Hydrocodone Bitartrate and Homatropine Methylbromide

1 INDICATIONS AND USAGE Hydrocodone Bitartrate and Homatropine Methylbromide Tablets are indicated for the symptomatic relief of cough in adult patients 18 years of age and older. Limitations of Use: Not indicated for pediatric patients under 18 years of age [ see Use in Specific Populations (8.4) ]. Contraindicated in pediatric patients less than 6 years of age [ see Contraindications (4) ]. Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [ see Warnings and Precautions (5.1) ] , reserve Hydrocodone Bitartrate and Homatropine Methylbromide Tablets for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made. Hydrocodone Bitartrate and Homatropine Methylbromide Tablets is a combination of hydrocodone, an opioid agonist, and homatropine, a muscarinic antagonist, indicated for the symptomatic relief of cough in adult patients 18 years of age and older. ( 1 ) Limitations of Use (1 ) Not indicated for pediatric patients under 18 years of age. Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve Hydrocodone Bitartrate and Homatropine Methylbromide Tablets for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made.

2 DOSAGE AND ADMINISTRATION Adults 18 years of age and older : One (1) tablet every 4 to 6 hours as needed; not to exceed six (6) tablets in 24 hours. ( 2.2 ) Do not increase the dose or dosing frequency. ( 2.1 ) Prescribe for the shortest duration consistent with treatment goals. ( 2.3 ) Reevaluate patients with unresponsive cough in 5 days or sooner for possible underlying pathology. ( 2.3 ) Reevaluate patient prior to refilling. ( 2.3 ) 2.1 Important Dosage and Administration Instructions Administer Hydrocodone Bitartrate and Homatropine Methylbromide Tablets by the oral route only. Advise patients not to increase the dose or dosing frequency of Hydrocodone Bitartrate and Homatropine Methylbromide Tablets because serious adverse events such as respiratory depression may occur with overdosage [ see Warnings and Precautions (5.2) , Overdosage (10) ]. The dosage of Hydrocodone Bitartrate and Homatropine Methylbromide Tablets should not be increased if cough fails to respond; an unresponsive cough should be reevaluated for possible underlying pathology [ see Dosage and Administration (2.3) , Warnings and Precautions (5.4) ]. 2.2 Recommended Dosage Adults 18 years of age and older : One (1) tablet every 4 to 6 hours as needed; not to exceed six (6) tablets in 24 hours. 2.3 Monitoring, Maintenance, and Discontinuation of Therapy Prescribe Hydrocodone Bitartrate and Homatropine Methylbromide Tablets for the shortest duration that is consistent with individual patient treatment goals [ see Warnings and Precautions (5.1) ] . Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy [ see Warnings and Precautions (5.2) ] . Reevaluate patients with unresponsive cough in 5 days or sooner for possible underlying pathology, such as foreign body or lower respiratory tract disease [ see Warnings and Precautions (5.4) ]. If a patient requires a refill, reevaluate the cause of the cough and assess the need for continued treatment with Hydrocodone Bitartrate and Homatropine Methylbromide Tablets, the relative incidence of adverse reactions, and the development of addiction, abuse, or misuse [ see Warnings and Precautions (5.1) ]. Do not abruptly discontinue Hydrocodone Bitartrate and Homatropine Methylbromide Tablets in a physically-dependent patient [ see Drug Abuse and Dependence (9.3) ]. When a patient who has been taking Hydrocodone Bitartrate and Homatropine Methylbromide Tablets regularly and may be physically dependent no longer requires therapy with Hydrocodone Bitartrate and Homatropine Methylbromide Tablets, taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal. If the patient develops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both.

