Professional Information — Hydrocodone Bitartrate And Acetaminophen 3591 V

Indications and Usage

Hydrocodone and acetaminophen tablets are indicated for the relief of moderate to moderately severe pain.

Dosage and Administration

Dosage should be adjusted according to the severity of the pain and the 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.

Contraindications

This product should not be administered to patients who have previously exhibited hypersensitivity to hydrocodone or acetaminophen.Patients known to be hypersensitive to other opioids may exhibit cross-sensitivity to hydrocodone.

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, and 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 listed in the OVERDOSAGE  section.

Drug Interactions

Patients receiving narcotics, antihistamines, antipsychotics, antianxiety agents, or other CNS depressants (including alcohol) concomitantly with hydrocodone bitartrate and acetaminophen tablets may exhibit an additive CNS depression. When combined therapy is contemplated, the dose of one or both agents should be reduced.

The use of MAO inhibitors or tricyclic antidepressants with hydrocodone preparations may increase the effect of either the antidepressant or hydrocodone.

Drug Abuse and Dependence

Controlled Substance: Hydrocodone Bitartrate and Acetaminophen Tablets are classified as a Schedule III controlled substance.

Abuse and Dependence: Psychic dependence, physical dependence, and tolerance may develop upon repeated administration of narcotics; therefore, this product should be prescribed and administered with caution. However, psychic dependence is unlikely to develop when hydrocodone bitartrate and acetaminophen tablets are used for a short time for the treatment of pain.

Physical dependence, the condition in which continued administration of the drug is required to prevent the appearance of a withdrawal syndrome, assumes clinically significant proportions only after several weeks of continued narcotic use, although some mild degree of physical dependence may develop after a few days of narcotic 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.

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 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: A single or multiple drug 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. Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. Assisted or controlled ventilation should also be considered.

For hydrocodone overdose, primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. The narcotic antagonist naloxone hydrochloride is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to narcotics, including hydrocodone. Since the duration of action of hydrocodone may exceed that of the antagonist, the patient should be kept under continued 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.

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.

Description

Hydrocodone bitartrate and acetaminophen is supplied in tablet form for oral administration.Hydrocodone bitartrate is an opioid analgesic and antitussive 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-17methylmorphinan-6-one tartrate (1:1) hydrate (2:5). It has the following structural formula:

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:

Hydrocodone Bitartrate and Acetaminophen Tablets USP for oral administration are available in a variety of strengths as described in the following table.

In addition, each tablet contains the following inactive ingredients: anhydrous lactose, croscarmellose sodium, crospovidone, magnesium stearate, microcrystalline cellulose, povidone, starch and stearic acid; except the 7.5 mg/325 mg, 10 mg/325 mg and 10 mg/500 mg tablets do not contain anhydrous lactose. The 7.5 mg/325 mg tablets include FD&C Yellow #6 Aluminum Lake; the 7.5 mg/650 mg tablets include FD&C Red #40 Aluminum Lake; the 10 mg/325 mg and 10 mg/750 mg tablets include D&C Yellow #10 Aluminum Lake; the 10 mg/500 mg tablets include FD&C Blue #2 Aluminum Lake; and the 10 mg/650 mg tablets include FD&C Blue #1 Aluminum Lake and D&C Yellow #10 Aluminum Lake. Meets USP Dissolution Test 1.

Clinical Pharmacology

Hydrocodone is a semisynthetic narcotic analgesic and antitussive with multiple actions qualitatively similar to those of codeine. Most of these involve the central nervous system and smooth muscle. The precise mechanism of action of hydrocodone and other opiates is not known, although it is believed to relate to the existence of opiate receptors in the central nervous system. In addition to analgesia, narcotics may produce drowsiness, changes in mood and mental clouding.

The analgesic action of acetaminophen involves peripheral influences, but the specific mechanism is as yet undetermined. Antipyretic activity is mediated through hypothalamic heat regulating centers. Acetaminophen inhibits prostaglandin synthetase. Therapeutic doses of acetaminophen have negligible effects on the cardiovascular or respiratory systems; however, toxic doses may cause circulatory failure and rapid, shallow breathing.

Pharmacokinetics:

The behavior of the individual components is described below.

Hydrocodone: Following a 10 mg oral dose of hydrocodone administered to five adult male subjects, the mean peak concentration was 23.6 ± 5.2 ng/mL. Maximum serum levels were achieved at 1.3 ± 0.3 hours and the half-life was determined to be 3.8 ± 0.3 hours. Hydrocodone exhibits a complex pattern of metabolism including O-demethylation, N-demethylation and 6-keto reduction to the corresponding 6-α- and 6-β- hydroxy-metabolites. See OVERDOSAGE for toxicity information.

Acetaminophen: Acetaminophen is rapidly absorbed from the gastrointestinal tract and is distributed throughout most body tissues. The plasma half-life is 1.25 to 3 hours, but may be increased by liver damage and following overdosage. Elimination of acetaminophen is principally by liver metabolism (conjugation) and subsequent renal excretion of metabolites.

