Hycomine

Hycomine is part of the drug classes:

• Opium alkaloids and derivatives

• Sympathomimetics

Hydrocodone is a semisynthetic narcotic antitussive and analgesic with multiple actions qualitatively similar to those of codeine. The precise mechanism of action of hydrocodone and other opiates is not known; however, hydrocodone is believed to act directly on the cough center. In excessive doses, hydrocodone, like other opium derivatives, will depress respiration. The effects of hydrocodone in therapeutic doses on the cardiovascular system are insignificant. Hydrocodone can produce miosis, euphoria, physical and physiological dependence.

Following a 10 mg oral dose of hydrocodone administered to five adult male 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 pattern of metabolism including 0-demethylation, N-demethylation and 6-keto reduction to the corresponding 6-α- and 6-β-hydroxymetabolites.

Phenylpropanolamine effects its vasoconstrictor activity by releasing noradrenaline from sympathetic nerve endings, and from direct stimulation of α–adrenoreceptors of blood vessels.

May be habit forming. Hydrocodone can produce 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 Hycomine 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).

Respiratory Depression

Hycomine produces dose-related respiratory depression by directly acting on brain stem respiratory centers. If respiratory depression occurs, it may be antagonized by the use of naloxone hydrochloride and other supportive measures when indicated.

Head Injury and Increased Intracranial Pressure

The respiratory depression properties 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 Hycomine or other narcotics may obscure the diagnosis or clinical course of patients with acute abdominal conditions.

Pediatric Use

In young children, as well as adults, the respiratory center is sensitive to the depressant action of narcotic cough suppressants in a dose-dependent manner. Benefit to risk ratio should be carefully considered especially in children with respiratory embarrassment (e.g., croup).

Phenylpropanolamine

Hypertensive crises can occur with concurrent use of phenylpropanolamine and monoamine oxidase (MAO) inhibitors, indomethacin or with beta-blockers and methyldopa.

If a hypertensive crisis occurs, these drugs should be discontinued immediately and therapy to lower blood pressure should be instituted immediately. Fever should be managed by means of external cooling.

Signs and Symptoms

Serious overdosage with Hycomine 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.

The signs and symptoms of overdosage of the individual components of Hycomine (hydrocodone bitartrate and phenylpropanolamine hydrochloride) may be modified in varying degrees by the presence of other active ingredients. Overdosage with phenylpropanolamine alone may result in tremor, restlessness, increased motor activity, agitation and hallucinations.

Treatment

Primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent 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 hydrochloride should be administered, preferably by the 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 measures should be employed as indicated. Gastric emptying may be useful in removing absorbent drug.

Hycomine Syrup (5 mg hydrocodone bitartrate, USP and 25 mg phenylpropanolamine hydrochloride, USP – per 5 mL teaspoonful) is available as an orange-colored, cherry-flavored syrup in bottles as follows:

One Pint (473.2 mL):     NDC 63481-246-16

Hycomine Pediatric Syrup (2.5 mg hydrocodone bitartrate, USP and 12.5 mg phenylpropanolamine hydrochloride, USP – per 5 mL teaspoonful) is available as a green-colored, cherry-flavored syrup in bottles as follows:

One Pint (473.2 mL):     NDC 63481-247-16

Store in controlled room temperature 15˚-30˚C (59˚-86˚F).

Oral prescription where permitted by State law.

CAUTION: Federal (USA) law prohibits dispensing without a prescription.

Manufactured for:
Endo Pharmaceuticals Inc.
Chadds Ford, Pennsylvania 19317

Manufactured by:
DuPont Pharma
Wilmington, Delaware 19880

Hycomine®is a Registered Trademark of Endo Pharmaceuticals Inc.

                                   Copyright © Endo Pharmaceuticals Inc. 1997

Printed in U.S.A.                                                                              6480/August, 1997