Hydromet Solution
FDA Label NDC 0472-1030

Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution contains hydrocodone (dihydrocodeinone) bitartrate, USP, a semisynthetic centrally-acting opioid antitussive. Homatropine methylbromide, USP is included in a subtherapeutic amount to discourage deliberate overdosage.

Each teaspoonful (5 mL) contains:

Hydrocodone Bitartrate, USP ........................ 5 mg

Homatropine Methylbromide, USP ............... 1.5 mg

Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution also contains: artificial cherry flavor, anhydrous citric acid, D&C Red #33, FD&C Blue #1, FD&C Red #40, methylparaben, propylene glycol, purified water, saccharin sodium, sodium benzoate, sodium citrate dihydrate, and sucrose.

The hydrocodone component is 4,5α-epoxy-3-methoxy-17-methylmorphinan-6-one tartrate (1:1) hydrate (2:5), a fine white crystal or crystalline powder, which is derived from the opium alkaloid, thebaine, has a molecular weight of 494.49, and may be represented by the following structural formula:

Homatropine methylbromide, USP is a 3α-hydroxy-8-methyl-1αH, 5αH-tropanium bromide mandelate; a white crystal or fine white crystalline powder, with a molecular weight of 370.28.

Hydrocodone is a semisynthetic opioid 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 O-demethylation, N-demethylation and 6-keto reduction to the corresponding 6-α- and 6-ß-hydroxymetabolites.

Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution is indicated for the symptomatic relief of cough in adults and children 6 years of age and older.

Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution should not be administered to patients who are hypersensitive to hydrocodone or homatropine methylbromide.

Concomitant use of opioids, including Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution, with benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Because of these risks, avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol (see PRECAUTIONS - Drug Interactions).

Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. Because of similar pharmacologic properties, it is reasonable to expect similar risk with concomitant use of opioid cough medications and benzodiazepines, other CNS depressants, or alcohol.

Advise both patients and caregivers about the risks of respiratory depression and sedation if Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution is used with benzodiazepines, alcohol, or other CNS depressants (see PRECAUTIONS - Information for Patients).

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 Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution, and it should be prescribed and administered with the same degree of caution appropriate to the use of other opioid drugs (see DRUG ABUSE AND DEPENDENCE).

The use of Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution is not recommended for use in children less than 6 years of age because of the risk of fatal respiratory depression (see ADVERSE REACTIONS – Respiratory Depression). Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution 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.

The respiratory depression properties of opioids and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure. Furthermore, opioids produce adverse reactions which may obscure the clinical course of patients with head injuries.

The administration of Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution or other opioids may obscure the diagnosis or clinical course of patients with acute abdominal conditions.

In pediatric patients, as well as adults, the respiratory center is sensitive to the depressant action of opioid cough suppressants in a dose-dependent manner. Caution should be exercised when administering Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution to pediatric patients 6 years of age and older because of the potential for fatal respiratory depression. Overdose or concomitant administration of Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution with other respiratory depressants may increase the risk of respiratory depression in pediatric patients. Benefit to risk ratio should be carefully considered especially in the pediatric population with respiratory embarrassment (e.g., croup) (see PRECAUTIONS).

Safety and effectiveness of hydrocodone bitartrate and homatropine methylbromide in pediatric patients under six have not been established. The use of Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution in children less than 6 years of age has been associated with cases of fatal respiratory depression (see ADVERSE REACTIONS – Respiratory Depression). Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution should be used with caution in pediatric patients 6 years of age and older (see WARNINGS – Pediatric Use).

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

Special Risk Patients

Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution should be given with caution to certain patients such as the elderly or debilitated, and those with severe impairment of hepatic or renal functions, hypothyroidism, Addison’s disease, prostatic hypertrophy or urethral stricture, asthma, and narrow-angle glaucoma.

Inform patients and caregivers that potentially fatal additive effects may occur if Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution is used with benzodiazepines or other CNS depressants, including alcohol. Because of this risk, patients should avoid concomitant use of Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution with benzodiazepines or other CNS depressants, including alcohol (see WARNINGS, PRECAUTIONS - Drug Interactions).

Hydrocodone may produce marked drowsiness and impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. The patient using Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution should be cautioned accordingly.

Patients should be advised to measure Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution with an accurate measuring device. A household teaspoon is not an accurate measuring device and could lead to overdosage, especially when a half a teaspoon is measured. A pharmacist can recommend an appropriate measuring device and can provide instructions for measuring the correct dose. Keep out of the reach of children.

