Hydrocodone Bitartrate and Acetaminophen (hydrocodone bitartrate 7.5 mg acetaminophen 650 mg) Dailymed

Labor And Delivery

As with all narcotics, administration of hydrocodone bitartrate and acetaminophen tablets to the mother shortly before delivery may result in some degree of respiratory depression in the newborn, especially if higher doses are used.

Nursing Mothers

Acetaminophen is excreted in breast milk in small amounts, but the significance of its effects on nursing infants is not known. It is not known whether hydrocodone is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from hydrocodone and acetaminophen, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Clinical studies of hydrocodone bitartrate and acetaminophen tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Hydrocodone and the major metabolites of acetaminophen are known to be substantially excreted by the kidney. Thus the risk of toxic reactions may be greater in patients with impaired renal function due to the accumulation of the parent compound and/or metabolites in the plasma. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Hydrocodone may cause confusion and over-sedation in the elderly; elderly patients generally should be started on low doses of hydrocodone bitartrate and acetaminophen tablets and observed closely.

Adverse Reactions

The most frequently reported adverse reactions are 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 uled in the OVERDOSAGE section.

Drug Abuse And Dependence

Misuse, Abuse, and Diversion of Opioids

Hydrocodone bitartrate and acetaminophen tablets contain hydrocodone, an opioid agonist, and is a Schedule III controlled substance. Hydrocodone bitartrate and acetaminophen, and other opioids, used in analgesia can be abused and are subject to criminal diversion.

Addiction is a primary, chronic, neurobiologic disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease utilizing a multidisciplinary approach, but relapse is common.

“Drug seeking” behavior is very common in addicts and drug abusers. 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 prior medical records or contact information for other treating physician(s). “Doctor shopping” to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Physical dependence usually assumes clinically significant dimensions only after several weeks of continued opioid use, although a mild degree of physical dependence may develop after a few days of opioid therapy. Tolerance, in which increasingly large doses are required in order to produce the same degree of analgesia, is manifested initially by a shortened duration of analgesic effect, and subsequently by decreases in the intensity of analgesia. The rate of development of tolerance varies among patients. Physicians should be aware that abuse of opioids can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. Hydrocodone bitartrate and acetaminophen, like other opioids, may be diverted for non-medical use. Record-keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Overdosage

Following an acute overdosage, toxicity may result from hydrocodone or acetaminophen.

Signs and Symptoms

Hydrocodone: Serious overdose with hydrocodone is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur.

Acetaminophen: In acetaminophen overdosage: dose-dependent, potentially fatal hepatic necrosis is the most serious adverse effect. Renal tubular necrosis, hypoglycemic coma, and thrombocytopenia 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.

In adults, hepatic toxicity has rarely been reported with acute overdoses of less than 10 grams, or fatalities with less than 15 grams

Treatment

A single or multiple overdose with hydrocodone and acetaminophen is a potentially lethal polydrug overdose, and consultation with a regional poison control center is recommended.

Immediate treatment includes support of cardiorespiratory function and measures to reduce drug absorption. Vomiting should be induced mechanically, or with syrup of ipecac, if the patient is alert (adequate pharyngeal and laryngeal reflexes). Oral activated charcoal (1 g/kg) should follow gastric emptying. The first dose should be accompanied by an appropriate cathartic. If repeated doses are used, the cathartic might be included with alternate doses as required. Hypotension is usually hypovolemic and should respond to fluids. Vasopressors and other supportive measures should be employed as indicated. A cuffed endotracheal tube should be inserted before gastric lavage of the unconscious patient and, when necessary, to provide assisted respiration.

Meticulous attention should be given to maintaining adequate pulmonary ventilation. In severe cases of intoxication, peritoneal dialysis, or preferably hemodialysis may be considered. If hypoprothrombinemia occurs due to acetaminophen overdose, vitamin K should be administered intravenously.

Naloxone, a narcotic antagonist, can reverse respiratory depression and coma associated with opioid overdose. Naloxone hydrochloride 0.4 mg to 2 mg is given parenterally. Since the duration of action of hydrocodone may exceed that of the naloxone, the patient should be kept under continuous surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration. A narcotic antagonist should not be administered in the absence of clinically significant respiratory or cardiovascular depression.

If the dose of acetaminophen may have exceeded 140 mg/kg, acetylcysteine should be administered as early as possible. Serum acetaminophen levels should be obtained, since levels four or more hours following ingestion help predict acetaminophen toxicity. Do not await acetaminophen assay results before initiating treatment. Hepatic enzymes should be obtained initially, and repeated at 24-hour intervals.

Methemoglobinemia over 30% should be treated with methylene blue by slow intravenous administration.

The toxic dose for adults for acetaminophen is 10 g

Dosage And Administration

Dosage should be adjusted according to the severity of the pain and response of the patient. However, it should be kept in mind that tolerance to hydrocodone can develop with continued use and that the incidence of untoward effects is dose-related.

The usual adult dosage for Hydrocodone Bitartrate and Acetaminophen Tablets USP is:

7.5 mg/500 mg	The usual adult dosage is one tablet every four to six hours as needed for pain. The total daily dosage should not exceed 6 tablets.
7.5 mg/650 mg	The usual adult dosage is one tablet every four to six hours as needed for pain. The total daily dosage should not exceed 6 tablets.
7.5 mg/750 mg	The usual adult dosage is one tablet every four to six hours as needed for pain. The total daily dosage should not exceed 5 tablets.

How Supplied

Hydrocodone bitartrate and acetaminophen tablets, USP are available in the following strengths:

7.5mg/500mg7.5 mg of hydrocodone bitartrate and 500 mg of acetaminophen. Capsule-shaped, white tablets



bisected on one side and debossed with WATSON 385 on the other side, supplied as follows:

• NDC 12634-783-91 Buler Pack UD 1's
• NDC 12634-783-55 Buler Pack Card of 15x1
• NDC 12634-783-96 Bottle of 6
• NDC 12634-783-00 Bottle of 10
• NDC 12634-783-85 Bottle of 15
• NDC 12634-783-80 Bottle of 20
• NDC 12634-783-71 Bottle of 30
• NDC 12634-783-50 Bottle of 50
• NDC 12634-783-01 Bottle of 100

7.5mg/650mg 7.5 mg of hydrocodone bitartrate and 650 mg of acetaminophen. Capsule-shape, pink tablets bisected on one side and debossed with Watson 502 on the other side, supplied as follows:

7.5mg/750mg 7.5 mg of hydrocodone bitartrate and 750 mg of acetaminophen. Oblong, white tablets bisected on one side and debossed withWatson 387 on the other side, supplied as follows:

• • NDC 12634-166-91 Buler Pack UD 1's
  • NDC 12634-166-61 Buler Pack Card of 10x1
  • NDC 12634-166-00 Bottle of 10
  
  
  
  • • NDC 12634-849-91 Buler Pack UD 1's
    • NDC 12634-849-61 Buler Pack Card of 10x1
    • NDC 12634-849-55 Buler Pack Card of 15x1
    • NDC 12634-849-00 Bottle of 10
    • NDC 12634-849-82 Bottle of 12
    • NDC 12634-849-85 Bottle of 15
    • NDC 12634-849-80 Bottle of 20
    • NDC 12634-849-79 Bottle of 25
    • NDC 12634-849-71 Bottle of 30
    • NDC 12634-849-01 Bottle of 100

Storage

Dispense in a tight, light-resistant container as defined in the USP with a child-resistant closure.

Store at 20 - 25°C (68 - 77°F). (See USP for Controlled Room Temperature).

Package Label

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Package Label.principal Display Panel