Included as part of the PRECAUTIONS section.
Addiction, Abuse, And Misuse
HYSINGLA ER contains hydrocodone, a Schedule II
controlled substance. As an opioid, HYSINGLA ER exposes users to the risks of
addiction, abuse, and misuse. Because extended-release products such as
HYSINGLA ER deliver the opioid over an extended period of time, there is a
greater risk for overdose and death due to the larger amount of hydrocodone present
[see Drug Abuse and Dependence].
Although the risk of addiction in any individual is
unknown, it can occur in patients appropriately prescribed HYSINGLA ER.
Addiction can occur at recommended doses and if the drug is misused or abused.
Assess each patient's risk for opioid addiction, abuse,
or misuse prior to prescribing HYSINGLA ER, and monitor all patients receiving
HYSINGLA ER for the development of these behaviors and conditions. Risks are
increased in patients with a personal or family history of substance abuse
(including drug or alcohol addiction or abuse) or mental illness (e.g., major
depression). The potential for these risks should not, however, prevent the
prescribing of HYSINGLA ER for the proper management of pain in any given
patient. Patients at increased risk may be prescribed opioids such as HYSINGLA
ER, but use in such patients necessitates intensive counseling about the risks
and proper use of HYSINGLA ER along with intensive monitoring for signs of
addiction, abuse, and misuse.
Abuse or misuse of HYSINGLA ER by crushing, chewing,
snorting, or injecting the dissolved product will result in the uncontrolled
delivery of the hydrocodone and can result in overdose and death [see Drug
Abuse and Dependence, OVERDOSAGE].
Opioids are sought by drug abusers and people with
addiction disorders and are subject to criminal diversion. Consider these risks
when prescribing or dispensing HYSINGLA ER. Strategies to reduce these risks
include prescribing the drug in the smallest appropriate quantity and advising
the patient on the proper disposal of unused drug [see PATIENT INFORMATION]. Contact local state professional licensing board or state
controlled substances authority for information on how to prevent and detect
abuse or diversion of this product.
Life-Threatening Respiratory Depression
Serious, life-threatening, or fatal respiratory
depression has been reported with the use of opioids, even when used as
recommended. Respiratory depression, if not immediately recognized and treated,
may lead to respiratory arrest and death. Management of respiratory depression
may include close observation, supportive measures, and use of opioid
antagonists, depending on the patient's clinical status [see OVERDOSAGE].
Carbon dioxide (CO2) retention from opioid-induced respiratory depression can
exacerbate the sedating effects of opioids.
While serious, life-threatening, or fatal respiratory
depression can occur at any time during the use of HYSINGLA ER, the risk is
greatest during the initiation of therapy or following a dosage increase.
Monitor patients closely for respiratory depression especially within the first
24-72 hours of initiating therapy with and following dosage increases of
To reduce the risk of respiratory depression, proper
dosing and titration of HYSINGLA ER are essential [see DOSAGE AND
ADMINISTRATION]. Overestimating the HYSINGLA ER dosage when converting
patients from another opioid product can result in fatal overdose with the
Accidental ingestion of even one dose of HYSINGLA ER,
especially by children, can result in respiratory depression and death due to
an overdose of hydrocodone.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of HYSINGLA ER during pregnancy can result
in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike
opioid withdrawal syndrome in adults, may be life-threatening if not recognized
and treated, and requires management according to protocols developed by
neonatology experts. Observe newborns for signs of neonatal opioid withdrawal
syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged
period of the risk of neonatal opioid withdrawal syndrome and ensure that
appropriate treatment will be available [see Use in Specific Populations,
Risks Of Concomitant Use Or Discontinuation Of Cytochrome
P450 3A4 Inhibitors And Inducers
Concomitant use of HYSINGLA ER with a CYP3A4 inhibitor,
such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents
(e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase
plasma concentrations of hydrocodone and prolong opioid adverse reactions,
which may cause potentially fatal respiratory depression [see Life-Threatening Respiratory Depression], particularly when an inhibitor is added after a stable dose
of HYSINGLA ER is achieved. Similarly, discontinuation of a CYP3A4 inducer,
such as rifampin, carbamazepine, and phenytoin, in HYSINGLA ER treated patients
may increase hydrocodone plasma concentrations and prolong opioid adverse
reactions. When using HYSINGLA ER with CYP3A4 inhibitors or discontinuing
CYP3A4 inducers in HYSINGLA ER treated patients, monitor patients closely at
frequent intervals and consider dosage reduction of HYSINGLA ER until stable
drug effects are achieved [see DRUG INTERACTIONS].
