HYDROCODONE BITARTRATE AND ACETAMINOPHEN tablet

HYDROCODONE BITARTRATE AND ACETAMINOPHEN by

Drug Labeling and Warnings

HYDROCODONE BITARTRATE AND ACETAMINOPHEN by is a Prescription medication manufactured, distributed, or labeled by EPM Packaging Inc. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

BOXED WARNING

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Hepatotoxicity:
Acetaminophen has been as s ociated with cas es of acute liver failure, at times res ulting in
liver trans plant and death. Mos t of the cas es of liver injury are as s ociated with the us e of
acetaminophen at dos es that exceed 4000 milligrams per day, and often involve more than
one acetaminophen-containing product.

DESCRIPTION

HYDROCODONE BITARTRATE AND ACETAMINOPHEN TABLETS, USP
CII
Rx only

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 nonopiate,
non-salicylate analgesic and antipyretic. It has the following structural formula:
Hydrocodone Bitartrate and Acetaminophen Tablets , USP 5 mg/325 mg
Each tablet contains:
Hydrocodone Bitartrate ................. 5 mg
Acetaminophen ............................. 325 mg
In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, lactose
monohydrate, magnesium stearate, microcrystalline cellulose, povidone, pregelatinized starch, sodium
lauryl sulfate, stearic acid and sugar spheres which are composed of starch derived from corn, FD&C
Red #40, FD&C Yellow #6, and sucrose. Meets USP Dissolution Test 2.
Hydrocodone Bitartrate and Acetaminophen Tablets , USP 7.5 mg/325 mg
Each tablet contains:
Hydrocodone Bitartrate ............. 7.5 mg
Acetaminophen ......................... 325 mg
In addition, each tablet contains the following inactive ingredients: croscarmellose sodium, FD&C Red
#40 aluminum lake, FD&C Yellow #6 aluminum lake, lactose monohydrate, magnesium stearate,
microcrystalline cellulose, povidone, pregelatinized starch, sodium lauryl sulfate, and stearic acid.
Meets USP Dissolution Test 2.
Hydrocodone Bitartrate and Acetaminophen Tablets , USP 10 mg/325 mg
Each tablet contains:
Hydrocodone Bitartrate ............ 10 mg
Acetaminophen ......................... 325 mg
In addition each tablet contains the following inactive ingredients: colloidal silicon dioxide,
croscarmellose sodium, D&C Yellow #10 lake, magnesium stearate, microcrystalline cellulose,
povidone, pregelatinized starch, and stearic acid. May also contain crospovidone. 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-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 & USAGE

Hydrocodone bitartrate and acetaminophen 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

Hepatotoxicity:
Acetaminophen has been as s ociated with cas es of acute liver failure, at times res ulting in liver
trans plant and death. Mos t of the cas es of liver injury are as s ociated with the us e of
acetaminophen at dos es that exceed 4000 milligrams per day, and often involve more than one
acetaminophen-containing product. The exces s ive intake of acetaminophen may be intentional to
caus e s elf-harm or unintentional as patients attempt to obtain more pain relief or unknowingly
take other acetaminophen-containing products .
The ris k of acute liver failure is higher in individuals with underlying liver dis eas e and in
individuals who inges t alcohol while taking acetaminophen.
Ins truct patients to look for acetaminophen or APAP on package labels and not to us e more than
one product that contains acetaminophen. Ins truct patients to s eek medical attention immediately
upon inges tion of more than 4000 milligrams of acetaminophen per day, even if they feel well.
Serious s kin reactions :
Rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematous
pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can
be fatal. Patients should be informed about the signs of serious skin reactions, and use of the drug
should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
Hypers ens itivity/anaphylaxis :
There have been pos t-marketing reports of hypers ens itivity and anaphylaxis as s ociated with us e
of acetaminophen. Clinical s igns included s welling of the face, mouth, and throat, res piratory
dis tres s , urticaria, ras h, pruritus , and vomiting. There were infrequent reports of life-threatening
anaphylaxis requiring emergency medical attention. Ins truct patients to dis continue
Hydrocodone Bitartrate and Acetaminophen Tablets , USP immediately and s eek medical care if
they experience thes e s ymptoms . Do not pres cribe Hydrocodone Bitartrate and Acetaminophen
Tablets , USP for patients with acetaminophen allergy.
Res piratory Depres s ion:
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 Increas ed Intracranial Pres s ure:
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.
Mis us e, Abus e, and Divers ion of Opioids :
Hydrocodone bitartrate and acetaminophen tablets contain hydrocodone, an opioid agonist, and is a
Schedule II 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

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.
Information for Patients /Caregivers :
Do not take Hydrocodone Bitartrate and Acetaminophen Tablets, USP if you are allergic to any of
its ingredients.
If you develop signs of allergy such as a rash or difficulty breathing stop taking Hydrocodone
Bitartrate and Acetaminophen Tablets, USP and contact your healthcare provider immediately.
Do not take more than 4000 milligrams of acetaminophen per day. Call your doctor if you took more
than the recommended dose.
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 Tes ts :
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 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 Tes t Interactions :
Acetaminophen may produce false-positive test results for urinary 5-hydroxyindoleacetic acid.
Carcinogenes is , Mutagenes is , 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 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.
Nurs ing 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 Us e:
Safety and effectiveness in pediatric patients have not been established.

