Benzhydrocodone and Acetaminophen

Benzhydrocodone and acetaminophen is a combination opioid analgesic approved for short-term use in adults with acute pain.

• Apadaz (oral tablet): Indicated for the short-term management (no more than 14 days) of acute pain severe enough to require an opioid analgesic and for which non-opioid alternatives are inadequate or not tolerated
• Apadaz is not a first-line pain reliever — it is reserved for situations where non-opioid options (such as NSAIDs or other analgesics) have failed or cannot be used
• Apadaz should not be continued long-term unless pain remains severe and alternatives remain inadequate

Benzhydrocodone is a prodrug — after you swallow an Apadaz tablet, enzymes in the intestinal tract convert benzhydrocodone into hydrocodone, the active opioid. Hydrocodone binds to mu-opioid receptors in the brain and spinal cord, which are the body's natural pain-modulating sites. This binding reduces the perception of pain. Acetaminophen works through a separate, not fully understood mechanism — likely acting in the central nervous system — to provide additional pain relief on top of the opioid component.

Apadaz tablets are taken by mouth every 4 to 6 hours as needed for pain. They may be taken with or without food — a high-fat meal slightly slows the rate of hydrocodone absorption but does not change the total amount absorbed. Your prescriber will start you at the lowest number of tablets that controls your pain and adjust from there.

• Do not exceed 12 tablets in a 24-hour period
• Do not exceed the total daily acetaminophen limit across all products you take
• Do not stop abruptly if you have been using it regularly — your doctor will guide you on gradually reducing the dose to avoid withdrawal
• Apadaz is approved for short-term use only — no more than 14 days

The most common side effects reported in clinical trials of Apadaz include:

Less common but reported effects include abdominal pain, bloating, weakness, low blood pressure, and shortness of breath. Seek immediate medical attention for signs of breathing problems, severe allergic reaction, or skin rash — these require urgent care and stopping the medication.

• Breathing problems (respiratory depression): Apadaz can slow or stop breathing, especially when first started or after a dose increase. This risk is highest in elderly, frail, or debilitated patients and those with lung conditions.
• Addiction and misuse: Apadaz is a Schedule II controlled substance. Addiction can occur even at prescribed doses. Patients with a personal or family history of substance use disorder are at higher risk.
• Children and accidental ingestion: Even one tablet can be fatal to a child. Store Apadaz securely and out of reach of all children.
• Liver damage from acetaminophen: Exceeding the safe daily acetaminophen limit — including from other products — can cause acute liver failure, which can be fatal. Check all medications for acetaminophen or "APAP."
• Opioid-induced hyperalgesia: In rare cases, opioids can paradoxically increase pain sensitivity. If your pain worsens after a dose increase, tell your doctor.
• Hormonal effects: Long-term opioid use can affect hormone levels, potentially causing reduced libido, erectile dysfunction, or irregular periods.
• Serotonin syndrome: When used with certain antidepressants or other serotonergic drugs, there is a risk of serotonin syndrome — a potentially life-threatening condition with symptoms like agitation, rapid heart rate, and high temperature.

Apadaz interacts with several common medications and substances — always share your full medication list with your prescriber and pharmacist.

• Benzodiazepines and sedatives (e.g., diazepam, lorazepam, sleep aids): combined use raises the risk of profound sedation, coma, and fatal respiratory depression
• Alcohol: dramatically increases sedation and breathing risk — avoid completely while taking Apadaz
• MAO inhibitors (e.g., phenelzine, tranylcypromine, linezolid): can cause life-threatening reactions; do not use Apadaz within 14 days of an MAOI
• CYP3A4 inhibitors (e.g., erythromycin, ketoconazole, ritonavir): can raise hydrocodone blood levels dangerously high, increasing overdose risk
• CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin): can lower hydrocodone levels, reducing pain control or triggering withdrawal
• Serotonergic drugs (SSRIs, SNRIs, tricyclic antidepressants, triptans, tramadol): risk of serotonin syndrome
• Muscle relaxants (e.g., cyclobenzaprine, metaxalone): can increase respiratory depression when combined with Apadaz
• Other acetaminophen-containing products: stacking acetaminophen sources can push total intake to dangerous levels for the liver
• Diuretics: opioids may reduce their effectiveness by causing the body to retain water
• Anticholinergic drugs: may worsen constipation and increase the risk of urinary retention when used with Apadaz

Not a complete list. The label covers the interactions the manufacturer studied or reported, and our own interaction database does not cover every medicine either. Bring your full medication list, including vitamins and herbal products, to your pharmacist.

• Do not take Apadaz if you have significant respiratory depression (severely slowed breathing)
• Do not take Apadaz if you have acute or severe asthma in an unmonitored setting
• Do not take Apadaz if you have a known or suspected bowel blockage (gastrointestinal obstruction or paralytic ileus)
• Do not take Apadaz if you are allergic to hydrocodone, acetaminophen, or any ingredient in the product
• Tell your doctor if you have a history of substance use disorder, addiction, or mental health conditions — you can still receive appropriate pain treatment, but closer monitoring is needed
• Tell your doctor if you have liver disease or regularly drink alcohol — the acetaminophen in Apadaz can be dangerous
• Tell your doctor if you are pregnant — long-term use can cause neonatal opioid withdrawal syndrome in the newborn, which can be life-threatening
• If breastfeeding, be aware that hydrocodone passes into breast milk; monitor your infant for unusual sleepiness or breathing changes
• Apadaz is not approved for use in patients under 18 years of age
• Older adults (65+) are more sensitive to opioid effects; dosing should start low and be adjusted carefully
• Use with caution if you have kidney or liver impairment — these organs process both hydrocodone and acetaminophen, and impairment can increase drug levels and side effects

An overdose of Apadaz is a medical emergency. Hydrocodone overdose can cause dangerously slowed or stopped breathing, extreme drowsiness progressing to unconsciousness, limpness, pinpoint pupils, cold clammy skin, and possibly death. Acetaminophen overdose can cause severe liver damage — early signs include nausea, vomiting, sweating, and general illness, but liver injury may not become apparent for 48 to 72 hours. If an overdose is suspected, call 911 immediately, administer naloxone if available, and seek emergency care — contact a regional poison control center as well for guidance on both components.

Hydrocodone — the active opioid produced from benzhydrocodone — acts directly on brainstem respiratory centers, which is why it can slow breathing. It also slows movement through the gastrointestinal tract, leading to constipation, and can cause blood vessels to widen (peripheral vasodilation), which may lower blood pressure. Hydrocodone affects the endocrine system over time, potentially reducing the production of hormones like cortisol and testosterone with extended use. The analgesic effect has no ceiling — pain relief increases with dose — but so do side effects including sedation and respiratory depression.

After an Apadaz tablet is swallowed, benzhydrocodone is rapidly converted to hydrocodone by enzymes in the intestinal tract — benzhydrocodone itself is not detectable in the bloodstream. Hydrocodone reaches peak blood levels in about 1 to 2.5 hours (slightly later with a high-fat meal) and has a half-life of approximately 4 to 4.5 hours; steady-state levels are reached within 24 to 36 hours of regular dosing. Hydrocodone is metabolized in the liver — partly through the CYP3A4 and CYP2D6 enzyme pathways — and is primarily eliminated by the kidneys. Acetaminophen is metabolized primarily in the liver and also cleared through the kidneys; its half-life is approximately 4.8 to 5.6 hours.

Store at 20°C to 25°C (68°F to 77°F). Store APADAZ securely and dispose of properly.