Rx Only

DESCRIPTION

Each immediate release, white, dye-free, capsule-shaped tablet contains:

Hydrocodone Bitartrate..........................................................................2.5 mg

                          (WARNING:  May be habit forming)

Guaifenesin.........................................................................................300 mg

Hydrocodone bitartrate is an opioid analgesic and antitussive.  It occurs as fine white crystals or 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). 

Guaifenesin is an expectorant.  Its chemical name is 3-2(2-methoxyphenoxy)-1,2-propanediol.

Inactive ingredients include calcium phosphate, lactose monohydrate, magnesium stearate, methycellulose, microcrystalline cellulose, povidone, and stearic acid.

CLINICAL PHARMACOLOGY

This product contains hydrocodone bitartrate, a semi-synthetic centrally-acting narcotic antitussive, and guaifenesin, an expectorant, for oral administration.

Clinical trials have proven hydrocodone bitartrate to be an effective antitussive agent which is pharmacologically two to eight times as potent as codeine.  At equi-effective doses, its sedative action is greater than codeine.  The precise mechanism of action of hydrocodone and other opiates is not known: however, hydrocodone is believed to act by directly depressing the cough center.  In excessive doses hydrocodone, like other opium derivatives, can depress respiration.  The effects of hydrocodone in therapeutic doses on the cardiovascular system is insignificant.  The constipation effects of hydrocodone are much weaker than that of morphine and no stronger tha that of codeine.  hydrocodone can produce miosis, euphoria, physical and psychological dependence.  At therapeutic antitussive doses, it does exert analgesic effects.  Following a 10 mg oral dose of hydrocodone administered to five male human 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 patttern of metabolism, including 0-demethylation, N-demethylation and 6-keto reduction to the corresponding 6-α- and 6-β-hydroxy- metabolites.

The exact mechansim of action is not established but guaifenesin is believed to act by stimulating receptors in the gastric mucosa that initiate a reflex secretion of respiratory tract fluid, thereby increasing the volume and decreasing the viscosity of bronchial secretions.  Studies with guaifenesin indicate that it is rapidly absorbed from the gastrointestinal tract and has a half life on one hour.

INDICATIONS AND USAGE

For the temporary relief of dry, non-productive cough associated with upper and lower respiratory tract congestion.

CONTRAINDICATIONS

Hypersensitivity to hydrocodone or guaifenesin.  Patients known to be hypersensitive to other opioids may exhibit cross sensitivity to this product.  Hydrocodone is contraindicated in the presence of increased intracranial pressure and whenever ventilatory function is depressed; the depression may be exacerbated.

This medication should not be used when diarrhea asociated with pseudomembranous, colitis caused by cephalosporins, lincormycins (possibly including topical clindamycin), or penicillins exist.  Furthermore, opiods should not be administered when diarrhea is present caused by poisoning, until the toxic material has been eliminated from the gastrointestinal tract.  Opioid analgesic may slow elimination of the toxic material, thereby worsening and/or prolonging the diarrhea.

WARNINGS

May be habit forming.  Hydrocodone can product drug dependence of the morphine type and therefore, has the potential for being abused.  Psychic dependence, physical dependence and tolerance may develop upon repeated administration of this product and it should be prescribed and administered with the same degree of caution appropriate to the use of other narcotic drugs (see Drug Abuse and Dependence section).

Respiratory Depressions:

This product produces dose-related respiratory depression by directly acting on the brain stem respiratory centers.  Hydrocodone also affects the center that controls respiratory rhythm, and may produce irregular and periodic breathing.  If respiratory depression occurs, it may be antagonized by the use of naloxone and other supportive measures when indicated.

Head Injury and Increased Intracranial Pressure:

The respiratory depressant properties of narcotics and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracrainial lesions or a pre-existing 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 this product or other opioids may obscure the diagnosis or clinical course of patients with acute abdominal conditions.