CLINICAL STUDIES

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 Sys tem: Drowsiness, mental clouding, lethargy, impairment of mental and physical
performance, anxiety, fear, dysphoria, psychic dependence, mood changes.
Gas trointes tinal Sys tem: Prolonged administration of hydrocodone bitartrate and acetaminophen tablets
may produce constipation.
Genitourinary Sys tem: Ureteral spasm, spasm of vesical sphincters and urinary retention have been
reported with opiates.
Res piratory Depres s ion: Hydrocodone bitartrate may produce dose-related respiratory depression by
acting directly on the brain stem respiratory centers (see OVERDOSAGE).
Special Sens es : 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
Mis us e, Abus e, and Divers ion of Opioids :
Hydrocodone bitartrate and acetaminophen tablets contain hydrocodone, an opioid agonist, and is a
Schedule II 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

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.

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.
Hydrocodone Bitartrate and Acetaminophen Tablets , USP 5 mg/325 mg
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 12 tablets.
Hydrocodone Bitartrate and Acetaminophen Tablets , USP 7.5 mg/325 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.
Hydrocodone Bitartrate and Acetaminophen Tablets , USP 10 mg/325 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.

HOW SUPPLIED

Hydrocodone Bitartrate and Acetaminophen Tablets , USP 5 mg/325 mg
are supplied as white with orange specks, capsule-shaped, scored tablets, debossed “3604” on one side
and debossed “V” on the reverse side; and supplied as follows:
Bottles of 30: NDC: 0603-3890-16
Bottles of 60: NDC: 0603-3890-20
Bottles of 90: NDC: 0603-3890-02
Bottles of 100: NDC: 0603-3890-21
Bottles of 120: NDC: 0603-3890-22
Bottles of 180: NDC: 0603-3890-04
Bottles of 500: NDC: 0603-3890-28
Bottles of 1000: NDC: 0603-3890-32
Hydrocodone Bitartrate and Acetaminophen Tablets , USP 7.5 mg/325 mg
are supplied as light orange, oval-shaped, scored tablets, debossed “3605” on one side and debossed
“V” on the reverse side; and supplied as follows:
Bottles of 90: NDC: 0603-3891-02
Bottles of 100: NDC: 0603-3891-21
Bottles of 120: NDC: 0603-3891-22
Bottles of 120: NDC: 0603-3891-22
Bottles of 500: NDC: 0603-3891-28
Bottles of 1000: NDC: 0603-3891-32
Hydrocodone Bitartrate and Acetaminophen Tablets , USP 10 mg/325 mg
are supplied as light yellow, modified capsule-shaped, scored tablets, debossed “3601” on one side and
debossed “V” on the reverse side; and supplied as follows:
Bottles of 60: NDC: 0603-3887-20
Bottles of 90: NDC: 0603-3887-02
Bottles of 100: NDC: 0603-3887-21
Bottles of 120: NDC: 0603-3887-22
Bottles of 150: NDC: 0603-3887-26
Bottles of 180: NDC: 0603-3887-04
Bottles of 240: NDC: 0603-3887-12
Bottles of 500: NDC: 0603-3887-28
Bottles of 1000: NDC: 0603-3887-32
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 CII Narcotic.
Manufactured for:
QUALITEST PHARMACEUTICALS
Huntsville, AL 35811
8180185
Rev 8/14

PRINCIPAL DISPLAY PANEL

INGREDIENTS AND APPEARANCE

HYDROCODONE BITARTRATE AND ACETAMINOPHEN 
hydrocodone bitartrate and acetaminophen tablet

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 61502-914(NDC:0603-3891)
Route of Administration	ORAL	DEA Schedule	CII

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
HYDROCODONE BITARTRATE (UNII: NO70W886KK) (HYDROCODONE - UNII:6YKS4Y3WQ7)	HYDROCODONE BITARTRATE	7.5 mg
ACETAMINOPHEN (UNII: 362O9ITL9D) (ACETAMINOPHEN - UNII:362O9ITL9D)	ACETAMINOPHEN	325 mg

Product Characteristics
Color	orange (LIGHT ORANGE)	Score	2 pieces
Shape	OVAL	Size	14mm
Flavor		Imprint Code	3605;V
Contains

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 61502-914-97	500 in 1 BOTTLE; Type 0: Not a Combination Product	01/27/2016
2	NDC: 61502-914-96	100 in 1 BOTTLE; Type 0: Not a Combination Product	01/27/2016
3	NDC: 61502-914-30	30 in 1 BOTTLE; Type 0: Not a Combination Product	01/27/2016
4	NDC: 61502-914-20	20 in 1 BOTTLE; Type 0: Not a Combination Product	01/27/2016
5	NDC: 61502-914-15	15 in 1 BOTTLE; Type 0: Not a Combination Product	01/27/2016
6	NDC: 61502-914-10	10 in 1 BOTTLE; Type 0: Not a Combination Product	01/27/2016
7	NDC: 61502-914-06	6 in 1 BOTTLE; Type 0: Not a Combination Product	01/27/2016

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANDA	ANDA040656	01/27/2016

Labeler - EPM Packaging Inc (079124340)

Registrant - EPM Packaging Inc (079124340)

Establishment
Name	Address	ID/FEI	Business Operations
EPM Packaging Inc		079124340	repack(61502-914)