Overview
11 DESCRIPTION APADAZ (benzhydrocodone and acetaminophen) tablet is an immediate-release, fixed-dose combination of an opioid agonist and acetaminophen. APADAZ tablets are white to off-white, capsule shaped tablets that contain 4.08 mg, 6.12 mg, or 8.16 mg of benzhydrocodone (equivalent to 4.45 mg, 6.67 mg, 8.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Benzhydrocodone Benzhydrocodone is a prodrug of hydrocodone. Hydrocodone Hydrocodone is a 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.
Indications
- 1 INDICATIONS AND USAGE APADAZ is indicated for the short-term (no more than 14 days) management of acute 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 any dosage or duration [see Warnings and Precautions ( 5.1 ) ] reserve APADAZ for use in patients for whom alternative treatment options [e.g.
Common Doses
- 4000 mg
Dosage
2 DOSAGE AND ADMINISTRATION APADAZ should be prescribed only by healthcare professionals who are knowledgeable about the use of opioids and how to mitigate the associated risks. ( 2.1 ) Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of APADAZ 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. ( 2.1 , 5 ) Many acute pain conditions (e.g.
Black Box Warning
WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF APADAZ Addiction, Abuse, and Misuse Because the use of APADAZ exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions ( 5.1 )] . Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of APADAZ, especially during initiation or following a...
Contraindications
- 4 CONTRAINDICATIONS APADAZ is contraindicated in patients with: Significant respiratory depression [see Warnings and Precautions ( 5.3 )] Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions ( 5.8 )] Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions ( 5.14 )] Hypersensitivity to hydrocodone or acetaminophen, or any other component of this product (e.g., anaphylaxis) [see Warnings and Precautions ( 5.
Side Effects
- 6 ADVERSE REACTIONS The following serious adverse reactions are described, or described in greater detail, in other sections: Addiction, Abuse, and Misuse [see Warnings and Precautions ( 5.1 )] Life-Threatening Respiratory Depression [see Warnings and Precautions ( 5.2 )] Interactions with Benzodiazepines and other CNS Depressants [see Warnings and Precautions ( 5.3 )] Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions ( 5.4 )] Hepatotoxicity [see Warnings and Precautions ( 5.7 )] Opioid-Induced Hyperalgesia and Allodynia [see Warnings and Precautions ( 5.
Interactions
- 7 DRUG INTERACTIONS Table 2. Clinically Significant Drug Interactions with APADAZ. CYP3A4 and 2D6 Inhibitors Clinical Impact: The concomitant use of APADAZ and CYP3A4 inhibitors can increase the plasma concentration of hydrocodone, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of APADAZ and CYP2D6 and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of APADAZ is achieved [see Warnings and Precautions ( 5.5 )] .