ENDAL CD - codeine phosphate, phenylephrine hydrochloride and diphenhydramine hydrochloride syrup 
Tiber Laboratories

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Endal CD Syrup

ENDAL CD SYRUP

Antitussive/Decongestant
Antihistamine
Rx Only

CV

DESCRIPTION
A cherry-flavored, sugar-free, alcohol-free, dye-free, clear syrup for oral administration.

Each 5 mL (teaspoonful) contains:
Codeine phosphate...................... 7.5 mg
(WARNING: May be habit forming)
Phenylephrine hydrochloride......... 7.5 mg
Diphenhydramine hydrochloride..... 10 mg

The phosphate salt of codeine occurs as white, needle-shaped crystals or white crystalline powder. Codeine
phosphate is freely soluble in water and slightly soluble in alcohol. The chemical name is: Morphinan-6-ol,7,
8-didehydroxy-4,5-epoxy-3-methoxy-17-methyl-, (5α, 6α)-,phosphate (1:1) (salt), hemihydrate. Its structure is
as follows:

Codeine Phosphate Chemical Structure


Phenylephrine hydrochloride is a mydriatic and a decongestant and occurs as bitter crystals. The chemical
name is: (-)-m-hydroxy-α-[(methylamino)methyl] benzyl alcohol hydrochloride. Its structure is as follows:

Phenylephrine Hydrochloride Chemical Structure


Diphenhydramine hydrochloride is an antihistaminic. The chemical name is 2-(diphenylmethoxy)-N, N-
dimethylethylamine hydrochloride. Its structure is as follows:

Diphenhydramine Hydrochloride Chemical Structure


Inactive ingredients: Glycerin, Propylene Glycol, Sorbitol, Citric Acid, Sodium Citrate, Sodium Saccharin,
Cherry Flavor, Purified Water.

CLINICAL PHARMACOLOGY

Codeine Phosphate
Codeine is a centrally acting analgesic and antitussive which is well absorbed orally. Following absorption,
codeine is metabolized by the liver and metabolic products are excreted in the urine.

Phenylephrine Hydrochloride
Phenylephrine acts predominantly by a direct action on alpha (α) adrenergic receptors. In therapeutic doses,
the drug has no significant stimulant effect on the beta (β) adrenergic receptors of the heart. Following oral
administration, constriction of blood vessels in the nasal mucosa may relieve nasal congestion. In therapeutic
doses the drug causes little, if any, central nervous system stimulation.

Diphenhydramine Hydrochloride

Diphenhydramine hydrochloride is an ethanolamine antihistamine with anticholinergic (drying) and sedative
effects. It competitively antagonizes histamine at H1, histamine receptors in the central nervous system and
in the periphery. Histaminergic effects (increased capillary permeability and dilatation, edema formation, "flare"
and "itch" response, vasoconstriction and vasodilatation, and gastrointestinal and smooth-muscle constriction)
are especially blocked by diphenhydramine. H1 antihistamines competitively antagonize histamine binding and
do not block its release.

INDICATIONS

ENDAL® CD is indicated for the symptomatic relief of cough, nasal and Eustachian tube congestion and
discomfort associated with the common cold, sinusitis and acute upper respiratory tract infections.

CONTRAINDICATIONS

Hypersensitivity to phenylephrine, codeine, sympathomimetic amines, diphenhydramine, or other
antihistamines of similar chemical structure. Because of its drying effect on lower respiratory secretions,
ENDAL® CD is not recommended in the treatment of bronchial asthma. Also contraindicated in patients
with severe hypertension or severe coronary artery disease, in patients on MAO inhibitor therapy, in
patients with narrow-angle glaucoma, urinary retention, or peptic ulcer, during an asthmatic attack, in
nursing mothers, and in premature or newborn infants.

