Hydrocodone Bitartrate & Acetaminophen

/Hydrocodone Bitartrate & Acetaminophen
Hydrocodone Bitartrate & Acetaminophen2018-09-06T09:12:40+00:00

Prescription Drug Name:

Hydrocodone Bitartrate & Acetaminophen

ID:

a6765670-7036-4d4b-9349-94969b6841d4

Code:

34391-3

DESCRIPTION


id: df27ca3a-55fc-4eb0-86f2-d3ab70f0776a
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

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). 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
10 mg/325 mgEach tablet contains:     Hydrocodone Bitartrate ………… 10 mg
    Acetaminophen
……………………. 325 mg
In addition each tablet contains the following inactive ingredients:
colloidal silicon dioxide, croscarmellose sodium, D and C Yellow No. 10 lake,
magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch,
and stearic acid. May also contain crospovidone. Meets USP Dissolution Test 1.

CLINICAL PHARMACOLOGY


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displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

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:


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displayName: PHARMACOKINETICS SECTION
FDA Article Code: 43682-4

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-ketoreduction to the
corresponding 6-α- and 6-β-hydroxymetabolites. 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


id: 5402d723-aabf-499c-a4a1-6cc6ef337dbf
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

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

CONTRAINDICATIONS


id: 764c1976-780a-46a1-829f-876ad40726a3
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

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


id: 159fd1a8-77aa-42f8-8ddb-93ecec9066b9
displayName: WARNINGS SECTION
FDA Article Code: 34071-1

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:Hydrocodone bitartrate and acetaminophen tablets contain
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.
Hydrocodone bitartrate and acetaminophen tablets can be abused in a manner
similar to other opioid agonists, legal or illicit. This should be considered
when prescribing or dispensing hydrocodone bitartrate and acetaminophen 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


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displayName: WARNINGS AND PRECAUTIONS SECTION
FDA Article Code: 43685-7

General:
Special
Risk Patients:

As with any narcotic 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 narcotics,
caution should be exercised when hydrocodone bitartrate and acetaminophen
tablets are used postoperatively and in patients with pulmonary disease.
Hydrocodone Bitartrate and Acetaminophen Tablets 7.5 mg/500 mg contain
FD and C Yellow No. 5 (tartrazine) which may cause allergic-type reactions
(including bronchial asthma) in certain susceptible persons. Although the
overall incidence of FD and C Yellow No. 5 (tartrazine) sensitivity in the
general population is low, it is frequently seen in patients who also have
aspirin hypersensitivity.

Information for Patients:


id: c6d4d535-417f-473e-8e2c-009e5a73fb9a
displayName: INFORMATION FOR PATIENTS SECTION
FDA Article Code: 34076-0

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:


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displayName: LABORATORY TESTS SECTION
FDA Article Code: 34075-2

In patients with severe hepatic or renal disease, effects of therapy should be
monitored with serial liver and/or renal function tests.

Drug Interactions:


id: 4b1b9d3e-93bb-4b07-a902-187d09f02405
displayName: DRUG INTERACTIONS SECTION
FDA Article Code: 34073-7

Acetaminophen may produce false-positive test results for urinary
5-hydroxyindoleacetic acid.

Carcinogenesis, Mutagenesis, Impairment of Fertility:


id: a2cc053f-0549-430e-a454-e0c10bef289a
displayName: CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION
FDA Article Code: 34083-6

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:


id: 9af466b5-7f14-49d3-a1cf-b9a74839a6f5
displayName: PREGNANCY SECTION
FDA Article Code: 42228-7


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:


id: ada11a94-c023-4bb2-a0ea-7ae9cfa0b0d3
displayName: LABOR & DELIVERY SECTION
FDA Article Code: 34079-4

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:


id: 39e48491-2b09-44b2-ad83-a3f7f4adc07d
displayName: NURSING MOTHERS SECTION
FDA Article Code: 34080-2

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:


id: 4ec2d6ac-2088-4a88-87d2-20ab9a52d035
displayName: PEDIATRIC USE SECTION
FDA Article Code: 34081-0

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use:


id: 285e4b5b-91b9-4a29-b439-27dc4c7c4e98
displayName: GERIATRIC USE SECTION
FDA Article Code: 34082-8

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


id: 4b0fdbfd-7f04-4fd7-983a-423c0f451bf4
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

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 centers (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


id: e40c48e9-90f0-445b-9d19-e479d16eb267
displayName: DRUG ABUSE AND DEPENDENCE SECTION
FDA Article Code: 42227-9

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 tablets, 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 tablets,
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


id: e7d964db-649e-422c-8acd-6c6f65f46ecd
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

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


id: eeb68a67-12d5-49fd-aa02-9dce27a5c27e
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

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.
Hydrocodone Bitartrate and Acetaminophen Tablets, USP
10 mg/325 mgThe usual adult dosage is one tablet every four to six hours as
needed for pain. The total daily dosage should not exceed 6 tablets.

HOW SUPPLIED


id: 68ed389d-0346-4474-b9f7-18dd20af995a
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Hydrocodone Bitartrate and Acetaminophen Tablets, USP
10 mg/325 mgare supplied as light yellow, modified capsule-shaped, scored
tablets, debossed “3601” on one side and debossed “V” on the reverse side. The
tablets are supplied in containers of 10, 20, and 30.
Storage:Store at 20°-25°C (68°-77°F) [see USP Controlled Room
Temperature].
Dispense in a tight, light-resistant container as defined in the USP/NF with
a child-resistant closure.
A Schedule CIII Narcotic.