4 CONTRAINDICATIONS Hydrocodone Bitartrate and Homatropine Methylbromide Tablets is contraindicated for: All pediatric patients younger than 6 years of age [ see Warnings and Precautions ( 5.2 , 5.3 ) Use in Specific Populations (8.4) ]. Significant respiratory depression [ see Warnings and Precautions (5.2) ]. Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [ see Warnings and Precautions (5.4) ]. Known or suspected gastrointestinal obstruction, including paralytic ileus [ see Warnings and Precautions (5.9) ]. Hypersensitivity to hydrocodone, homatropine, or any of the inactive ingredients in Hydrocodone Bitartrate and Homatropine Methylbromide Tablets [ see Adverse Reactions (6) ]. Children younger than 6 years of age. ( 4 ) Significant respiratory depression. ( 4 ) Acute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipment. ( 4 ) Known or suspected gastrointestinal obstruction, including paralytic ileus. ( 4 ) Hypersensitivity to hydrocodone, homatropine, or any of the inactive ingredients in Hydrocodone Bitartrate and Homatropine Methylbromide Tablets. ( 4 )

Not available.

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in labeling: Addiction, abuse, and misuse [ see Warnings and Precautions (5.1) , Drug Abuse and Dependence (9.3) ] Life-threatening respiratory depression [ see Warnings and Precautions (5.2 , 5.3 , 5.4 , 5.8 ) and Overdosage (10) ] Accidental overdose and death due to medication errors [ see Warnings and Precautions (5.5) ] Decreased mental alertness with impaired mental and/or physical abilities [ see Warnings and Precautions (5.6) ] Interactions with benzodiazepines and other CNS depressants [ see Warnings and Precautions ( 5.8 ), and Drug Interactions (7.1) , ( 7.4) ] Paralytic ileus, gastrointestinal adverse reactions [ see Warnings and Precautions (5.9) ] Increased intracranial pressure [ see Warnings and Precautions (5.10) ] Obscured clinical course in patients with head injuries [ see Warnings and Precautions (5.10) ] Seizures [ see Warnings and Precautions (5.11) ] Severe hypotension [ see Warnings and Precautions (5.12) ] Neonatal Opioid Withdrawal Syndrome [ see Warnings and Precautions (5.13) ] Adrenal insufficiency [ see Warnings and Precautions (5.14) ] The following adverse reactions have been identified during clinical studies, in the literature, or during post-approval use of hydrocodone and/or homatropine. Because these reactions may be reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The most common adverse reactions to Hydrocodone Bitartrate and Homatropine Methylbromide Tablets include: Sedation (somnolence, mental clouding, lethargy), impaired mental and physical performance, lightheadedness, dizziness, headache, dry mouth, nausea, vomiting, and constipation. Other reactions include: Anaphylaxis : Anaphylaxis has been reported with hydrocodone, one of the ingredients in Hydrocodone Bitartrate and Homatropine Methylbromide Tablets. Body as a whole : Coma, death, fatigue, falling injuries, lethargy. Cardiovascular : Peripheral edema, increased blood pressure, decreased blood pressure, tachycardia, chest pain, palpitation, syncope, orthostatic hypotension, prolonged QT interval, hot flush. Central Nervous System : Facial dyskinesia, insomnia, migraine, increased intracranial pressure, seizure, tremor. Dermatologic : Flushing, hyperhidrosis, pruritus, rash. Endocrine/Metabolic : Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Cases of androgen deficiency have occurred with chronic use of opioids. Gastrointestinal : Abdominal pain, bowel obstruction, decreased appetite, diarrhea, difficulty swallowing, dry mouth, GERD, indigestion, pancreatitis, paralytic ileus, biliary tract spasm (spasm of the sphincter of Oddi). Genitourinary : Urinary tract infection, ureteral spasm, spasm of vesicle sphincters, urinary retention. Laboratory : Increases in serum amylase. Musculoskeletal : Arthralgia, backache, muscle spasm. Ophthalmic : Miosis (constricted pupils), visual disturbances. Psychiatric : Agitation, anxiety, confusion, fear, dysphoria, depression. Reproductive : Hypogonadism, infertility. Respiratory : Bronchitis, cough, dyspnea, nasal congestion, nasopharyngitis, respiratory depression, sinusitis, upper respiratory tract infection. Other : Drug abuse, drug dependence, opioid withdrawal syndrome. Common adverse reactions include: Sedation (somnolence, mental clouding, lethargy), impaired mental and physical performance, lightheadedness, dizziness, headache, dry mouth, nausea, vomiting, and constipation. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Lupin Pharmaceuticals, Inc. at 866-403-7592 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.