WARNINGS

Sympathomimetic amines should be used judiciously and sparingly in patients with hypertension, diabetes
melitus, ischemic heart disease, increased intraocular pressure, hyperthyroidism or prostatic hypertrophy.
Sympathomimetics may produce central nervous system stimulation with convulsions or cardiovascular
collapse with accompanying hypotension.

Antihistamines may impair mental and physical abilities required for the performance of potentially hazardous
tasks, such as driving a vehicle or operating machinery.

Diphenhydramine-containing products should not be used in combination with other diphenhydramine formulations;
in rare cases toxic psychosis has occurred in children who received combinations of two or more diphenhydramine
formulations by any route of administration including topically applied preparations.

Respiratory Depression

At high doses or in sensitive patients, codeine may produce dose-related respiratory depression by acting directly
on the brain stem respiratory center. Codeine 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.

Infants and Children

Diphenhydramine should not be administered to premature or full-term neonates. Infants may have greater
susceptibility than adults to the toxic effects of diphenhydramine. Adults who administer diphenhydramine to
children should be aware that children may be at an increased risk for central nervous system stimulation.
Antihistamines may impair mental alertness in children.

PRECAUTIONS

Special Risk Patients
As with any narcotic analgesic agent, ENDAL® CD 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. Use diphenhydramine hydrochloride with precaution in patients with
narrow-angle glaucoma, stenosing peptic ulcer disease, pyloroduodenal obstruction, symptomatic prostatic
hypertrophy, or bladder-neck obstruction, history or bronchial asthma, increased intraocular pressure,
hyperthyroidism, cardiovascular disease, or hypertension. Elderly are more susceptible to the side effects of
diphenhydramine. Concomitant use of CNS depressants, including alcohol, may potentiate the sedative effects
of diphenhydramine.

Information for Patients

ENDAL® CD, like all narcotics and antihistamines, 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. Antihistamines may cause drowsiness and ambulatory patients who operate
machinery and or motor vehicles should be cautioned accordingly.

Cough Reflex
Codeine, suppresses the cough reflex; as with all narcotics, caution should be exercised when ENDAL® CD
is used postoperatively and in patients with pulmonary disease.

Drug Interactions

Patients receiving other narcotic analgesics, antipsychotics, antianxiety agents, or other CNS depressants
(including alcohol) concomitantly with ENDAL® CD 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 codeine preparations may increase the
effect of either the antidepressant or hydrocodone. The concurrent use of anticholinergics with codeine
may produce paralytic ileus.

Concomitant use of antihistamines with alcohol, tricyclic antidepressants, barbiturates and other CNS
depressants may have an additive effect.

MAO inhibitors and beta adrenergic blockers increase the effect of sympathomimetics. Sympathomimetics
may reduce the antihypertensive effects of methyldopa, mecamylamine, reserpine and veratrum alkaloids.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals to determine mutagenic and carcinogenic potential have not been performed.

Usage in Pregnancy

Teratogenic Effects: Pregnancy Category C. Animal reproduction studies have not been conducted with
ENDAL® CD. It is also not known whether ENDAL® CD can cause fetal harm when administered to a
pregnant woman or can affect reproduction capacity. ENDAL® CD should be given to a pregnant woman
only if clearly needed. Codeine has been shown to be teratogenic in hamsters when given in doses 700
times the human dose. There are no adequate and well-controlled studies in pregnant women. ENDAL® CD
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. Chlorpromazine 0.7 to 1 mg/kg q6h, and paregoric
2 to 4 drops/kg 4qh, have been used to treat withdrawal symptoms in infants. The duration of therapy is
4 to 28 days, with the dosage decreased as tolerated.

Labor and Delivery

As with all narcotics, administration of ENDAL® CD 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

It is not known whether this drug 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 ENDAL® CD, 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 children have not been established.