The use of benzodiazepines, opioids, antihistamines, antipsychotics, anti-anxiety agents, or other CNS depressants (including alcohol) concomitantly with Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution may cause an additive CNS depressant effect, profound sedation, respiratory depression, coma, and death and should be avoided (see WARNINGS).

The use of MAO inhibitors or tricyclic antidepressants with hydrocodone preparations may increase the effect of either the antidepressant or hydrocodone.

Studies of Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution in animals to evaluate the carcinogenic and mutagenic potential and the effect on fertility have not been conducted.

Pregnancy Category C. Animal reproduction studies have not been conducted with Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution. It is also not known whether Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution should be given to a pregnant woman only if clearly needed.

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.

As with all opioids, administration of Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution to the mother shortly before delivery may result in some degree of respiratory depression in the newborn, especially if higher doses are used.

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 Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution, 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.

Central Nervous System

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

Gastrointestinal System

Nausea and vomiting may occur; they are more frequent in ambulatory than in recumbent patients. Prolonged administration of Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution may produce constipation.

Genitourinary System

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

Respiratory Depression

Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution may produce dose-related respiratory depression by acting directly on brain stem respiratory centers (see OVERDOSAGE). Use of Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution in children less than 6 years of age has been associated with fatal respiratory depression. Overdose with hydrocodone bitartrate and homatropine methylbromide in children 6 years of age and older, in adolescents, and in adults has been associated with fatal respiratory depression. Postmarketing events seen in children under 6 years of age include accidental overdose, bronchopneumonia, coma, cyanosis, death, death neonatal, dyspnea, pulmonary edema, respiratory arrest, and respiratory depression. Postmarketing events seen in patients older than 6 years of age include accidental overdose, cardio-respiratory arrest, death due to drug toxicity, non-accidental overdose, and overdose.

Dermatological

Skin rash, pruritus.

To report SUSPECTED ADVERSE REACTIONS, contact Actavis at 1-800-432-8534 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution is a Schedule II opioid. Psychic dependence, physical dependence and tolerance may develop upon repeated administration of opioids; therefore, Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution should be prescribed and administered with caution. However, psychic dependence is unlikely to develop when Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution is used for a short time for the treatment of cough. Physical dependence, the condition in which continued administration of the drug is required to prevent the appearance of a withdrawal syndrome, assumes clinically significant proportions only after several weeks of continued oral opioid use, although some mild degree of physical dependence may develop after a few days of opioid therapy.

Signs and Symptoms

Serious overdosage with hydrocodone 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 ingestion of very large amounts of Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution may, in addition, result in acute homatropine intoxication.

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 opioid antagonist naloxone hydrochloride is a specific antidote for respiratory depression which may result from overdosage or unusual sensitivity to opioids 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 unabsorbed drug.

It is important that Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution is measured with an accurate measuring device (see PRECAUTIONS – Information for Patients). A household teaspoon is not an accurate measuring device and could lead to overdosage, especially when a half a teaspoon is to be measured. It is strongly recommended that an accurate measuring device be used. A pharmacist can provide an appropriate measuring device and can provide instructions for measuring the correct dose.

Adults and Adolescents 12 Years of Age and Older

5 mL (1 teaspoonful) of the oral solution every 4 to 6 hours as needed; do not exceed 30 mL (6 teaspoonfuls) in 24 hours.

Children 6 to 11 Years of Age

2.5 mL (1/2 teaspoonful) of the oral solution every 4 to 6 hours as needed; do not exceed 15 mL (3 teaspoonfuls) in 24 hours.

Hydrocodone Bitartrate and Homatropine Methylbromide Oral Solution is a red colored, cherry flavored oral solution containing 5 mg hydrocodone bitartrate, USP and 1.5 mg homatropine methylbromide, USP per 5 mL, and is available in one pint (473 mL) bottles (NDC 0472-1030-16).

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

Dispense in a tight, light-resistant container as defined in the USP.

Oral prescription where permitted by State Law.

Manufactured by:
G&W Laboratories, Inc.
111 Coolidge Street
South Plainfield, NJ 07080 USA

Distributed by:
Actavis Pharma, Inc.
Parsippany, NJ 07054 USA

I602-1090 GW7167
Rev. 01/07

This Medication Guide has been approved by the U.S. Food and Drug Administration.