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.
TUSSIONEX PENNKINETIC (NDA-019111)
(CHLORPHENIRAMINE POLISTIREX; HYDROCODONE POLISTIREX)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
06/28/2018 (SUPPL-22)
Boxed Warning
(extensive additions, please refer to label)
4 Contraindications
(additions underlined)
All children younger than 6 years of age.
TUSSIONEX Pennkinetic 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, chlorpheniramine, or any of the inactive ingredients in TUSSIONEX Pennkinetic.
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 of Use in Pediatric Populations
5.4 Risks of 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
(revisions and additions, please refer to label)
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 TUSSIONEX Pennkinetic.
There are no data on the presence of TUSSIONEX Pennkinetic in human milk, the effects of TUSSIONEX Pennkinetic on the breastfed infant, or the effects of TUSSIONEX Pennkinetic on milk production; however, data are available with hydrocodone and chlorpheniramine.
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.
Chlorpheniramine
Chlorpheniramine is present in human milk. Chlorpheniramine has not been reported to cause effects on the breastfed infant. The published literature suggests that chlorpheniramine may decrease milk production based on its anticholinergic effects. (see Clinical Considerations)
Clinical Considerations
Infants exposed to TUSSIONEX Pennkinetic 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 TUSSIONEX Pennkinetic, may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible.
(additions underlined)
TUSSIONEX Pennkinetic 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, TUSSIONEX Pennkinetic is contraindicated in children less than 6 years of age.
(additions underlined)
Clinical studies have not been conducted with TUSSIONEX Pennkinetic in geriatric populations.
Use caution when considering the use of TUSSIONEX Pennkinetic 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 TUSSIONEX Pennkinetic. 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 TUSSIONEX Pennkinetic has not been characterized in patients with renal impairment. Patients with renal impairment may have higher plasma concentrations than those with normal function. Chlorpheniramine is cleared substantially by the kidney. As such, impaired renal function could potentially lead to the risk of decreased clearance and thereby increased retention or systemic levels of chlorpheniramine. Therefore, TUSSIONEX Pennkinetic should be used with caution in patients with severe impairment of renal function, and patients should be monitored closely for signs of hydrocodone toxicity (respiratory depression, sedation, and hypotension) and chlorpheniramine toxicity.
(new subsection added)
The pharmacokinetics of TUSSIONEX Pennkinetic 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. Chlorpheniramine is extensively metabolized by liver before elimination from the body. As such, impaired hepatic function could potentially lead to the risk of decreased metabolism and thereby increased systemic levels of chlorpheniramine. Therefore, TUSSIONEX Pennkinetic should be used with caution in patients with severe impairment of hepatic function, and patients should be monitored closely for signs of hydrocodone toxicity (respiratory depression, sedation, and hypotension) and chlorpheniramine toxicity.
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)