PRECAUTIONS

General:

The hydrocodone in this product may exhibit additive effects with other CNS depressants, including alcohol.  Respiratory depression can be a hazard so caution should be used, especially in patients with chronic obstructive pulmonary disease.

Before prescribing medication to suppress or modify a cough, it is important to ascertain that the underlying cause of the cough is identified, that modification of the cough does not increase the risk of clinical or physiologic complications, and that appropriate therapy for the primary disease is provided.

Special Risk Patients:

As with any narcotic analgesic agent, this product 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.

Information for Patients:

Hydrocodone may cause drowsiness and ambulatory patients who operate machinery or motor vehicles should be cautioned accordingly.

Drug Interactions:

Patients receiving other narcotic analgesics, general anesthetics, phenothiazines or other tranquillizers, sedative hypnotics or other CNS depressants (including alcohol) concomitantly with hydrocodone may exhibit an additive CNS depression.  When such combined therapy is contemplated, the dose of one or both agents should be reduced.  (See WARNINGS.)

The use of MAO inhibitors or tricyclic antidepressants with hydrocodone preparations may increase the effect of either the antidepressant or hydrocodone.  The concurrent use of anticholinergics with hydrocodone may produce paralytic ileus.

Laboratory Test Interactions:

Guaifenesin may increase renal clearance for urates and thereby lower serum uric acid levels.  Guaifenesin may produce an increase in urinary 5-hydroxyindoleacetic acid and may therefore interfere with the interepreation of the test for the diagnosis of carcinoid syndrome.  It may also falsely elevate the VMA test for catechols.  Administration of this product should be discontinued 48 hours prior to the collection of urine specimens for such tests.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Carcinogenicity, mutagenicity and reproduction studies have not been conducted with this product.

Usage in Pregnancy:  Pregnancy Category C.

Hydrocodone 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.  It is not known whether this product can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity.  This product should be used during pregnancy only if the potential benefits justify the potential risk to the fetus.

Labor and Delivery:

As with all narcotics, administration of the product to the mother shortly before delivery may result in some degree of respiratory depression in the newborn especially if high doses are used.

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 not consensus on the best method of managing withdrawal.

Chlorpromazine 0.7-1.0 mg/kg q 6h, phenobarbital 2 mg/kg q 6h, and paregoric 2-4 drops/kg q 4h, have been used to treat withdrawal symptoms in infants.  The duration of therapy is 4 to 28 days, with the dosages decreased as tolerated.

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 this product, a decision should be made whether to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use:

Narcotic antitussives are not recommended for use in children under six years of age.  Children under six years may be more susceptible to respiratory arrest, coma and death.  No age-specific problems related to guaifenesin have been documented in the pediatric population to date.

Geriatric Use:

Geriatric patients may be more susceptible to the effects, especially the respiratory depressant effects, of opioids.  Also, geriatric patients are more likely to have prostatic hypertrophy or obstruction and age-related renal function impairment, and are more likely to be adversely affected by opioidinduced urinary retention.  In addition, geriatric patients may metabolize or eliminate this medication more slowly than younger adults.  Lower doses or longer dosing intervals than those usually recommended for adults may be required, and are usually therapeutically effective, for these patients.

No age-specific problems related to guaifenesin have been documented in the geriatric population to date.

ADVERSE REACTIONS

Adverse reactions include drowsiness, lassitude, nausea, giddiness, constipation, respiratory depression and addiction.

The most frequently observed adverse reactions include light-headedness, dizziness, drowsiness, sedation, nausea and vomiting.  These effects seem to be more prominent in ambulatory than in nonambulatory patients, and some of these adverse reactions my be alleviated if the patient lies down

Respiratory System:

Hydrocodone produces dose-related respiratory depression by acting directly on brain stem respiratory centers.

Cardiovascular System:

Hypertension, postural hypotension and palpitations.

Genitourinary System:

Ureteral spasm, spasm of vesical sphincters and urinary retention have been reported with opiates.

