POLY HIST DHC Liquid

CIII
NDC 50991-521-16
Rx Only

DESCRIPTION:
Each 5 mL (one teaspoonful) for oral administration contains:
Dihydrocodeine Bitartrate*.......................... 7.5 mg
(*WARNING - May be habit forming)
Phenylephrine HCl.................................... 5 mg
Pyrilamine Maleate................................... 7.5 mg

POLY HIST DHC Liquid also contains: Citric Acid, Glycerin, Fruit Gum Flavor, Propylene Glycol,
Sorbitol, Purified Water, Sodium Citrate, Sodium Saccharin.

Dihydrocodeine Bitartrate is an antitussive with the chemical name (Morphinan-6-ol,4,5-epoxy-3-methoxy-17-methyl-,
(5α, 6α)-2,3-dihydroxybutanedioate (1:1) (salt) 4,5α-Epoxy-3-methoxy-17-methylmorphinan-6α-ol (+)-tartrate (salt).
It has the following structural formula:

Phenylephrine hydrochloride is an orally effective nasal decongestant. Chemically it is Benzenemethanol,
3-hydroxy-α-[(methylamino)methyl]-,hydrochloride (R)-, (-)-m-Hydroxy-α- [(methylamino)methyl]benzyl alcohol
hydrochloride. Its chemical structure is as follows:

Pyrilamine Maleate is an antihistamine having the chemical name 1,2-Ethanediamine, N-[(4-methoxyphenyl)methyl]-N',
N'-dimethyl-N-2-pyridinyl-, (Z)-2-butenedioate (1:1) 2-[[2-Dimethylamino)ethyl](p-methoxybenzyl)amino] pyridine
maleate (1:1); Its structural formula is as follows:

CLINICAL PHARMACOLOGY

Dihydrocodeine is a semi-synthetic narcotic analgesic related to codeine, with multiple actions
qualitatively similar to those of codeine; the most prominent of these involve the central nervous
system and organs with smooth muscle components.

Phenylephrine HCl is a sympathomimetic, which acts predominately on alpha-receptors and has little
action on beta-receptors. It therefore functions as an oral nasal decongestant with minimal CNS
stimulation.

Pyrilamine Maleate is an antihistamine used in suppressing symptoms of allergic rhinitis. However, it
is more prone to cause drowsiness than some other antihistamines.

INDICATIONS AND USAGE

POLY HIST DHC Liquid is indicated to control cough and provide for temporary relief from
congestion associated with the upper respiratory tract.

CONTRAINDICATIONS

This combination product is contraindicated in patients with hypersensitivity to dihydrocodeine,
codeine, or any of the active and inactive components listed above, or in any situation where
opioids are contraindicated including significant respiratory depression (in unmonitored settings
or in the absence of resuscitation equipment), acute or severe bronchial asthma or hypercapnia,
and paralytic ileus. Antihistamines and sympathomimetics are contraindicated in patients receiving
antihypertensive or antidepressant drugs containing monoamine oxidase (MAO) inhibitors.
Antihistamines should not be used to treat lower respiratory tract symptoms or be given to
premature or newborn infants. Sympathomimetic agents are contraindicated in patients with
severe hypertension, severe coronary artery disease, patients with narrow angle glaucoma,
bronchial asthma, urinary retention, peptic ulcer, and during an asthma attack. This product is
contraindicated in women who are pregnant.

WARNINGS

General: Considerable caution should be exercised in patients with hypertension, diabetes mellitus,
ischemic heart disease, hyperthyroidism, increased intraocular pressure and prostatic hypertrophy.
The elderly (60 years and older) are more likely to exhibit adverse reactions. Antihistamines may
cause excitability, especially in children. At dosages higher than the recommended dose, nervousness,
dizziness, or sleeplessness may occur.

Usage in Ambulatory Patients: Dihydrocodeine may impair the mental and/or physical abilities
required for the performance of potentially hazardous tasks such as driving a car or operating machinery.