Concomitant use of HYSINGLA ER with CYP3A4 inducers or
discontinuation of an CYP3A4 inhibitor could decrease hydrocodone plasma
concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal
syndrome in a patient who had developed physical dependence to hydrocodone.
When using HYSINGLA ER with CYP3A4 inducers or discontinuing CYP3A4 inhibitors,
monitor patients closely at frequent intervals and consider increasing the
opioid dosage if needed to maintain adequate analgesia or if symptoms of opioid
withdrawal occur [see DRUG INTERACTIONS].
Risks From Concomitant Use With Benzodiazepines Or Other
Profound sedation, respiratory depression, coma, and
death may result from the concomitant use of HYSINGLA ER with benzodiazepines
or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics,
anxiolytics, tranquilizers, muscle relaxants, general anesthetics,
antipsychotics, other opioids, alcohol). Because of these risks, reserve
concomitant prescribing of these drugs for use in patients for whom alternative
treatment options are inadequate.
Observational studies have demonstrated that concomitant
use of opioid analgesics and benzodiazepines increases the risk of drug-related
mortality compared to use of opioid analgesics alone. Because of similar
pharmacological properties, it is reasonable to expect similar risk with the
concomitant use of other CNS depressant drugs with opioid analgesics [see DRUG
If the decision is made to prescribe a benzodiazepine or
other CNS depressant concomitantly with an opioid analgesic, prescribe the
lowest effective dosages and minimum durations of concomitant use. In patients
already receiving an opioid analgesic, prescribe a lower initial dose of the
benzodiazepine or other CNS depressant than indicated in the absence of an
opioid, and titrate based on clinical response. If an opioid analgesic is
initiated in a patient already taking a benzodiazepine or other CNS depressant,
prescribe a lower initial dose of the opioid analgesic, and titrate based on
clinical response. Follow patients closely for signs and symptoms of
respiratory depression and sedation.
Advise both patients and caregivers about the risks of
respiratory depression and sedation when HYSINGLA ER is used with
benzodiazepines or other CNS depressants (including alcohol and illicit drugs).
Advise patients not to drive or operate heavy machinery until the effects of
concomitant use of the benzodiazepine or other CNS depressant have been
determined. Screen patients for risk of substance use disorders, including
opioid abuse and misuse, and warn them of the risk for overdose and death
associated with the use of additional CNS depressants including alcohol and illicit
drugs [see DRUG INTERACTIONS, PATIENT INFORMATION].
Life-Threatening Respiratory Depression In Patients With Chronic
Pulmonary Disease Or In Elderly, Cachectic, Or Debilitated Patients
The use of HYSINGLA ER in patients with acute or severe
bronchial asthma in an unmonitored setting or in the absence of resuscitative
equipment is contraindicated.
Patients With Chronic Pulmonary Disease
HYSINGLA ER-treated patients with significant chronic
obstructive pulmonary disease or cor pulmonale, and those with a substantially
decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing
respiratory depression are at increased risk of decreased respiratory drive
including apnea, even at recommended dosages of HYSINGLA ER[see Life-Threatening Respiratory Depression].