ADVERSE REACTIONS

Antitussives: may include drowsiness, dizziness, nausea or vomiting, constipation, dry mouth, headache,
nervousness or restlessness, feeling of well-being, confusion, urinary disturbances, increased sweating,
skin rash, hives, itching, swelling of face, flushing, weakness, visual disturbances, change in heart rate,
difficulty breathing, loss of appetite, or general feeling of illness or discomfort. Possible allergic reaction to
material if inhaled, ingested, or in contact with skin.

Sympathomimetic Amines: Hyperreactive individuals may display ephedrine-like reactions such as tachycardia,
palpitations, headache, dizziness, or nausea. Sympathomimetics have been associated with certain untoward
reactions including restlessness, tremor, weakness, pallor, respiratory difficulty, dysuria, insomnia,
hallucinations, convulsions, CNS depression, arrhythmias and cardiovascular collapse with hypotension.

Antihistamines: Patients sensitive to antihistamines may experience mild sedation. Possible side effects of
antihistamines are drowsiness, restlessness, dizziness, weakness, dry mouth, anorexia, nausea, vomiting,
headache, nervousness, blurring of vision, polyuria, heartburn, dysuria and very rarely, dermatitis.

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:
The antiemetic phenothiazines are useful in suppressing the nausea and vomiting
which may occur (see above); however, some phenothiazine derivatives seem to be antianalgesic and to
increase the amount of narcotic required to produce pain relief, while other phenothiazines reduce the amount
of narcotic required to produce a given level of analgesia.

Genitourinary System: Ureteral spasm, spasm of vesical sphincters and urinary retention have been reported.

Respiratory Depression:
Codeine may produce dose-related respiratory depression by acting directly on the brain
stem respiratory center. Codeine also affects the center that controls respiratory rhythm, and may produce
irregular and periodic breathing. If significant respiratory depression occurs, it may be antagonized by the use of
naloxone hydrochloride. Apply other supportive measures when indicated.

DRUG ABUSE AND DEPENDENCE

ENDAL® CD is subject to the Federal Controlled Substance Act (Schedule V).

May be habit forming. Codeine can produce drug dependence of the morphine type and, therefore, has
the potential for being abused. Psychic depedence, physical dependence and tolerance may develop upon
repeated administration of ENDAL® CD, and it should be prescribed and administered with the same degree
of caution appropriate to the use of other narcotic drugs.

OVERDOSAGE

Overdose effects of Codeine phosphate may include cold, clammy skin; confusion; convulsions; severe
dizziness; drowsiness; nervousness or restlessness; weakness; low blood pressure; pinpoint pupils;
slow heartbeat; slow or troubled breathing; and unconsciousness.

Treatment: Recommended treatment of opioid analgesic overdose may consist of the following: induced
vomiting or perform gastric lavage (if the opioid was taken orally). Administer naloxone (an opioid
antagonist) as a single dose of between 400 micrograms and 2 mg, preferably by intravenous infusion.
Administer intravenous fluids and/or vasopressors and use other supportive measures as needed.
Continuously monitor patient (mandatory because the duration of action of the opioid may exceed that of
the antagonist) and administer additional naloxone as needed. Alternatively, initial treatment may be
followed by continuous intravenous infusion of naloxone.

Gastric emptying may be useful in removing unabsorbed drug.

Diphenhydramine Hydrochloride

Mild overdose of diphenhydramine leads to sedation. Moderate to severe diphenhydramine overdose
produces predictable anticholinergic effects: agitated delirium, mydriasis, dry mouth, decreased
gastrointestinal motility, urinary retention, and erythema. Rarely, diphenhydramine overdose may cause
rhabdomyolysis. Life-threatening overdose is characterized by hyperthermia (from a combination of
musculoskeletal action in an agitated patient who is unable to lose heat because of an inability to sweat),
seizures, and ventricular tachycardia. Mild to moderate overdoses can be treated supportively. Sedation
for severe agitation can be accomplished by intravenous benzodiazepines or physostigmine. Ventricular
arrhythmia is treated with intravenous sodium bicarbonate or hypertonic saline.