Respiratory Depression: Respiratory depression is the most dangerous acute reaction produced
by opioid agonist preparations, although it is rarely severe with usual doses. Opioids decrease the
respiratory rate, tidal volume, minute ventilation, and sensitivity to carbon dioxide. Respiratory
depression occurs most frequently in elderly more debilitated patients, usually after large initial doses
in non-tolerant patients, or when opioids are given in conjunction with other agents that depress
respiration. This combination product should be used with caution in patients with significant chronic
obstructive pulmonary disease or cor pulmonale and in patients with a substantially decreased
respiratory reserve, hypoxia hypercapnia, or respiratory depression.

Hypotensive Effect: Dihydrocodeine, like all opioid analgesics, may cause hypotension in patients
whose ability to maintain blood pressure has been compromised by a depleted blood volume or who
receive concurrent therapy with drugs such as phenothiazines or other agents which compromise
vasomotor tone. POLY HIST DHC Liquid may produce orthostatic hypotension in ambulatory patients.
This combination product should be administered with caution to patients in circulatory shock, since
vasodilation produced by the drug may further reduce cardiac output and blood pressure.

Dependence: Dihydrocodeine can produce drug dependence of the codeine type and has the
potential of being abused. This product should be prescribed and administered with the appropriate
degree of caution. (See Drug Abuse and Dependence section).

PRECAUTIONS

General: This combination product should be used with caution in elderly or debilitated patients
or those with any of the following conditions: adrenocortical insufficiency (e.g., Addison's disease);
asthma; central nervous system depression or coma; chronic obstructive pulmonary disease;
decreased respiratory reserve (including emphysema, severe obesity, cor pulmonale, or
kyphoscoliosis); delirium tremens; diabetes; head injury; hypotension; hypertension; increased
intracranial pressure; myxedema or hypothyroidism; prostatic hypertrophy or urethral stricture; and
toxic psychosis. The benefits and risks of opioids in patients taking monoamine oxidase inhibitors
and in those with a history of drug abuse should be carefully considered. This combination product
may aggravate convulsions in patients with convulsive disorders, and like all opioids, may induce or
aggravate seizures in some clinical settings.

DRUG INTERACTIONS

General: Sympathomimetics may reduce the antihypertensive effects of methyldopa,
mecamylamine, reserpine and veratrum alkaloids.

Other Central Nervous System Depressants: Patients receiving other opioid analgesics,
sedatives or hypnotics, muscle relaxants, general anesthetics, centrally acting anti-emetics,
phenothiazines or other tranquilizers, or alcohol concomitantly with this combination product
may exhibit additive depressant effects on the central nervous system. When such combined
therapy is contemplated, the dose of one or both agents should be reduced. Concomitant use
of dihydrocodeine and antihistamines with alcohol and other CNS depressants may have an
additive effect.

Monoamine Oxidase Inhibitors: Dihydrocodeine, like all opioids, interact with monoamine
oxidase inhibitors causing central nervous system excitation and hypertension. MAO inhibitors
and beta-adrenergic blockers increase the effects of sympathomimetics. They may also prolong
and intensify the anticholinergic effects of antihistamines.

Information for Patient/Caregivers:

Patients receiving POLY HIST DHC Liquid should be given the following information:
1. Patients should be advised that POLY HIST DHC Liquid may impair the mental or
    physical abilities required for the performance of potentially hazardous tasks such
    as driving a car or operating machinery.
2. Patients should be advised to report adverse experiences occurring during therapy.
3. Patients should be advised not to adjust the dose of POLY HIST DHC Liquid without
    consulting the prescribing professional.
4. Patients should not combine POLY HIST DHC Liquid with alcohol or other central
    nervous system stimulants.
5. Women of childbearing potential who become, or are planning to become pregnant
    should be advised to consult their physician regarding the effects of opioids and other
    drug use during pregnancy on themselves and their unborn child.

Patients should be advised that POLY HIST DHC Liquid is a potential drug of abuse. They
should protect if from theft, and it should never be given to anyone other than the individual
for whom it was prescribed.

Pregnancy: Teratogenic Effects - Pregnancy Category C:

Animal reproduction studies have not been conducted with POLY HIST DHC Liquid. It is also
not known whether this combination product can cause fetal harm when administered to
pregnant women or can affect reproduction capacity in males and females. This combination
product should be given to pregnant women only if clearly needed, especially during the first
trimester.