Elderly, Cachectic, Or Debilitated Patients
Life-threatening respiratory depression is more likely to
occur in elderly, cachectic, or debilitated patients because they may have
altered pharmacokinetics or altered clearance compared to younger, healthier
patients [see Life-Threatening Respiratory Depression].
Monitor such patients closely, particularly when
initiating and titrating HYSINGLA ER and when HYSOINGLA ER is given
concomitantly with other drugs that depress respiration [see Life-Threatening Respiratory Depression and Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants]. Alternatively, consider the use of non-opioid analgesics in
Cases of adrenal insufficiency have been reported with
opioid use, more often following greater than one month of use. Presentation of
adrenal insufficiency may include non-specific symptoms and signs including
nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood
pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic
testing as soon as possible. If adrenal insufficiency is diagnosed, treat with
physiologic replacement doses of corticosteroids. Wean the patient off of the
opioid to allow adrenal function to recover and continue corticosteroid
treatment until adrenal function recovers. Other opioids may be tried as some
cases reported use of a different opioid without recurrence of adrenal
insufficiency. The information available does not identify any particular
opioids as being more likely to be associated with adrenal insufficiency.
HYSINGLA ER may cause severe hypotension including
orthostatic hypotension and syncope in ambulatory patients. There is an
increased risk in patients whose ability to maintain blood pressure has already
been compromised by a reduced blood volume, or after concurrent administration
of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see
DRUG INTERACTIONS]. Monitor these patients for signs of hypotension
after initiating or titrating the dosage of HYSINGLA ER. In patients with
circulatory shock, HYSINGLA ER may cause vasodilation that can further reduce
cardiac output and blood pressure. Avoid the use of HYSINGLA ER in patients
with circulatory shock.
QTc Interval Prolongation
QTc prolongation has been observed with HYSINGLA ER
following daily doses of 160 mg [see CLINICAL PHARMACOLOGY]. This
observation should be considered in making clinical decisions regarding patient
monitoring when prescribing HYSINGLA ER in patients with congestive heart
failure, bradyarrhythmias, electrolyte abnormalities, or who are taking
medications that are known to prolong the QTc interval.
HYSINGLA ER should be avoided in patients with congenital
long QT syndrome. In patients who develop QTc prolongation, consider reducing
the dose by 33 - 50%, or changing to an alternate analgesic.
Risks Of Use In Patients With Increased Intracranial
Pressure, Brain Tumors, Head Injury, Or Impaired Consciousness
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), HYSINGLA ER may reduce respiratory drive, and the
resultant CO2 retention can further increase intracranial pressure. Monitor
such patients for signs of sedation and respiratory depression, particularly
when initiating therapy with HYSINGLA ER.
Opioids may also obscure the clinical course in a patient
with a head injury. Avoid the use of HYSINGLA ER in patients with impaired
consciousness or coma.
Gastrointestinal Obstruction, Dysphagia, And Choking
In the clinical studies with specific instructions to
take HYSINGLA ER with adequate water to swallow the tablet, 11 out of 2476
subjects reported difficulty swallowing HYSINGLA ER. These reports included
esophageal obstruction, dysphagia, and choking, one of which had required
medical intervention to remove the tablet [see ADVERSE REACTIONS].
Instruct patients not to pre-soak, lick, or otherwise wet
HYSINGLA ER tablets prior to placing in the mouth, and to take one tablet at a
time with enough water to ensure complete swallowing immediately after placing
in the mouth [see PATIENT INFORMATION].
Patients with underlying gastrointestinal disorders such
as esophageal cancer or colon cancer with a small gastrointestinal lumen are at
greater risk of developing these complications. Consider use of an alternative
analgesic in patients who have difficulty swallowing and patients at risk for
underlying gastrointestinal disorders resulting in a small gastrointestinal
Pediatric patients may be at increased risk of esophageal
obstruction, dysphagia, and choking because of a smaller gastrointestinal lumen
if they ingest HYSINGLA ER [see Use in Specific Populations].
