CENTUSSIN DHC Liquid

NDC 23359-018-16
Rx Only

CV

DESCRIPTION:
Each 5 mL (one teaspoonful) for oral administration contains:
Dihydrocodeine Bitartrate*........................ 3 mg
*(WARNING- May be habit forming)
Brompheniramine Maleate........................ 4 mg
Phenylephrine Hydrochloride................... 7.5 mg

CENTUSSIN DHC Liquid also contains: Glycerin, Propylene Glycol, Sorbitol, Citric Acid, Sodium Citrate,
Sodium Saccharin, Grape Flavor, Purified Water.

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). It has the following structural formula:

Brompheniramine Maleate is an antihistamine having the chemical name, 2-Pyridinepropanamine, γ-(4-bromophenyl)-N, N-dimethyl-, (±)-,(Z)-2-butenedioate (1:1). With the following structure:

Phenylephrine hydrochloride is an orally effective nasal decongestant. Chemically it is (-)-m-Hydroxy-α-[(methylamino)methyl]benzyl alcohol hydrochloride. Its chemical structure 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. Brompheniramine maleate 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 among the most suitable agents for daytime use, but a significant proportion of patients do experience this effect. 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.

INDICATIONS AND USAGE

CENTUSSIN 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 ponents listed above, or in any situation where opioids are  contraindicated including significant respiratory depression (in unmonitored settings or in the bsence of resuscitation equipment), acute or severe bronchial asthma or hypercapnia, and paralytic ileus.  Antihistamines and sympathomimetics re ontraindicated in patients receiving antihypertensive or  antidepressant drugs containing monoamine oxidase (MAO) inhibitors. Antihistamines hould not be used to treat lower respiratory tract symptoms or be given to premature or newborn infants.  Sympathomimetic agents are ontraindicated in patients with severe hypertension, severe coronary  artery disease, patients with narrow angle glaucoma, bronchial asthma, rinary 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. CENTUSSIN 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 CENTUSSIN DHC Liquid should be given the following information:

1. Patients should be advised that CENTUSSIN DHC Liquid may impair the mental or physical abilities required for the performance of potentialy 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 CENTUSSIN DHC Liquid without consulting the prescribing professional.
4. Patients should not combine CENTUSSIN 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 CENTUSSIN DHC Liquid is a potential drug of abuse. They should protect it 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 CENTUSSIN DHC Liquid. It is also not known whether this combination product can cause fetal harm when administered to pregnant women or can affect reproduction capactiy 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:

CENTUSSIN 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:

CENTUSSIN DHC Liquid should be given with caution to the elderly.

Hepatic Impairment: CENTUSSIN 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: CENTUSSIN DHC Liquid should be used with caution and at 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 CENTUSSIN DHC Liquid include, lassitude, nausea, giddiness, dryness of mouth, blurred vision, cardiac palpitations, flushing, increase 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 V. 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 CENTUSSIN 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 CENTUSSIN 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 or 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

A clear colored liquid with a grape flavor supplied in 16 oz. bottles (NDC 23359-018-16).

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.

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 15o-30oC (59o-86oF). [See USP Controlled Room Temperature.]

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

Rx Only

Manufactured for:
Centurion Labs, LLC
Birmingham, AL 35236

Rev. 11/09

PRODUCT PACKAGING:

The packaging below represents the labeling currently used:

NDC 23359-018-16

CENTUSSIN DHC LIQUID

ANTITUSSIVE
ANTIHISTAMINE
DECONGESTANT

EACH TEASPOONFUL (5 mL) CONTAINS:
Dihydrocodeine Bitartrate*........ 3 mg
*(WARNING-May be habit forming)
Brompheniramine Maleate....... 4 mg
Phenylephrine HCl................ 7.5 mg

Grape Flavor

CV

16 fl oz. (473 mL)

Rx Only

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.

Store at 15o-30oC (59o-86oF). [See USP Controlled Room Temperature.]

Rx Only

Rev. 11/09

Manufactured for:
CENTURION LABS, LLC
LEADING PHARMACEUTICALS
Birmingham, AL 35236