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. Chlorpromazine 0.7-1.0 mg/kg q6h, phenobarbital 2 mg/kg q6h, and paregoric
24 drops/kg q4h, have been used to treat withdrawal symptoms in infants. The duration of
therapy is 4 to 28 days, with the dosages decreased as tolerated.

Labor and Delivery:

POLY HIST DHC Liquid is not recommended for use by women during and immediately
before labor and delivery because oral opioids may cause respiratory depression in the
newborn.

Pediatric Use:

This product is not recommended for use in children under 6 years of age. Children under two
years may be more susceptible to the respiratory arrest, coma and death. Use of antihistamines
is not recommended in infants. This age group may be at a higher risk than other age groups
because of an increased susceptibility to anticholinergic effects, such as CNS excitation, and an
increased tendency toward convulsions. In older children taking antihistamines, a paradoxical
reaction characterized by hyperexcitability may occur. Very young children may be more sensitive
to the effects, especially the vasopressor effects of sympathomimetic amines.

Geriatric Use:

POLY HIST DHC Liquid should be given with caution to the elderly.

Hepatic Impairment:
POLYHIST DHC Liquid should be given with caution to patients with hepatic insufficiency.
Since, dihydrocodeine is metabolized by the liver; the effects of this combination
product should be monitored closely in such patients.

Renal Impairment:
POLY HIST DHC Liquid should be used with caution and in reduced dosage in the
presence of impaired renal function.

Pancreatic/Biliary Tract Disease:
Opioids may cause spasms of the sphincter of Oddi and should be used with caution in
patients with biliary tract disease including pancreatitis.

ADVERSE REACTIONS

The most frequently observed adverse reactions with dihydrocodeine include light-headedness,
dizziness, drowsiness, headache, fatigue, sedation, sweating, nausea, vomiting, constipation,
pruritis, and skin reactions. With the exception of constipation, tolerance develops to most of
these effects. Other reactions that have been observed with dihydrocodeine or other opioids
include respiratory depression, orthostatic hypotension, cough suppression, confusion, diarrhea,
miosis, abdominal pain, dry mouth, indigestion, anorexia, spasm of biliary tract, and urinary
retention. Physical and psychological dependence are possibilities. Hypersensitivity reactions
(including anaphylactoid reactions), hallucinations, vivid dreams, granulomatous interstitial nephritis,
severe narcosis and acute renal failure have been reported rarely during dihydrocodeine administration.
Other adverse reactions observed with the ingredients in POLY HIST DHC Liquid include, lassitude,
nausea, giddiness, dryness of mouth, blurred vision, cardiac palpitations, flushing, increased irritability
or excitement (especially in children).

DRUG ABUSE AND DEPENDENCE

This combination product is subject to the provisions of the Controlled Substance Act and
has been placed in Schedule III. Dihydrocodeine can produce drug dependence of the codeine
type and therefore has the potential of being abused. Psychological dependence, physical
dependence, and tolerance may develop upon repeated administration of dihydrocodeine, and
it should be prescribed and administered with the same degree of caution appropriate to the
use of other oral opioid medications. Symptoms of dihydrocodeine withdrawal consist of
irritability, restlessness, insomnia, diaphoresis, anxiety and palpitations.

OVERDOSAGE

An overdose of POLY HIST DHC Liquid is a potentially lethal poly-drug overdose situation,
and consultation with a regional Poison Control Center is recommended. A listing of the
poison control centers can be found in standard references such as the Physician's Desk
Reference®.

Signs and Symptoms: Symptoms of overdosage include pinpoint pupils, respiratory depression,
extreme somnolence progressing to stupor, loss of consciousness, or coma, skeletal muscle
flaccidity, cold and clammy skin and other symptoms common with narcotic overdosage.
Convulsions, cardiovascular collapse, and death may occur. A single case of acute
rhabdomyolysis associated with an overdose of dihydrocodeine has been reported.

Recommended Treatment: Immediate treatment of an overdosage of POLY HIST DHC
Liquid includes support of cardiorespiratory function and measures to reduce drug absorption.
Vomiting should be induced with syrup of ipecac, if the patient is alert and has adequate laryngeal
reflexes. Oral activated charcoal should follow. The first dose should be accompanied by an
appropriate cathartic. Gastric lavage may be necessary. Hypotension is usually hypovolemic and
should be treated with fluids. Endotracheal intubation and artificial respiration may be necessary.
The pure opioid antagonist naloxone or nalmefene is a specific antidote against respiratory depression
that results from opioid overdose. Opioid antagonists should not be given in the absence of clinically
significant respiratory or circulatory depression secondary to opioid overdose. They should be
administered cautiously to persons who are known, or suspected to be, physically dependent on any
opioid agonist including dihydrocodeine. In such cases, an abrupt or complete reversal of opioid
effects may precipitate an acute abstinence syndrome. The prescribing information for the specific
opioid antagonist should be consulted for details of their proper use.

DOSAGE AND ADMINISTRATION*

Adults and Children 12 years of age and older:
1 teaspoonful every 4 to 6 hours. Not to exceed 6 teaspoonfuls in a 24 hour period.
Children 6 to 12 years of age:
1/2 teaspoonful every 4 to 6 hours. Not to exceed 3 teaspoonfuls in a 24 hour period.
Not recommended for children under 6 years of age.

*In mild cases or in particularly sensitive patients, less frequent or reduced doses
may be appropriate and adequate.

HOW SUPPLIED

POLY HIST DHC is supplied as an alcohol free, gluten free, sugar free, fruit gum flavor,
clear colored liquid supplied in 16 oz. bottles (NDC 50991-521-16) and 15 mL professional
sample (NDC 50991-521-15).

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.
IN CASE OF ACCIDENTAL OVERDOSE, SEEK PROFESSIONAL ASSISTANCE
OR CONTACT A POISON CONTROL CENTER IMMEDIATELY.

Tamper evident by foil seal under cap. Do not use if foil seal is broken or missing.

Storage:

Store at 20o-25oC (68o-77oF); excursions permitted to 15o-30oC (59o-86oF).
[See USP Controlled Room Temperature.] Protect from freezing.

Dispense in a tight, light-resistant container as defined in the USP/NF with a child-resistant closure.

This bottle not to be dispensed to consumer.

Rx only

Manufactured by:
Great Southern Laboratories
Houston, TX 77099

Distributed for:
Poly Pharmaceuticals
Mobile, AL 36619

Rev. 09/09

PRODUCT PACKAGING:

The packaging below represents the labeling currently used:

Principal Display Panel and Side Panel for 473mL Label:

NDC 50991-521-16

POLY HIST DHC

Antitussive / Decongestant / Antihistamine

Each 5 mL (1 teaspoonful) contains:
Dihydrocodeine Bitartrate*....... 7.5 mg
*(WARNING: May be habit forming)
Phenylephrine HCl....................  5 mg
Pyrilamine Maleate................. 7.5 mg

Fruit Gum Flavor
Alcohol Free / Gluten Free
Sugar Free / Dye Free

CIII
Rx Only

Distributed by:
Poly Pharmaceuticals
Mobile, AL 36619

16 fl oz. (473 mL)

Side Panel:

DOSAGE AND ADMINISTRATION*: Adults and Children 12 years of age and older:
1 teaspoonful every 4 to 6 hours. Not to exceed 6 teaspoonfuls in a 24 hour period.
Children 6 to 12 years of age: 1/2 teaspoonful every 4 to 6 hours. Not to exceed 3
teaspoonfuls in a 24 hour period.
Not recommended for children under 6 years of age.

*In mild cases or in particularly sensitive patients, less frequent or reduced doses may be
appropriate and adequate.

Refer to the attached package insert for full prescribing information.

KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.
IN CASE OF ACCIDENTAL OVERDOSE, SEEK PROFESSIONAL ASSISTANCE
OR CONTACT A POISON CONTROL CENTER IMMEDIATELY.

Tamper evident by foil seal under cap. Do not use if foil seal is broken or missing.

This bottle is not to be dispensed to consumer.

Storage: Store at 20o-25oC (68o-77oF); excursions permitted to 15o-30oC (59o-86oF).
[See USP Controlled Room Temperature.] Protect from freezing.

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

Rx Only

Manufactured by: Great Southern Laboratories, Houston, TX 77099

Distributed for: Poly Pharmaceuticals, Mobile, AL 36619

Iss. 09/09