenital Cystitis; Glycosuria; Impotence; Urinary incontinence; Urinary retention. Postmarketing Experience The following adverse reactions have been identified during post approval use of hydrocodone. 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 relatio…