Approximately 85% of an oral dose appears in the urine within 24 hours of administration, most as the glucuronide conjugate, with small amounts of other conjugates and unchanged drug. See OVERDOSAGE for toxicity information.

How Supplied / Storage and Handling

Hydrocodone Bitartrate and Acetaminophen Tablets USP are available in the following strengths:

2.5 mg/500 mg
 2.5 mg hydrocodone bitartrate and 500 mg acetaminophen, oblong, white tablets bisected on one side and debossed with WATSON 388 on the other side, supplied in:
    Bottles of 30      NDC    16590-112-30
    Bottles of 60      NDC    16590-112-60
    Bottles of 90      NDC    16590-112-90
    Bottles of 120    NDC    16590-112-72

7.5 mg hydrocodone bitartrate and 325 mg acetaminophen, capsule shaped, light orange tablets bisected on one side and debossed with

on the other side, supplied in:

Bottles of 15 NDC 16590-114-15

Bottles of 20 NDC 16590-114-20

Bottles of 28 NDC 16590-114-28

Bottles of 30 NDC 16590-114-30

Bottles of 40 NDC 16590-114-40

Bottles of 45 NDC 16590-114-45

Bottles of 60 NDC 16590-114-60

Bottles of 90 NDC 16590-114-90

Bottles of 100 NDC 16590-114-71

Bottles of 120 NDC 16590-114-72

Bottles of 180 NDC 16590-114-82

7.5 mg/500 mg

7.5 mg hydrocodone bitartrate and 500 mg acetaminophen, capsule-shaped, white tablets bisected on one side and debossed with

on the other side, supplied in:

Bottles of 28 NDC 16590-115-28

Bottles of 30 NDC 16590-115-30

Bottles of 45 NDC 16590-115-45

Bottles of 56 NDC 16590-115-56

Bottles of 60 NDC 16590-115-60

Bottles of 90 NDC 16590-115-90

Bottles of 100 NDC 16590-115-71

7.5 mg/650 mg

7.5 mg hydrocodone bitartrate and 650 mg acetaminophen, capsule-shaped, pink tablets bisected on one side and debossed with

on the other side, supplied in:

Bottles of 20 NDC 16590-116-20

Bottles of 30 NDC 16590-116-30

Bottles of 40 NDC 16590-116-40

Bottles of 60 NDC 16590-116-60

Bottles of 90 NDC 16590-116-90

Bottles of 120 NDC 16590-116-72

7.5 mg/750 mg

7.5 mg hydrocodone bitartrate and 750 mg acetaminophen, oblong, white tablets bisected on one side and debossed with

on the other side, supplied in:

Bottles of 10 NDC 16590-117-10

Bottles of 15 NDC 16590-117-15

Bottles of 30 NDC 16590-117-30

Bottles of 40 NDC 16590-117-40

Bottles of 60 NDC 16590-117-60

Bottles of 90 NDC 16590-117-90

Bottles of 120 NDC 16590-117-72

10 mg/325 mg

10 mg hydrocodone bitartrate and 325 mg acetaminophen, capsule-shaped, yellow tablets bisected on one side and debossed with

on the other side, supplied in:

Bottles of 30 NDC 16590-118-30

Bottles of 56 NDC 16590-118-56

Bottles of 60 NDC 16590-118-60

Bottles of 90 NDC 16590-118-90

Bottles of 120 NDC 16590-118-72

Bottles of 150 NDC 16590-118-83

10 mg/500 mg

10 mg hydrocodone bitartrate and 500 mg acetaminophen, capsule-shaped, blue tablets bisected on one side and debossed with

on the other side, supplied in:

Bottles of 30 NDC 16590-119-30

Bottles of 45 NDC 16590-119-45

Bottles of 56 NDC 16590-119-56

Bottles of 60 NDC 16590-119-60

Bottles of 90 NDC 16590-119-90

Bottles of 100 NDC 16590-119-71

Bottles of 150 BDC 16590-119-83

10 mg/650 mg

10 mg hydrocodone bitartrate and 650 mg acetaminophen, oblong, white tablets bisected on one side and debossed with

on the other side, supplied in:

Bottles of 30 NDC 16590-120-30

Bottles of 50 NDC 16590-120-50

Bottles of 60 NDC 16590-120-60

Bottles of 90 NDC 16590-120-90

Bottles of 100 NDC 16590-120-71

Bottles of 180 NDC 16590-120-82

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

Dispense in a tight, light-resistant container with a child-resistant closure.

Manufactured by:

Watson Laboratories, Inc.
Corona, CA 92880 USA

Distributed by:

Watson Pharma, Inc.

Corona, CA 92880 USA                                     Revised: June 2011
                                                                          173191-1

Relabeling and Repackaging by:
STAT Rx USA LLC
Gainesville, GA  30501