Risks Of Use In Patients With Gastrointestinal Conditions
HYSINGLA ER is contraindicated in patients with known or
suspected gastrointestinal obstruction, including paralytic ileus.
The hydrocodone in HYSINGLA ER may cause spasm of the
sphincter of Oddi. Opioids may cause increases in serum amylase. Monitor
patients with biliary tract disease, including acute pancreatitis, for
Increased Risk Of Seizures In Patients With Seizure
The hydrocodone in HYSINGLA ER may increase the frequency
of seizures in patients with seizure disorders, and may increase the risk of
seizures occurring in other clinical settings associated with seizures. Monitor
patients with a history of seizure disorders for worsened seizure control
during HYSINGLA ER therapy.
Avoid the use of mixed agonist/antagonist analgesics
(e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g.,
buprenorphine) analgesics in patients who are receiving a full opioid agonist
analgesic, including HYSINGLA ER. In these patients, mixed agonist/antagonist
and partial agonist analgesics may reduce the analgesic effect and/or may
precipitate withdrawal symptoms [see DRUG INTERACTIONS].
When discontinuing HYSINGLA ER, gradually taper the
dosage [see DOSAGE AND ADMINISTRATION]. Do not abruptly discontinue
HYSINGLA ER [see Drug Abuse and Dependence].
Risks Of Driving And Operating Machinery
HYSINGLA ER may impair the mental and physical abilities
needed to perform potentially hazardous activities such as driving a car or
operating machinery. Peak blood levels of hydrocodone may occur 14 - 16 hours
(range 6 - 30 hours) after initial dosing of HYSINGLA ER tablet administration.
Blood levels of hydrocodone, in some patients, may be high at the end of 24
hours after repeated-dose administration. Warn patients not to drive or operate
dangerous machinery unless they are tolerant to the effects of HYSINGLA ER and
know how they will react to the medication [see CLINICAL PHARMACOLOGY, PATIENT INFORMATION].
Patient Counseling Information
Advise the patient to read the
FDA-approved patient labeling (Medication Guide)
Addiction, Abuse, And Misuse
Inform patients that the use of
HYSINGLA ER, even when taken as recommended, can result in addiction, abuse,
and misuse, which can lead to overdose or death [see WARNINGS AND
Instruct patients not to share HYSINGLA ER with others and to take steps to
protect HYSINGLA ER from theft or misuse.
Inform patients of the risk of
life-threatening respiratory depression, including information that the risk is
greatest when starting HYSINGLA ER or when the dosage is increased, and that it
can occur even at recommended dosages [see WARNINGS AND PRECAUTIONS]. Advise patients how to
recognize respiratory depression and to seek medical attention if breathing
Inform patients that accidental ingestion, especially by
children, may result in respiratory depression or death [see WARNINGS AND
PRECAUTIONS]. Instruct patients to take steps to store HYSINGLA ER securely
and to dispose of unused HYSINGLA ER by flushing the tablets down the toilet.
Interaction With Benzodiazepines And Other CNS
Inform patients and caregivers that potentially fatal
additive effects may occur if HYSINGLA ER is used with benzodiazepines or other
CNS depressants, including alcohol, and not to use these concomitantly unless
supervised by a health care provider [see WARNINGS AND PRECAUTIONS, DRUG
Inform patients that opioids could cause a rare but
potentially life-threatening condition resulting from concomitant
administration of serotonergic drugs. Warn patients of the symptoms of
serotonin syndrome and to seek medical attention right away if symptoms
develop. Instruct patients to inform their healthcare providers if they are
taking, or plan to take serotonergic medications[see DRUG INTERACTIONS].
Inform patients to avoid taking HYSINGLA ER while using
any drugs that inhibit monoamine oxidase. Patients should not start MAOIs while
taking HYSINGLA ER [see DRUG INTERACTIONS].
