Approved Drug Label (PDF)
Boxed Warning
(extensive
additions, please refer to label)
4
Contraindications
(additions
underlined)
HYCOFENIX is contraindicated for:
HYCOFENIX
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.
Narrow angle glaucoma, urinary retention,
severe hypertension, or severe coronary artery disease.
Hypersensitivity to hydrocodone, pseudoephedrine,
guaifenesin, or any of the inactive ingredients in HYCOFENIX.
5
Warnings and Precautions
5.10 Risks of Use in Patients with Head Injury, Impaired Consciousness, Increased Intracranial Pressure, or Brain Tumors
(additions underlined)
Avoid the use of HYCOFENIX in patients with
head injury, intracranial lesions, or a pre-existing increase in intracranial
pressure. In patients who may be
susceptible to the intracranial effects of CO2 retention (e.g., those with
evidence of increased intracranial pressure or brain tumors), HYCOFENIX may
reduce respiratory drive, and the resultant CO2 retention can further increase
intracranial pressure.
Furthermore, opioids produce adverse reactions that may obscure the
clinical course of patients with head injuries.
5.11 Cardiovascular and Central Nervous System Effects
(additions
underlined)
The
pseudoephedrine contained in HYCOFENIX can produce cardiovascular and central
nervous system effects in some patients such as, insomnia, dizziness, weakness,
tremor, transient elevations in blood pressure, or arrhythmias. In addition, central nervous system
stimulation with convulsions or cardiovascular collapse with accompanying
hypotension has been reported. Therefore, HYCOFENIX is contraindicated in
patients with severe hypertension or coronary artery disease , and should,
be used with caution in patients with other cardiovascular disorders.
5.8 Risks from Concomitant Use with Benzodiazepines or other CNS Depressants
(additions
underlined)
…
Patients must not consume alcoholic
beverages, or prescription or non-prescription products containing alcohol, while
on HYCOFENIX therapy. The co-ingestion of alcohol with HYCOFENIX may result in
increased plasma levels and a potentially fatal overdose of hydrocodone.
5.9 Risks of Use in Patients with Gastrointestinal Conditions
(additions
underlined)
HYCOFENIX is contraindicated in patients with
known or suspected gastrointestinal obstruction, including paralytic ileus.The
use of hydrocodone in HYCOFENIX may obscure the diagnosis
or clinical course of patients with acute abdominal conditions.
The concurrent use of anticholinergics with HYCOFENIX may
produce paralytic ileus.
The
hydrocodone in HYCOFENIX may result in constipation or obstructive bowel
disease, especially in patients with underlying intestinal motility disorders.
Use with caution in patients with underlying intestinal motility disorders.
The hydrocodone in HYCOFENIX may cause spasm of the
sphincter of Oddi, resulting in an increase in biliary tract pressure. Opioids
may cause increases in serum amylase. Monitor patients with biliary tract
disease, including acute pancreatitis for worsening symptoms.
(The
following new subsections have been added, please refer to label for more
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
5.7 Risks from Concomitant Use or Discontinuation
of Cytochrome P450 3A4 Inhibitors and Inducers
5.12 Increased Risk of Seizures in Patients with
Seizure Disorders
5.13 Severe Hypotension
5.14 Neonatal Opioid Withdrawal Syndrome
5.15 Adrenal Insufficiency
5.16 Drug/Laboratory Test Interactions
6
Adverse Reactions
(extensive
additions, please refer to label)
7
Drug Interactions
7.1 Alcohol
(new
subsection added)
Concomitant use of alcohol with HYCOFENIX can result in
an increase of hydrocodone plasma levels and potentially fatal overdose of
hydrocodone. Instruct patients not to
consume alcoholic beverages or use prescription or nonprescription products
containing alcohol while on HYCOFENIX therapy.