DOSAGE AND ADMINISTRATION

Adults and children 12 years of age and over -
2 teaspoonfuls (10 mL) every 4 hours, not to exceed 8 teaspoonfuls in 24 hours.

Children 6 to under 12 years of age - 1 teaspoonful
(5 mL) every 4 hours, not to exceed 4 teaspoonfuls in 24 hours.

HOW SUPPLIED:

ENDAL® CD is supplied in 16 fl. oz. (473 mL) bottles as a cherry-flavored, sugar-free, alcohol-free,
dye-free, clear syrup, NDC 23589-046-16.

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

Store at 20o to 25oC (68o to 77oF) [See USP Controlled Room Temperature].

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

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

Manufactured for:
TIBER LABORATORIES
Suwanee, GA 30024

U.S. Patent #6,979,689

Manufactured by:
Great Southern Laboratories
Houston, TX 77099

Rev. 11/09

PRODUCT PACKAGING:

The packaging below represents the labeling currently used:

Principal Display Panel and Side Panel:


NDC 23589-046-16

TIBER LABORATORIES

Rx Only

Endal® CD
Syrup

Cough Suppressant / Decongestant / Antihistamine

Cherry Flavor


Each 5 mL (teaspoonful) contains:
Codeine Phosphate................. 7.5 mg
(WARNING: MAY BE HABIT-FORMING)
Phenylephrine HCl.................. 7.5 mg
Diphenhydramine HCl.............. 10 mg

CV

Sugar Free / Alcohol Free / Dye-Free

NET: 1 PINT (473 mL)


DOSAGE AND ADMINISTRATION:
Adults and children 12 years of age and over-
2 teaspoonfuls (10 mL) every 4 hours, not to exceed 8 teaspoonfuls in 24 hours.
Children 6 to under 12 years of age-
1 teaspoonful (5 mL) every 4 hours, not to exceed 4 teaspoonfuls in 24 hours.

Refer to the attached package insert for complete dosing information.

KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN.

IN CASE OF ACCIDENTAL OVERDOSE, SEEK PROFESSIONAL
ASSISTANCE OR CONTACT A POISON CONTROL CENTER IMMEDIATELY.

Store at 20o to 25oC (68o to 77oF) [See USP Controlled Room Temperature]. Dispense in a tight,
light-resistant container as defined in the USP/NF with a child-resistant closure.

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.

Manufactured for:
TIBER LABORATORIES
Suwanee, GA 30024

U.S. Patent #6,979,689

Manufactured by:
Great Southern Laboratories
Houston, TX 77099

Rev. 11/09

Endal CD Packaging

Endal CD Packaging

Endal CD Packaging


ENDAL  CD
codeine phosphate, phenylephrine hydrochloride, and diphenhydramine hydrochloride   syrup
Product Information
Product TypeHUMAN PRESCRIPTION DRUGNDC Product Code (Source)23589-046
Route of AdministrationORALDEA ScheduleCV    
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
Codeine Phosphate (Codeine) Codeine Phosphate7.5 mg  in 5 mL
Phenylephrine Hydrochloride (Phenylephrine) Phenylephrine Hydrochloride7.5 mg  in 5 mL
Diphenhydramine Hydrochloride (Diphenhydramine) Diphenhydramine Hydrochloride10 mg  in 5 mL
Inactive Ingredients
Ingredient NameStrength
No Inactive Ingredients Found
Product Characteristics
Color    Score    
ShapeSize
FlavorCHERRYImprint Code
Contains    
Packaging
#NDCPackage DescriptionMultilevel Packaging
123589-046-16473 mL In 1 BOTTLENone

Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
unapproved drug other12/09/2009

Labeler - Tiber Laboratories (008913939)
Registrant - Great Southern Laboratories (056139553)
Establishment
NameAddressID/FEIOperations
Great Southern Laboratories056139553manufacture
Revised: 12/2009Tiber Laboratories