Inform patients that opioids could cause adrenal
insufficiency, a potentially life-threatening condition. Adrenal insufficiency
may present with non-specific symptoms and signs such as nausea, vomiting,
anorexia, fatigue, weakness, dizziness, and low blood pressure. Advise patients
to seek medical attention if they experience a constellation of these symptoms [see
WARNINGS AND PRECAUTIONS].
Important Administration Instructions
Instruct patients how to properly take HYSINGLA ER,
including the following:
- Use HYSINGLA ER exactly as prescribed to reduce the risk
of life-threatening adverse reactions (e.g., respiratory depression) [see WARNINGS
- Swallow tablets whole, one tablet at a time, with enough
water to ensure swallowing immediately after placing in the mouth [see
DOSAGE AND ADMINISTRATION].
- Do not pre-soak, lick, or otherwise wet the tablet prior
to placing in the mouth [see DOSAGE AND ADMINISTRATION]
- Do not chew, crush, or dissolve the tablets [see DOSAGE
- Do not discontinue HYSINGLA ER without first discussing
the need for a tapering regimen with the prescriber [see DOSAGE AND
Inform patients that HYSINGLA ER may cause orthostatic
hypotension and syncope. Instruct patients how to recognize symptoms of low
blood pressure and how to reduce the risk of serious consequences should
hypotension occur (e.g., sit or lie down, carefully rise from a sitting or
lying position) [see WARNINGS AND PRECAUTIONS].
QT Interval Prolongation
Inform patients that QT prolongation has been observed
with HYSINGLA ER [see CLINICAL PHARMACOLOGY]. HYSINGLA ER should be
avoided in patients with congenital long QT syndrome. Instruct patients with a
history of congestive heart failure or bradyarrhythmias, and patients at risk
for electrolyte abnormalities or who are taking other medications known to
prolong the QT interval, that periodic monitoring of electrocardiograms and
electrolytes may be necessary during therapy with HYSINGLA ER [see WARNINGS
Inform patients that anaphylaxis has been reported with
ingredients contained in HYSINGLA ER. Advise patients how to recognize such a
reaction and when to seek medical attention [see CONTRAINDICATION, ADVERSE
Neonatal Opioid Withdrawal Syndrome
Inform female patients of reproductive potential that
prolonged use of HYSINGLA ER during pregnancy can result in neonatal opioid
withdrawal syndrome, which may be life-threatening if not recognized and
treated [see WARNINGS AND PRECAUTIONS, Use in Specific Populations].
Inform female patients of reproductive potential that
HYSINGLA ER can cause fetal harm and to inform their healthcare provider of a
known or suspected pregnancy [see Use in Specific Populations].
Advise patients that breastfeeding is not recommended
during treatment with HYSINGLA ER [see Use in Specific Populations]
Inform patients that chronic use of opioids may cause
reduced fertility. It is not known whether these effects on fertility are
reversible [see ADVERSE REACTIONS , Use in Specific Populations].
Driving Or Operating Heavy Machinery
Inform patients that HYSINGLA ER may impair the ability
to perform potentially hazardous activities such as driving a car or operating
heavy machinery. Blood levels of hydrocodone, in some patients, may be high at
the end of 24 hours after repeated dose administration. Advise patients not to
perform such tasks until they know how they will react to the medication [see
WARNINGS AND PRECAUTIONS].
Advise patients of the potential for severe constipation,
including management instructions and when to seek medical attention. Instruct
patients to monitor their analgesic response following the use of strong laxatives
and to contact the prescriber if changes are noted [see ADVERSE REACTIONS,
Disposal Of Unused HYSINGLA ER
Advise patients to dispose of any unused tablets from a
prescription as soon as they are no longer needed by flushing down the toilet.
