Hydrocodone and homatropine

Take hydrocodone and homatropine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. If too much of hydrocodone and homatropine is taken for a long time, it may become habit-forming (causing mental or physical dependence) or cause an overdose.

hydrocodone and homatropine should come with a Medication Guide. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Swallow the tablet whole. Do not crush, break, or chew it.

Dosing

The dose of hydrocodone and homatropine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of hydrocodone and homatropine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For relief of cough:
    • Adults and children 12 years of age and older—1 tablet every 4 to 6 hours as needed. Do not take more than 6 tablets in 24 hours.
    • Children 6 to 11 years of age and older—One-half (1/2) tablet every 4 to 6 hours as needed. Do not take more than 3 tablets in 24 hours.
    • Children younger than 6 years of age—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of hydrocodone and homatropine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Decrease in the frequency of urination
• decrease in urine volume
• difficulty in passing urine (dribbling)
• painful urination

Get emergency help immediately if any of the following symptoms of overdose occur:

• Difficult or troubled breathing
• irregular, fast or slow, or shallow breathing
• pale or blue lips, fingernails, or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Nausea
• vomiting

• Drowsiness
• fear or nervousness
• itching skin or rash
• mood changes
• relaxed and calm
• sleepiness
• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

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.

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.

(hye droe KOE done & hoe MA troe peen)

Cough: Oral:

Children 6 to 11 years: Hydrocodone 2.5 mg/homatropine 0.75 mg (1/2 tablet or 2.5 mL) every 4 to 6 hours as needed (maximum: hydrocodone 15 mg/homatropine 4.5 mg [3 tablets or 15 mL] per 24 hours)

Children ≥12 years and Adolescents: Refer to adult dosing.

Store at 15°C to 30˚C (59˚F to 86˚F).

Refer to individual agents.

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (codeine, hydromorphone, levorphanol, morphine, oxycodone, oxymorphone).

• Respiratory depression: Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely for respiratory depression, especially during initiation. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

Disease-related concerns:

• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.

• Adrenocortical insufficiency: Use with caution in patients with adrenal insufficiency, including Addison disease.

• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction or acute pancreatitis; opioids may cause constriction of sphincter of Oddi.

• Delirium tremens: Use with caution in patients with delirium tremens.

• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure; exaggerated elevation of ICP may occur.

• Hepatic impairment: Use with caution in patients with severe hepatic impairment.

• Increased intraocular pressure/glaucoma: Use with caution in patients with increased intraocular pressure or glaucoma.

• Obesity: Use with caution in patients who are morbidly obese.

• Prostatic hyperplasia/urinary obstruction: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.

• Psychosis: Use with caution in patients with toxic psychosis.

• Renal impairment: Use with caution in patients with severe renal impairment.

• Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those having a substantially decreased respiratory reserve, hypoxia, hypercarbia, or preexisting respiratory depression, particularly when initiating therapy; critical respiratory depression may occur, even at therapeutic dosages.

• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Concurrent drug therapy issues:

• Benzodiazepines or other CNS depressants: [US Boxed Warning]: Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol.

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• CYP2D6 "poor metabolizers": Due to the role of CYP2D6 in the metabolism of hydrocodone to hydromorphone (an active metabolite with higher binding affinity to mu-opioid receptors compared to hydrocodone), patients with genetic variations of CYP2D6, including "poor metabolizers" or "extensive metabolizers," may have decreased or increased hydromorphone formation, respectively. Variable effects in positive and negative opioid effects have been reported in these patients; however, limited data exists to determine if clinically significant differences of analgesia and toxicity can be predicted based on CYP2D6 phenotype (Hutchinson, 2004; Otton, 1993; Zhou, 2009).

• Cachectic or debilitated patients: Use with caution in cachectic or debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages.

• Elderly: Use with caution in the elderly; may be more sensitive to adverse effects.

• Pediatric: Respiratory depression may occur even at therapeutic dosages; use with extreme caution in children.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP ["Inactive" 1997]; Zar 2007).

Other warnings/precautions:

• Abuse/misuse/diversion: Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists.

• Administration: Use an accurate measuring device; a household teaspoon is not an accurate measuring device and could lead to overdosage, which can result in serious adverse reactions.

• Cough: Appropriate use: Underlying cause of cough should be determined prior to prescribing.