Antitussive/Antihistamine/Decongestant
Rx Only
CIII

DESCRIPTION
Each teaspoonful (5 mL) for oral administration contains:
Dihydrocodeine Bitartrate.....................................................7.5 mg
(WARNING-May be habit forming)
Chlorpheniramine Maleate.......................................................2 mg
Pseudoephedrine Hydrochloride.............................................15 mg

This product contains the following inactive ingredients:
Citric Acid, Glycerin, Grape Flavor, Propylene Glycol, Purified Water, Sodium Citrate, Sodium Saccharin, Sorbitol.

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





Chlorpheniramine Maleate is an antihistamine having the chemical name 2-Pyridinepropanamine,γ-(4-chlorophenyl)-N,N-dimethyl-,(Z)-2-butenedioate (1:1).  It has the following chemical structure:




Pseudoephedrine Hydrochloride is a decongestant having the chemical name, Benzenemethanol, α-[1-(methylamino) ethyl]-,[S-(R*R*)-, hydrochloride. It has the following structural formula:

CLINICAL PHARMACOLOGY

Dihydrocodeine is a semisynthetic narcotic analgesic antitussive 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.

Chlorpheniramine is an alkylamine type antihistamine.  This group of antihistamines is among the most active histamine antagonists and is generally effective in relatively low doses.  The drugs are not so prone to produce drowsiness and are therefore among the most suitable agents for daytime use, but a significant proportion of patients do experience this effect.

Pseudoephedrine Hydrochloride is a sympathomimetic amine, 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.

INDICATIONS AND USAGE

This product is indicated for the temporary relief of cough and nasal congestion associated with upper respiratory tract infections and allergies.

CONTRAINDICATIONS

This combination product is contraindicated in patients with hypersensitivity to dihydrocodeine, codeine, or any of the active or 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 sever bronchial asthma or hypercapnia, and paralytic ileus.  Antihistamines are contraindicated in patients receiving antihypertensive or antidepressant drugs containing monoamine oxidase inhibitors (MAOI) since these agents may prolong and intensify the anticholinergic and CNS depressant effects of antihistamines (see Drug Interactions).

Antihistamines should not be used to treat lower respiratory tract symptoms or be given to 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 asthmatic 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 intracular 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 doses 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 opiod agonist preparations, although it is rarely severe with usual doses.  Opioids decrease the respiratory tidal volume, minute ventilation, and sensitivity to carbon dioxide.  Respiratory depression occurs most frequently in elderly or 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.

Hypertensive 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 received concurrent therapy with drugs such as phenothiazine or other agents which compromise vasomotor tone.  This product may produce orthostatic hypotension in ambulatory patients.  This combination product should be administered with caution to patients with 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, sever 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 opiods in patients taking monoamine oxidase inhibitors and i 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

Sympathomimetic amines may reduce the antihypertensive effects of methyldopa, mecamylamine, reserpine, and veratrum alkaloids.

Other CNS 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 product may exhibit additive depressant effects on the central nervous system.  When such combination 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.

ADVERSE REACTIONS

The most frequently observed adverse reaction with dihydrocodeine include lightheadedness, dizziness, drowsiness, headache, fatigue, sedation, sweating, nausea, vomiting, constipation, pruritus, and skin reactions.  With the exception of constipation, tolerance develops to most of these effects.  Other reactions that have been observed with dihydrocodeine or 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 (include anaphylactoid reactions), hallucinations, vivid dreams, granulomatous interstitial nephritis, sever narcosis and acute renal failure have been reported rarely during dihydrocodeine administration.

Other reactions observed with the ingredients in this product 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 Substances 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 repeat administration of dihydrocodeine, and it should be prescribed and administered with the same degree of caution appropriate to the use of other opioid medications.  Symptoms of dihydrocodeine withdrawal consist of irritability, restlessness, insomnia, diaphoresis, anxiety, and palpitations.

OVERDOSAGE

An overdose of this product is a potentially lethal overdose situation, and consultation with a regional Poison Control Center is recommended.  A listing of the Poison Control Center can be found in a standard reference such as the Physician's Desk Reference.

Signs and Symptoms:  Symptoms of an overdose 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 overdose of this product includes support of cardiovascular function and measures to reduce further 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 nalmexone is a specific antidote against respiratory depression that results from opioid overdose.  Opioid antagonists should 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 opiod effects may precipitate an acute abstinence syndrome.  The prescribing information for the specific opioid antagonist should be consulted for details of there proper use.

DOSAGE AND ADMINISTRATION

Adults and children 12 years of age and over:  1 to 2 teaspoonfuls (5 mL to 10 mL), every
4 to 6 hours as needed;
Children 6 to under 12 years of age:  1/2 to 1 teaspoonful (2.5 mL to 5 mL), every 4 to 6
hours as needed;
Children under 6 years of age: as directed by a physician.
No recommended for children under 2 years of age.

HOW SUPPLIED

Dihydro-CP Syrup is supplied as a clear, dye free, sugar free, alcohol free syrup with a grape flavor in 16 fl oz (473 mL) bottles, NDC 60258-760-16.

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.

STORAGE:

Store at controlled room temperature, 15°-30°C (59°-86°F).

Call your doctor for medical advice about side effects.  You may report side effects to FDA at 1-800-FDA-1088.

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.

Rx Only

Manufactured for:
Cypress Pharmaceutical, Inc.
Madison, MS  39110

PIN051616 ISS. 01/10

PRODUCT PACKAGING:

The packaging below represents the labeling currently used:

Principal Display Panel and Side Panel for 473 mL label:

NDC 60258-760-16

DiHydro-CP Syrup

Antitussive/Antihistamine/Decongestant

Each teaspoonful (5 mL) for oral administration contains:
Dihydrocodeine Bitartrate..................................................7.5 mg
(WARNING: May be habit forming)
Chlorpheniramine Maleate....................................................2 mg
Pseudoephedrine HCl.........................................................15 mg

SUGAR FREE/ALCOHOL FREE/DYE FREE

Rx Only

CYPRESS PHARMACEUTICALS, INC.

16 fl oz (473 mL)

USUAL DOSAGE:  Adults and children 12 years of age and over:  1 to 2 teaspoonfuls
(5 mL to 10 mL), every 4 to 6 hours as needed.  Children 6 to under 12 years of age:
1/2 to 1 teaspoonful (2.5 mL to 5 mL), every 4 to 6 hours as needed.
Children under 6 years of age:  as directed by a physician.
Not recommended for children under 2 years of age.

For full prescribing information see attached insert.

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.

Store at controlled room temperature, 15°-30°C(59°-86°F).

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 container is not to be dispensed to the consumer.

Manufactured for:  Cypress Pharmaceutical, Inc., Madison, MS  39110

PSL051616  Rev. 01/10