Healthcare professionals can telephone Purdue Pharma's
Medical Services Department (1-888-726-7535) for information on this product.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Hydrocodone was evaluated for carcinogenic potential in
rats and mice. In a two-year bioassay in rats, doses up to 25 mg/kg in males
and females were administered orally and no treatment-related neoplasms were
observed (exposure is equivalent to 0.2 times the human hydrocodone dose of 120
mg/day based on AUC exposure comparisons). In a two-year bioassay in mice,
doses up to 200 mg/kg in males and 100 mg/kg in females were administered
orally and no treatment-related neoplasms were observed (exposure is equivalent
to 3.5 times and 3.0 times, respectively, the human hydrocodone dose of 120 mg/day
based on AUC exposure comparisons).
Hydrocodone was genotoxic in the mouse lymphoma assay in
the presence of rat S9 metabolic activation but not in the absence of rat
metabolic activation. However, hydrocodone was not genotoxic in the mouse
lymphoma assay with or without human S9 metabolic activation. There was no
evidence of genotoxic potential with hydrocodone in an in vitro bacterial
reverse mutation assay with Salmonella typhimurium and Escherichia coli with or
without metabolic activation or in an in vivo mouse bone marrow micronucleus
test with or without metabolic activation.
Impairment Of Fertility
No effect on fertility or general reproductive
performance was seen with oral administration of hydrocodone to male and female
rats at doses up to 25 mg/kg/day (approximately 0.06 times and 0.08 times,
respectively, the human hydrocodone dose of 120 mg/day based on AUC exposure
Use In Specific Populations
Prolonged use of opioid
analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see WARNINGS
Available data with HYSINGLA ER in pregnant women are insufficient to inform a
drug-associated risk for major birth defects and miscarriage. In animal
reproduction studies with hydrocodone in rats and rabbits no embryotoxicity or
teratogenicity was observed. However, reduced pup survival rates, reduced
fetal/pup body weights, and delayed ossification were observed at doses causing
maternal toxicity. In all of the studies conducted, the exposures in animals
were less than the human exposure [see Data].
The estimated background risk
of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse
outcomes. In the U.S. general population, the estimated background risk of
major birth defects and miscarriage in clinically recognized pregnancies is
2-4% and 15-20%, respectively.
Prolonged use of opioid
analgesics during pregnancy for medical or nonmedical purposes can result in
physical dependence in the neonate and neonatal opioid withdrawal syndrome
shortly after birth. Neonatal opioid withdrawal syndrome presents as
irritability, hyperactivity and abnormal sleep pattern, high pitched cry,
tremor, vomiting, diarrhea, and failure to gain weight. The onset, duration,
and severity of neonatal opioid withdrawal syndrome vary based on the specific
opioid used, duration of use, timing and amount of last maternal use, and rate
of elimination of the drug by the newborn. Observe newborns for symptoms of
neonatal opioid withdrawal syndrome and manage accordingly [see WARNINGS
Labor and Delivery
Opioids cross the placenta and
may produce respiratory depression and psycho-physiologic effects in neonates.
An opioid antagonist, such as naloxone, must be available for reversal of
opioid-induced respiratory depression in the neonate. HYSINGLA ER is not
recommended for use in pregnant women during or immediately prior to labor,
when use of shorter-acting analgesics or other analgesic techniques are more
appropriate. Opioid analgesics, including HYSINGLA ER, can prolong labor
through actions which temporarily reduce the strength, duration, and frequency
of uterine contractions. However, this effect is not consistent and may be
offset by an increased rate of cervical dilation, which tends to shorten labor.
Monitor neonates exposed to opioid analgesics during labor for signs of excess
sedation and respiratory depression.