7.10 Antihypertensive drugs
(new
subsection added)
Due to the antagonistic pharmacologic effects of
pseudoephedrine, one of the active ingredients in HYCOFENIX, the concomitant
use of HYCOFENIX with antihypertensive drugs which interfere with sympathetic
activity (e.g., methyldopa, mecamylamine, and reserpine) may reduce their
antihypertensive effects. Use HYCOFENIX
with caution in patients who are taking antihypertensive drugs.
7.11 Digitalis
(new
subsection added)
Increased ectopic pacemaker activity can occur when
pseudoephedrine is used concomitantly with digitalis. Use HYCOFENIX with
caution in patients who are taking digitalis.
7.2 Inhibitors of CYP3A4 and CYP2D6
(new subsection added)
The concomitant use of HYCOFENIX and CYP3A4 inhibitors,
such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents
(e.g. ketoconazole), or protease inhibitors (e.g., ritonavir), can increase the
plasma concentration of hydrocodone, resulting in increased or prolonged opioid
effects. These effects could be more pronounced with concomitant use of
HYCOFENIX and CYP2D6 and CYP3A4 inhibitors, particularly when an inhibitor is
added after a stable dose of HYCOFENIX is achieved. After stopping a CYP3A4
inhibitor, as the effects of the inhibitor decline, the hydrocodone plasma
concentration will decrease, resulting in decreased opioid efficacy or a
withdrawal syndrome in patients who had developed physical dependence to
hydrocodone.
Avoid the use of HYCOFENIX while taking a CYP3A4 or
CYP2D6 inhibitor. If concomitant use is
necessary, monitor patients for respiratory depression and sedation at frequent
intervals.
7.3 CYP3A4 Inducers
(new subsection added)
The concomitant use of HYCOFENIX and CYP3A4 inducers such
as rifampin, carbamazepine, or phenytoin, can decrease the plasma concentration
of hydrocodone, resulting in decreased efficacy or onset of a withdrawal
syndrome in patients who have developed physical dependence to hydrocodone.
After stopping a CYP3A4 inducer, as the effects of the inducer decline, the
hydrocodone plasma concentration will increase, which could increase or prolong
both the therapeutic effects and adverse reactions, and may cause serious respiratory
depression.
Avoid the use of HYCOFENIX in patients who are taking
CYP3A4 inducers. If concomitant use of a
CYP3A4 inducer is necessary, follow the patient for reduced efficacy.
7.4 Benzodiazepines, and Other CNS Depressants
(subsection
revised, additions underlined)
Due to additive pharmacologic effect, the concomitant use
of benzodiazepines or other CNS depressants, including alcohol, other
sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general
anesthetics, antipsychotics, and other opioids, can increase the risk of
hypotension, respiratory depression, profound sedation, coma, and death. Avoid the use of HYCOFENIX in patients who are
taking benzodiazepines or other CNS depressants, and instruct patients to avoid
consumption of alcohol while on HYCOFENIX.
7.5 Serotonergic Drugs
(new
subsection added)
The concomitant use of opioids with other drugs that
affect the serotonergic neurotransmitter system has resulted in serotonin
syndrome. If concomitant use is
warranted, carefully observe the patient, particularly during treatment
initiation. Discontinue HYCOFENIX if serotonin syndrome is suspected.
7.6 Monoamine Oxidase Inhibitors (MAOIs)
(additions
underlined)
Avoid the use of HYCOFENIX in patients who
are taking monoamine oxidase inhibitors (MAOIs) or have taken MAOIs within 14
days. The use of MAOIs or tricyclic antidepressants with
hydrocodone, one of the active ingredients in HYCOFENIX, may increase
the effect of either the antidepressant or hydrocodone. MAOI interactions
with opioids may manifest as serotonin syndrome or opioid toxicity
(e.g., respiratory depression, coma). An
increase in blood pressure or hypertensive crisis may also occur when
pseudoephedrine containing preparations are used with MAOIs.
7.7 Muscle Relaxants
(new
subsection added)
Hydrocodone may enhance the neuromuscular blocking action
of skeletal muscle relaxants and produce an increased degree of respiratory
depression. Avoid the use of HYCOFENIX
in patients taking muscle relaxants. If concomitant use is necessary, monitor
patients for signs of respiratory depression that may be greater than otherwise
expected.
