vicodin
Generic Name: (
hydrocodone bitartrate and acetaminophen)
Dosage Type: tablet Organization: Abbott Laboratories
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: 4,5a-epoxy-3-methoxy-17-methylmorphinan-6-one tartrate (1:1)
hydrate (2:5). It has the following structural formula:
C18H21NO3•C4H6O6•2½H2O M.W.
494.50
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:
C8H9NO2
M.W. 151.16
Each VICODIN tablet contains:
Hydrocodone
Bitartrate 5 mg
Acetaminophen 500 mg
In
addition each tablet contains the following inactive ingredients: colloidal
silicon dioxide, starch, croscarmellose sodium, dibasic calcium phosphate,
magnesium stearate, microcrystalline cellulose, povidone, and stearic acid.
Meets USP Dissolution Test 2.
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 thehalf-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-a- and 6-ß-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.
INDICATIONS AND USAGE
VICODIN tablets are indicated for the relief of moderate
to moderately severe pain.
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.
WARNINGS
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 narcotics
and their capacity to elevate cerebrospinal fluid pressure may be markedly
exaggerated in the presence of head injury, other intracranial lesions or
a preexisting increase in intracranial pressure. Furthermore, narcotics produce
adverse reactions which may obscure the clinical course of patients with head
injuries.
Acute Abdominal Conditions
The administration of narcotics may obscure the
diagnosis or clinical course of patients with acute abdominal conditions.
Misuse, Abuse, and Diversion of Opioids
VICODIN tablets contains hydrocodone an opioid agonist, and
is a Schedule III controlled substance. Opioid agonists have the potential
for being abused and are sought by abusers and people with addiction disorders,
and are subject to diversion.
VICODIN tablets can be
abused in a manner similar to other opioid agonists, legal or illicit. This
should be considered when prescribing or dispensing VICODIN tablets in situations
where the physician or pharmacist is concerned about an increased risk of
misuse, abuse or diversion (see DRUG ABUSE AND DEPENDENCE).
PRECAUTIONS
General
Special Risk Patients
As with any narcotic analgesic agent, VICODIN
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 narcotics, caution should be exercised when VICODIN Tablets are used postoperatively
and in patients with pulmonary disease.
Information for Patients
Hydrocodone, like all narcotics, 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.
Laboratory Tests
In patients with severe hepatic or renal disease,
effects of therapy should be monitored with serial liver and/or renal function
tests.
Drug Interactions
Patients receiving other narcotic analgesics, antihistamines,
antipsychotics, antianxiety agents, or other CNS depressants (including alcohol)
concomitantly with VICODIN 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. VICODIN 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 narcotics, administration of VICODIN
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 the pediatric population
have not been established.
Geriatric Use
Clinical studies of VICODIN (hydrocodone bitartrate
5 mg and acetaminophen 500 mg) 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 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:
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 VICODIN 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
Misuse, Abuse, and Diversion of Opioids
VICODIN contains hydrocodone, an opioid agonist,
and is a Schedule III controlled substance. VICODIN, 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. VICODIN, 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
and 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 endo-tracheal
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 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 dosage should not exceed 8 tablets.
HOW SUPPLIED
VICODIN is supplied as white, capsule-shaped tablets
containing 5 mg hydrocodone bitartrate and 500 mg acetaminophen, bisected
on one side and debossed with "VICODIN" on the other.
Bottles of 100-NDC
0074-1949-14.
Bottles of 500-NDC 0074-1949-54.
Hospital Unit Dose
Package-100 tablets (4 × 25 tablets)-NDC 0074-1949-12.
Storage
Store at 25°C (77°F); excursions permitted
to 15°-30°C (59°-86°F). [See USP Controlled Room Temperature].
Dispense
in a tight, light-resistant container as defined in the USP.
A Schedule
CS-III controlled drug substance.
©Abbott
All rights reserved
Abbott Laboratories
North Chicago,
IL 60064, U.S.A.
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Revised: 03/2007Abbott Laboratories