Hydrocodone bitartrate and acetaminophen
Bryant Ranch Prepack
Bryant Ranch Prepack
Hydrocodone-APAP-10325
FULL PRESCRIBING INFORMATION: CONTENTS*
- HYDROCODONE BITARTRATE AND ACETAMINOPHEN DESCRIPTION
- CLINICAL PHARMACOLOGY
- INDICATIONS & USAGE
- HYDROCODONE BITARTRATE AND ACETAMINOPHEN CONTRAINDICATIONS
- WARNING
- precautions
- HYDROCODONE BITARTRATE AND ACETAMINOPHEN ADVERSE REACTIONS
- Drug abuse and dependence
- OVERDOSAGE
- DOSAGE & ADMINISTRATION
- HOW SUPPLIED
FULL PRESCRIBING INFORMATION
HYDROCODONE BITARTRATE AND ACETAMINOPHEN 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-17-methylmorphinan- 6-one tartrate (1:1) hydrate (2:5).
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.
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,
Ndemethylation and 6-keto reduction to the corresponding 6-a- and
6-b-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.
INDICATIONS & USAGE
Hydrocodone bitartrate and acetaminophen tablets are indicated for the relief of moderate to moderately severe pain.
HYDROCODONE BITARTRATE AND ACETAMINOPHEN CONTRAINDICATIONS
Hydrocodone bitartrate and acetaminophen tablets 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.
WARNING
Respiratory Depression
At high doses or in sensitive patients,
hydrocodone may produce dose-related respiratory depression by acting directly
on the brain stem respiratory center. Hydrocodone also affects the center that
controls respiratory rhythm, and may produce irregular and periodic
breathing.
Head Injury and Increased Intracranial Pressure
The respiratory
depressant effects of opioids and their capacity to elevate cerebrospinal fluid
pressure may be markedly exaggerated in the presence of head injury, other
intracranial lesions or a pre-existing increase in intracranial pressure.
Furthermore, opioids produce adverse reactions which may obscure the clinical
course of patients with head injuries.
Acute Abdominal Conditions
The administration of opioids may obscure the
diagnosis or clinical course of patients with acute abdominal conditions.
precautions
General
Special Risk Patients: As with any opioid analgesic agent,
hydrocodone bitartrate and acetaminophen tablets should be used with caution in
elderly or debilitated patients and those with severe impairment of hepatic or
renal function, hypothyroidism, Addison's disease, prostatic hypertrophy or
urethral stricture. The usual precautions should be observed and the possibility
of respiratory depression should be kept in mind.
Cough Reflex: Hydrocodone suppresses the cough reflex; as with all opioids,
caution should be exercised when hydrocodone bitartrate and acetaminophen
tablets are used postoperatively and in patients with pulmonary
disease.
Information for Patients
Hydrocodone, like all opioids,
may impair the mental and/or physical abilities required for the performance of
potentially hazardous tasks such as driving a car or operating machinery;
patients should be cautioned accordingly.
Alcohol and other CNS depressants may produce an additive CNS depression, when taken with this combination product, and should be avoided.
Hydrocodone may be habit-forming. Patients should take the drug only for as
long as it is prescribed, in the amounts prescribed, and no more frequently than
prescribed.
Drug Interactions
Patients receiving other opioids,
antihistamines, antipsychotics, anti-anxiety 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/Laboratory Test Interactions
Acetaminophen may produce
false-positive test results for urinary 5-hydroxyindoleacetic acid.
Carcinogenesis, Mutagenesis, Impairment of Fertility
No
adequate studies have been conducted in animals to determine whether hydrocodone
or acetaminophen have a potential for carcinogenesis, mutagenesis, or impairment
of fertility.
Pregnancy
Teratogenic Effects: Pregnancy Category C: There
are no adequate and well-controlled studies in pregnant women. Hydrocodone
bitartrate and acetaminophen tablets should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus.
Nonteratogenic Effects: Babies born to mothers who have been taking opioids
regularly prior to delivery will be physically dependent. The withdrawal signs
include irritability and excessive crying, tremors, hyperactive reflexes,
increased respiratory rate, increased stools, sneezing, yawning, vomiting, and
fever. The intensity of the syndrome does not always correlate with the duration
of maternal opioid use or dose. There is no consensus on the best method of
managing withdrawal.
Labor and Delivery
As with all opioids, administration of
this product 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 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 include: light-headedness, dizziness, sedation, nausea and vomiting. These effects seem to be more prominent in ambulatory than in non-ambulatory 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, psychological 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 listed in the OVERDOSAGE section.
Drug abuse and dependence
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.
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.
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 & 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.
The usual adult dosage is one or two tablets every four to six hours as
needed for pain. The total daily dose should not exceed 5 tablets
HOW SUPPLIED
5 mg/325 mg: White to off-white, capsule-shaped, biconvex, uncoated tablets debossed with ‘126’ on one side and scored on the other side. Each tablet contains 5 mg of Hydrocodone Bitartrate, USP and 325 mg of Acetaminophen, USP. They are supplied as follows:
NDC 63629-2947-1 Bottles of 30
NDC 63629-2947-2 Bottles of 90
NDC 63629-2947-3 Bottles of 20
NDC 63629-2947-4 Bottles of 120
NDC 63629-2947-5 Bottles of 100
NDC 63629-2947-6 Bottles of 60
NDC 63629-2947-7 Bottles of 40
NDC 63629-2947-8 Bottles of 84
NDC 63629-2947-9 Bottles of 45
NDC 63629-2947-0 Bottles of 56
Storage: Store at 25°C (77°F); excursions permitted
to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
Dispense in a tight, light-resistant container as defined in the USP.
A Schedule III Controlled Drug Substance.
Distributed By:
Bryant Ranch Prepack
12623 Sherman Way
North Hollywood, CA 91605
Voice (877) 885-0882 Fax (877) 277-7552
MM1
Hydrocodone bitartrate and acetaminophenHydrocodone bitartrate and acetaminophen TABLET
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