No evidence of embryotoxicity
or teratogenicity was observed after oral administration of hydrocodone
throughout the period of organogenesis in rats and rabbits at doses up to 30
mg/kg/day (approximately 0.1 and 0.3 times, respectively, the human hydrocodone
dose of 120 mg/day based on AUC exposure comparisons). However, in these
studies, reduced fetal body weights and delayed ossification were observed in
rat at 30 mg/kg/day and reduced fetal body weights were observed in in rabbit
at 30 mg/kg/day (approximately 0.1 and 0.3 times, respectively, the human
hydrocodone dose of 120 mg/day based on AUC exposure comparisons). In a pre-and
post-natal development study pregnant rats were administered oral hydrocodone
throughout the period of gestation and lactation.
At a dose of 30 mg/kg/day decreased pup viability, pup
survival indices, litter size and pup body weight were observed. This dose is
approximately 0.1 times the human hydrocodone dose of 120 mg/day based on AUC
Hydrocodone is present in human milk. A published
lactation study reports 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. This lactation study did not assess breastfed infants for potential
adverse drug reactions. Lactation studies have not been conducted with
HYSINGLA, and no information is available on the effects of the drug on the
breastfed infant or the effects of the drug on milk production. Because of the
potential for serious adverse reactions, including excess sedation and
respiratory depression in a breastfed infant, advise patients that
breastfeeding is not recommended during treatment with HYSINGLA ER.
Monitor infants exposed to HYSINGLA ER through breast
milk for excess sedation and respiratory depression. Withdrawal symptoms can
occur in breastfed infants when maternal administration of an opioid analgesic
is stopped, or when breastfeeding is stopped.
Females And Males Of Reproductive Potential
Chronic use of opioids may cause reduced fertility in
females and males of reproductive potential. It is not known whether these
effects on fertility are reversible [see ADVERSE REACTIONS].
The safety and effectiveness of HYSINGLA ER in pediatric
patients have not been established.
HYSINGLA ER gradually forms a viscous hydrogel (i.e., a
gelatinous mass) when exposed to water or other fluids. Pediatric patients may
be at increased risk of esophageal obstruction, dysphagia, and choking because
of a smaller gastrointestinal lumen if they ingest HYSINGLA ER [see WARNINGS
In a controlled pharmacokinetic study, elderly subjects
(greater than 65 years) compared to young adults had similar plasma concentrations
of hydrocodone [see CLINICAL PHARMACOLOGY]. Of the 1827 subjects exposed
to HYSINGLA ER in the pooled chronic pain studies, 241 (13%) were age 65 and
older (including those age 75 and older), while 42 (2%) were age 75 and older.
In clinical trials with appropriate initiation of therapy and dose titration,
no untoward or unexpected adverse reactions were seen in the elderly patients
who received HYSINGLA ER.
In general, use caution when selecting a dosage for an
elderly patient, usually starting at the low end of the dosing range,
reflecting the greater frequency of decreased hepatic, renal, or cardiac
function and of concomitant disease or other drug therapy.
Respiratory depression is the chief risk for elderly
patients treated with opioids, and has occurred after large initial doses were
administered to patients who were not opioid-tolerant or when opioids were
coadministered with other agents that depress respiration. Titrate the dosage
of HYSINGLA ER slowly in geriatric patients and monitor closely for signs of
central nervous system and respiratory depression [see WARNINGS AND
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, care should be taken in dose selection, and
it may be useful to monitor renal function.
No adjustment in starting dose with HYSINGLA ER is
required in patients with mild or moderate hepatic impairment. Patients with
severe hepatic impairment may have higher plasma concentrations than those with
normal hepatic function [see CLINICAL PHARMACOLOGY]. Therefore, a dosage
reduction is recommended for these patients [see DOSAGE AND ADMINISTRATION].
Monitor closely for respiratory depression, sedation, and hypotension
No dose adjustment is needed in patients with mild renal
impairment. Patients with moderate or severe renal impairment or end stage
renal disease have higher plasma concentrations than those with normal renal
function [see CLINICAL PHARMACOLOGY]. Therefore, a dosage reduction is
recommended for these patients [see DOSAGE AND ADMINISTRATION]. Monitor
closely for respiratory depression, sedation, and hypotension.