Central Nervous System:

Sedation, drowsiness, mental clouding, lethargy, impairment of mental and physical performance, anxiety, fear, dysphoria, dizziness, psychic dependence, mood changes and blurred vision.

Gastrointestinal System:

Nausea and vomiting occur more frequently in ambulatory than in recumbent patients.

DRUG ABUSE AND DEPENDENCE

Special care should be exercised in prescribing hydrocodone for emotionally unstable patients and for those witha a history of drug misuse.  Such patients should be closely supervised when long-term therapy is contemplated.

This product is a Schedule III narcotic.  Psychic dependence, physical dependence and tolerance may develop upon repeated administration of narcotics; therefore, EndaCof Tab Tablets should always be prescribed and administered with caution.  Physical dependence is the condition in which continued administration of the drug is required to prevent the appearance of a withdrawal syndrome. 

Patients physically dependent on opioids will develop an abstinence syndrome upon abrupt discontinuation of the opioid or following the administration of a narcotic antagonist.  The character and severity of the withdrawal symptoms are related to the degree of physical dependence.  Manifestations of opioid withdrawal are similar to but milder than that of morphine and include lacrimation, rhinorrha, yawning, sweating, restlessness, dilated pupils, anorexia, gooseflesh, irritability, and tremor.  In more severe forms, nausea, vomiting, intestinal spasm and diarrhea, increased heart rate and blood pressure, chills, and pains in bones and muscles of the back and extremities may occur.  Peak effects will usually be apparent at 48 to 72 hours.

Treatment of withdrawal is usually managed by providing sufficient quantities of an opioid to suppress severe withdrawal symptoms and then gradually reducing the dose of opioid over a period of several days.

OVERDOSAGE

Sings and Symptoms:

Seriouos overdosage with EndaCof Tab Tablets 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.

Overdosage withguaifenesin is unlikely to produce toxic effects since its toxicity is low.  Guaifenesin, when administered by stomach tube to test animals in doses up to 5 g/kg, produced no signs of toxicity.

Treatment:

Treatment of acute overdosage would probably be based upon treating the patient for hydrocodone toxicity as follows:  primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patient airway and the institution of assisted or controlled ventilation.  The narcotic antagonist naloxone hydrochloride is a specific antidote for respiratory depression which may result from overdosage or unusual sensitivity to narcotics, including hydrocodone.  Therefore, an appropriate dose of naloxone should be administered, preferably by intravenous route, simultaneously with efforts at respiratory resuscitation.  For further information, see full prescribing information for naloxone hydrochloride.  An antagonist should not be administered in the absence of clinically significant respiratory depression.  Oxygen, intravenous fluids, vasopressors and other supportive measure should be employed as indicated.  Gastric emptying may be useful in removing unabsorbed drug.  Activated charcoal may be of benefit.

DOSAGE AND ADMINISTRATION

Adults and Chidren over 12 years:

One or two tablets every 4-6 hours, not to exceed 8 tablets in 24 hour period.

Children 6-12 years:

One tablet every 4-6 hours, not to exceed 4 tablets in 24 hours period.

Narcotic antitussives are not recommended for use in children under 6 years of age.  Children under 6 years of age may be more susceptible to respiratory arrest, coma and death.

HOW SUPPLIED

EndaCof Tab is white, capsule-shaped tablets debossed "LL 35" on one side scored on the opposite side.  EndaCof Tab is supplied in bottles of 30 tablets, NDC 54868-5492-0.

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

Rx Only

Dispense in tight, light-resistant containers as defined in the USP/NF.

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

Manufactured by:
Sovereign Pharmaceuticals, Ltd.,
Fort Worth, TX  76118

Distrubuted by:
Larken Laboratories,
madisin, MS  39110

500200
Iss. 4/2005


Additional barcode labeling by:
Physicians Total Care, Inc.
Tulsa, Oklahoma       74146

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL