The following Structured Product Label (SPL) was submitted to the FDA by Kvk-tech, Inc. for the product Hydrocodone Bitartrate And Homatropine Methylbromide (NDC 10702-150). This document serves as the official prescribing information, containing essential scientific data and clinical materials required for healthcare providers and patients.
This specific version of the label includes detailed information regarding boxed warning, description, clinical pharmacology, indications and usage, contraindications, warnings, precautions, adverse reactions, and other regulatory disclosures. Use the navigation below to review specific sections of the FDA submission.
WARNING: RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS
Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death (see WARNINGS, PRECAUTIONS – Drug Interactions). Avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol.
Hydrocodone bitartrate and homatropine methylbromide oral solution contains hydrocodone (dihydrocodeinone) bitartrate, a semisynthetic centrally-acting opioid antitussive. Homatropine methylbromide is included in a subtherapeutic amount to discourage deliberate overdosage.
Each hydrocodone bitartrate and homatropine methylbromide teaspoonful (5 mL) contains:
Hydrocodone Bitartrate, USP 5 mg
Homatropine Methylbromide, USP 1.5 mg
Hydrocodone bitartrate and homatropine methylbromide oral solution also contains: cherry flavor, FD&C Red #40, glycerin, hydrochloric acid, maltitol syrup, purified water, sodium benzoate, sorbitol, and sucralose. Hydrochloric acid and/or sodium hydroxide may be added to adjust pH.
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 (494.50), and may be represented by the following structural formula:
Homatropine methylbromide is 8-Azoniabicyclo [3.2.1]octane,3-[(hydroxyphenyl-acetyl)oxy]-8,8-dimethyl-,bromide, endo-; a white crystal or fine white crystalline powder, with a molecular weight of (370.29).
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- αand 6-β-hydroxymetabolites.
Hydrocodone bitartrate and homatropine methylbromide is indicated for the symptomatic relief of cough in adults and children 6 years of age and older.
Hydrocodone bitartrate and homatropine methylbromide should not be administered to patients who are hypersensitive to hydrocodone or homatropine methylbromide.
Risks from Concomitant Use with Benzodiazepines or other CNS Depressants
Concomitant use of opioids, including hydrocodone bitartrate and homatropine methylbromide, with benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedations, 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 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 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).
Respiratory Depression
The use of hydrocodone bitartrate and homatropine methylbromide 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 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 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.
Acute Abdominal Conditions
The administration of hydrocodone bitartrate and homatropine methylbromide or other opioids may obscure the diagnosis or clinical course of patients with acute abdominal conditions.
Pediatric Use
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 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 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).
General
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 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.
Information for Patients
Inform patients and caregivers that potentially fatal additive effects may occur if hydrocodone bitartrate and homatropine methylbromide 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 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 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.
Drug Interactions
The use of benzodiazepines, opioids, antihistamines, antipsychotics, anti-anxiety agents or other CNS depressants (including alcohol) concomitantly with hydrocodone bitartrate and homatropine methylbromide 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.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Studies of hydrocodone bitartrate and homatropine methylbromide in animals to evaluate the carcinogenic and mutagenic potential and the effect on fertility have not been conducted.
Pregnancy
Teratogenic Effects: Pregnancy Category C
Animal reproduction studies have not been conducted with hydrocodone bitartrate and homatropine methylbromide. It is also not known whether hydrocodone bitartrate and homatropine methylbromide can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Hydrocodone bitartrate and homatropine methylbromide should be given to a pregnant woman only if clearly needed.
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.
Labor and Delivery
As with all opioids, administration of hydrocodone bitartrate and homatropine methylbromide to the mother shortly before delivery may result in some degree of respiratory depression in the newborn, especially if higher doses are used.
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 hydrocodone bitartrate and homatropine methylbromide, 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.
Pediatric Use
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 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 should be used with caution in pediatric patients 6 years of age and older (see WARNINGS – Pediatric Use).
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 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 may produce dose-related respiratory depression by acting directly on brain stem respiratory centers (see OVERDOSAGE). Use of hydrocodone bitartrate and homatropine methylbromide 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 KVK-Tech, Inc. at 1-215-579-1842 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Hydrocodone bitartrate and homatropine methylbromide is a Schedule II opioid. Psychic dependence, physical dependence and tolerance may develop upon repeated administration of opioids; therefore, hydrocodone bitartrate and homatropine methylbromide should be prescribed and administered with caution. However, psychic dependence is unlikely to develop when hydrocodone bitartrate and homatropine methylbromide 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 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
One (1) tablet or 5 mL (1 teaspoonful) of the oral solution every 4 to 6 hours as needed; do not exceed six (6) tablets or 30 mL (6 teaspoonfuls) in 24 hours.
Children 6 to 11 Years of Age
One-half (1/2) tablet or 2.5 mL (1/2 teaspoonful) of the oral solution every 4 to 6 hours as needed; do not exceed three (3) tablets or 15 mL (3 teaspoonfuls) in 24 hours.
Hydrocodone bitartrate and homatropine methylbromide is available as a clear red colored, cherry flavored oral solution in:
Bottles of 16 fl.oz. (one pint) NDC 10702-150-16
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature.]
Manufactured by:
KVK-Tech, Inc.
110 Terry Drive
Newtown, PA 18940
Manufacturer’s Code: 10702
Item ID #: 6228/04 Rev.: 01/2017
What is the most important information I should know about Hydrocodone bitartrate and homatropine methylbromide oral solution?
o increased sleepiness o shallow breathing
o confusion o limpness
o difficulty breathing o your baby has difficulty breastfeeding
What is Hydrocodone bitartrate and homatropine methylbromide?
Who should not take Hydrocodone bitartrate and homatropine methylbromide?
Before you take Hydrocodone bitartrate and homatropine methylbromide, tell your healthcare provider about all of your medical conditions, including if you:
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Taking Hydrocodone bitartrate and homatropine methylbromide with certain other medicines can cause side effects or affect how well Hydrocodone bitartrate and homatropine methylbromide or the other medicines work. Do not start or stop other medicines without talking to your healthcare provider. Especially tell your healthcare provider if you:
How should I take Hydrocodone bitartrate and homatropine methylbromide?
• Take Hydrocodone bitartrate and homatropine methylbromide exactly as your healthcare provider tells you to take it.
• Your healthcare provider will tell you how much Hydrocodone bitartrate and homatropine methylbromide to take and when to take it. Do not change your dose without talking to your healthcare provider.
• Ask your pharmacist to give you a measuring device to help you measure the correct amount of Hydrocodone bitartrate and homatropine methylbromide. Do not use a household teaspoon to measure your medicine. You may accidently take too much. If you take too much Hydrocodone bitartrate and homatropine methylbromide, call your healthcare provider or go to the nearest hospital emergency room right away.
What should I avoid while taking Hydrocodone bitartrate and homatropine methylbromide?
What are the possible side effects of Hydrocodone bitartrate and homatropine methylbromide?
Hydrocodone bitartrate and homatropine methylbromide may cause serious side effects, including:
• sleepiness
• confusion
• nausea and vomiting
• difficulty urinating
• trouble breathing
These are not all the possible side effects of Hydrocodone bitartrate and homatropine methylbromide. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store Hydrocodone bitartrate and homatropine methylbromide?
General information about the safe and effective use of Hydrocodone bitartrate and homatropine methylbromide.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Hydrocodone bitartrate and homatropine methylbromide for a condition for which it was not prescribed. Do not give Hydrocodone bitartrate and homatropine methylbromide to other people, even if they have the same symptoms that you have.
You can ask your pharmacist or healthcare provider for information about Hydrocodone bitartrate and homatropine methylbromide that is written for health professionals.
What are the ingredients in Hydrocodone bitartrate and homatropine methylbromide?
Active ingredient: hydrocodone bitartrate and homatropine methylbromide.
Inactive ingredients in Hydrocodone bitartrate and homatropine methylbromide oral solution:cherry flavor, FD&C Red #40, glycerin, hydrochloric acid, maltitol syrup, purified water, sodium benzoate, sorbitol, and sucralose. Hydrochloric acid and/or sodium hydroxide may be added to adjust pH.
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Manufactured By:
KVK-TECH, INC.
110 Terry Drive
Newtown, PA 18940
Item ID #: 6228/04 Rev: 01/17
NDC 10702-150-16
Hydrocodone Bitartrate Homatropine Methylbromide Oral Solution CII
5 mg/1.5 mg per 5 ml
Pharmacist: Dispense the accompanying Medication Guide to each patient.
Each 5 ml (teaspoonfil) contains:
Hydrocodone Bitartrate, USP ................. 5 mg
Homatropine Methylbrominde, USP ...... 1.5 mg
Usual Dosage: Read accompanying product information
Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required).
Store at 25oC (77oF);excursion permitted to 15o to 30oC (59o to 86oF). [See USP Controlled Room Temperature].
Rx only 16 fl. oz. (473 ml)
KVK-TECH
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