Drug Safety-related Labeling Changes (SrLC)
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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
HYCODAN (NDA-005213)
(HOMATROPINE METHYLBROMIDE; HYDROCODONE BITARTRATE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
12/15/2023 (SUPPL-46)
09/27/2021 (SUPPL-44)
06/28/2018 (SUPPL-39)
Boxed Warning
(section updated)
WARNING: ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; MEDICATION ERRORS; CYTOCHROME P450 3A4 INTERACTION; CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS; INTERACTION WITH ALCOHOL; NEONATAL OPIOID WITHDRAWAL SYNDROME
HYCODAN exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Reserve HYCODAN 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. Assess each patient’s risk prior to prescribing HYCODAN, prescribe HYCODAN for the shortest duration that is consistent with individual patient treatment goals, monitor all patients regularly for the development of addition or abuse, and refill only after reevaluation of the need for continued treatment.
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory depression may occur with use of HYCODAN. Monitor for respiratory depression, especially during initiation of HYCODAN therapy or when used in patients at higher risk.
Accidental ingestion of even one dose of HYCODAN, especially by children, can result in a fatal overdose of hydrocodone.
Ensure accuracy when prescribing, dispensing, and administering HYCODAN. Dosing errors can result in accidental overdose and death. Always use an accurate milliliter measuring device when measuring and administering HYCODAN.
Cytochrome P450 3A4 Interaction
The concomitant use of HYCODAN with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in hydrocodone plasma concentration. Avoid the use of HYCODAN in patients taking a CYP3A4 inhibitor or inducer.
4 Contraindications
(additions
underlined)
HYCODAN is contraindicated for:
All children younger than 6 years of age
HYCODAN
is also contraindicated in patients with:
Significant respiratory depression
Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
Known or suspected gastrointestinal obstruction, including paralytic ileus
Hypersensitivity to hydrocodone, homatropine, or any of the inactive ingredients in HYCODAN
5 Warnings and Precautions
(PLR conversion: subsections created as below, see label for complete information)
5.1 Addiction, Abuse, and Misuse
5.2 Life-Threatening Respiratory Depression
5.3 Risks with Use in Pediatric Populations
5.4 Risks with Use in Other At-Risk Populations
5.5 Risk of Accidental Overdose and Death due to Medication Errors
5.6 Activities Requiring Mental Alertness: Risks of Driving and Operating Machinery
5.7 Risks from Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers
5.8 Risks from Concomitant Use with Benzodiazepines or other CNS Depressants
5.9 Risks of Use in Patients with Gastrointestinal Conditions
5.10 Risks of Use in Patients with Head Injury, Impaired Consciousness, Increased Intracranial Pressure, or Brain Tumors
5.11 Increased Risk of Seizures in Patients with Seizure Disorders
5.12 Severe Hypotension
5.13 Neonatal Opioid Withdrawal Syndrome
5.14 Adrenal Insufficiency
5.15 Drug/Laboratory Test Interactions
6 Adverse Reactions
(additions underlined)
The following serious adverse reactions are described, or described in greater detail, in other sections:
Addiction, abuse, and misuse
Life-threatening respiratory depression
Accidental overdose and death due to medication errors
Decreased mental alertness with impaired mental and/or physical abilities
Interactions with benzodiazepines and other CNS depressants
Paralytic ileus, gastrointestinal adverse reactions
Increased intracranial pressure
Obscured clinical course in patients with head injuries
Seizures
Severe hypotension
Neonatal Opioid Withdrawal Syndrome
Adrenal insufficiency
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 HYCODAN 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 HYCODAN.
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.
7 Drug Interactions
(extensive additions, please refer to label)
8 Use in Specific Populations
8.1 Pregnancy(PLLR conversion, please refer to label)
(PLLR conversion)
Risk Summary
Because of the potential for serious adverse reactions, including excess sedation, respiratory depression, and death in a breastfed infant, advise patients that breastfeeding is not recommended during treatment with HYCODAN.
There are no data on the presence of HYCODAN in human milk, the effects of HYCODAN on the breastfed infant, or the effects of HYCODAN on milk production; however, data are available with hydrocodone and homatropine.
Hydrocodone
Hydrocodone is present in breast milk. Published cases report variable concentrations of hydrocodone and hydromorphone (an active metabolite) in breast milk with administration of immediate-release hydrocodone to nursing mothers in the early post-partum period with relative infant doses of hydrocodone ranging between 1.4 and 3.7%. There are case reports of excessive sedation and respiratory depression in breastfed infants exposed to hydrocodone. No information is available on the effects of hydrocodone on milk production.
Homatropine
No information is available on the levels of homatropine in breast milk or on milk production. The published literature suggests that homatropine may decrease milk production based on its anticholinergic effects (see Clinical Considerations).
Infants exposed to HYCODAN through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid is stopped, or when breastfeeding is stopped.
(PLLR conversion)
Infertility
Chronic use of opioids, such as hydrocodone, a component of HYCODAN, may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible.
(subsection revised, additions underlined)
HYCODAN is not indicated for use in patients younger than 18 years of age because the benefits of symptomatic treatment of cough associated with allergies or the common cold do not outweigh the risks for use of hydrocodone in these patients.
Life-threatening respiratory depression and death have occurred in children who received hydrocodone. Because of the risk of life-threatening respiratory depression and death, HYCODAN is contraindicated in children less than 6 years of age.
(new subsection added)
Clinical studies have not been conducted with HYCODAN in geriatric populations.
Use caution when considering the use of HYCODAN in patients 65 years of age or older. Elderly patients may have increased sensitivity to hydrocodone; greater frequency of decreased hepatic, renal, or cardiac function; or concomitant disease or other drug therapy.
Respiratory depression is the chief risk for elderly patients treated with opioids, including HYCODAN. Respiratory depression has occurred after large initial doses of opioids were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration.
Hydrocodone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, monitor these patients closely for respiratory depression, sedation, and hypotension.
(new subsection added)
The pharmacokinetics of HYCODAN has not been characterized in patients with renal impairment. Patients with renal impairment may have higher plasma concentrations than those with normal function. HYCODAN should be used with caution in patients with severe impairment of renal function, and patients should be monitored closely for respiratory depression, sedation, and hypotension.
(new subsection added)
The pharmacokinetics of HYCODAN has not been characterized in patients with hepatic impairment. Patients with severe hepatic impairment may have higher plasma concentrations than those with normal hepatic function. Therefore, HYCODAN should be used with caution in patients with severe impairment of hepatic function, and patients should be monitored closely for respiratory depression, sedation, and hypotension.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE(additions and revisions, please refer to label)
(new section added; please refer to label)
Other
(PLR conversion)