7.8 Diuretics
(new
subsection added)
Opioids can reduce the efficacy of diuretics by inducing
the release of antidiuretic hormone. Monitor patients for signs of diminished
diuresis and/or effects on blood pressure and increase the dosage of the
diuretic as needed.
7.9 Anticholinergic Drugs
(additions
underlined)
The concomitant use of anticholinergic
drugs with HYCOFENIX may increase risk of urinary retention and/or severe
constipation, which may lead to paralytic ileus. Monitor patients for
signs of urinary retention or reduced gastric motility when HYCOFENIX is used
concomitantly with anticholinergic drugs.
8
Use in Specific Populations
8.1 Pregnancy
(PLLR
conversion, please refer to label)
8.2 Lactation
(PLLR conversion, please
refer to label)
8.3 Females and Males of Reproductive Potential
(PLLR
conversion)
Infertility
Chronic use of opioids, such as hydrocodone, a component
of HYCOFENIX, may cause reduced fertility in females and males of reproductive
potential. It is not known whether these effects on fertility are reversible.
8.4 Pediatric Use
(additions
underlined)
SafetyHYCOFENIX 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, HYCOFENIX is contraindicated in
children less than 6 years of age.
8.5 Geriatric Use
(additions
underlined)
Clinical studies have not been conducted with HYCOFENIX
in geriatric populations.
Use caution when considering the use of
HYCOFENIX 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 HYCOFENIX. 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.
8.6 Renal Impairment
(additions underlined)
The pharmacokinetics of HYCOFENIX has not been
characterized in patients with renal impairment. Patients with renal
impairment may have higher plasma concentrations than those with normal
function.
Pseudoephedrine is primarily excreted unchanged in the
urine. Therefore, pseudoephedrine may
accumulate in patients with renal impairment. HYCOFENIX 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 pseudoephedrine toxicity.
8.7 Hepatic Impairment
(additions
underlined)
The pharmacokinetics of HYCOFENIX 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, HYCOFENIX 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)
PATIENT COUNSELING INFORMATION
(extensive
additions, please refer to label)
Approved Drug Label (PDF)
Boxed Warning
(section
added)
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.
Avoid use of opioid cough medications in patients taking benzodiazepines, other
CNS depressants, or alcohol.
5
Warnings and Precautions
5.1 Risks from Concomitant Use with Benzodiazepines or other CNS Depressants
(subsection
added)
Concomitant use of opioids, including HYCOFENIX,
with benzodiazepines, or other CNS depressants, including alcohol, may result
in profound sedation, respiratory depression, coma, and death. Because of these
risks, avoid use of opioid cough medications in patients taking benzodiazepines,
other CNS depressants, or alcohol.
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 HYCOFENIX
is used with benzodiazepines, alcohol, or other CNS depressants.
7
Drug Interactions
7.1 Benzodiazepines, Opioids, Antihistamines, Antipsychotics, Anti-anxiety Agents, or Other CNS Depressants (Including Alcohol)
(subsection
revised, additions underlined)
The use of benzodiazepines,
opioids, antihistamines, antipsychotics, anti-anxiety agents, or other CNS
depressants (including alcohol) concomitantly with HYCOFENIX may cause
an additive CNS depressant effect, profound sedation, respiratory depression,
coma, and death and should be avoided.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(additions
underlined)
…
Interactions with Benzodiazepines and Other
Central Nervous System Depressants
Inform patients and caregivers that potentially fatal
additive effects may occur if HYCOFENIX is used with benzodiazepines or other
CNS depressants, including alcohol. Because of this risk, patients
should avoid concomitant use of HYCOFENIX with benzodiazepines or other CNS
depressants, including alcohol.
…
MAOIs
Patients should be informed
that due to its pseudoephedrine component, they should not use HYCOFENIX with
an MAOI or within 14 days of stopping use of an MAOI.
MEDICATION GUIDE
(New
section added, please refer to label)