Included as part of the "PRECAUTIONS" Section
Addiction, Abuse, And Misuse
EXALGO contains hydromorphone, a Schedule II controlled substance. As an opioid, EXALGO exposes
users to the risks of addiction, abuse, and misuse [see Drug Abuse And Dependence]. As modified-
release products such as EXALGO deliver the opioid over an extended period of time, there is a greater
risk for overdose and death due to the larger amount of hydromorphone present.
Although the risk of addiction in any individual is unknown, it can occur in patients appropriately
prescribed EXALGO and in those who obtain the drug illicitly. 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 EXALGO, and
monitor all patients receiving EXALGO 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 EXALGO for the proper management of pain in any given patient.
Patients at increased risk may be prescribed modified-release opioid formulations such as EXALGO, but
use in such patients necessitates intensive counseling about the risks and proper use of EXALGO along
with intensive monitoring for signs of addiction, abuse, and misuse.
Abuse or misuse of EXALGO by crushing, chewing, snorting, or injecting the dissolved product will result
in the uncontrolled delivery of hydromorphone and can result in overdose and death [see OVERDOSE].
Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal
diversion. Consider these risks when prescribing or dispensing EXALGO. 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 modifiedrelease
opioids, even when used as recommended. Respiratory depression from opioid use, 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 OVERDOSE]. 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
EXALGO, the risk is greatest during the initiation of therapy or following a dosage increase. Closely
monitor patients for respiratory depression, especially within the first 24-72 hours of initiating therapy with
EXALGO and following dosage increases.
To reduce the risk of respiratory depression, proper dosing and titration of EXALGO are essential [see DOSAGE AND ADMINISTRATION]. Overestimating the EXALGO dose when converting patients from
another opioid product can result in fatal overdose with the first dose.
Accidental ingestion of even one dose of EXALGO, especially by children, can result in respiratory
depression and death due to an overdose of hydromorphone.
Neonatal Opioid Withdrawal Syndrome
Prolonged use of EXALGO 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 , PATIENT INFORMATION].
Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants
Profound sedation, respiratory depression, coma, and death may result from the concomitant use of
EXALGO 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 INTERACTIONS].
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
EXALGO 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 EXALGO 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
EXALGO 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 EXALGO [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 EXALGO and when EXALGO is
given concomitantly with other drugs that depress respiration [see Life-threatening Respiratory Depression, Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants ].
Alternatively, consider the use of non-opioid analgesics in these patients.
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.
EXALGO 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 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 EXALGO. In patients with circulatory shock,
EXALGO may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the
use of EXALGO in patients with circulatory shock.
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), EXALGO 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 EXALGO.
Opioids may also obscure the clinical course in a patient with a head injury. Avoid the use of EXALGO in
patients with impaired consciousness or coma.
Risks Of Use In Patients With Gastrointestinal Conditions
EXALGO is contraindicated in patients with known or suspected gastrointestinal obstruction, including
paralytic ileus. Avoid the use of EXALGO in patients with other GI obstruction.
Because the EXALGO tablet is nondeformable and does not appreciably change in shape in the GI tract,
EXALGO is contraindicated in patients with preexisting severe gastrointestinal narrowing (pathologic or
iatrogenic, for example: esophageal motility disorders, small bowel inflammatory disease, “short gut”
syndrome due to adhesions or decreased transit time, past history of peritonitis, cystic fibrosis, chronic
intestinal pseudoobstruction, or Meckel’s diverticulum). There have been reports of obstructive symptoms
in patients with known strictures or risk of strictures, such as previous GI surgery, in association with the
ingestion of drugs in nondeformable extended-release formulations.
It is possible that EXALGO tablets may be visible on abdominal x-rays under certain circumstances,
especially when digital enhancing techniques are utilized.
The hydromorphone in EXALGO 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 Disorders
The hydromorphone in EXALGO 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 EXALGO
Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial
agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic,
including EXALGO. 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 EXALGO, gradually taper the dose [see DOSAGE AND ADMINISTRATION]. Do not
abruptly discontinue EXALGO [see Drug Abuse And Dependence].
EXALGO contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including
anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible
people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably
low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people [see ADVERSE REACTIONS].
Risks Of Driving And Operating Machinery
EXALGO may impair the mental and/or physical abilities needed to perform potentially hazardous
activities such as driving a car or operating machinery. Warn patients not to drive or operate dangerous
machinery unless they are tolerant to the effects of EXALGO and know how they will react to the
medication [see 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 EXALGO, even when taken as recommended, can result in addiction,
abuse, and misuse, which can lead to overdose or death [see WARNINGS AND PRECAUTIONS]. Instruct
patients not to share EXALGO with others and to take steps to protect EXALGO from theft or misuse.
Life-threatening Respiratory Depression
Inform patients of the risk of life-threatening respiratory depression, including information that the risk is
greatest when starting EXALGO or when the dose is increased, and that it can occur even at
recommended doses [see WARNINGS AND PRECAUTIONS]. Advise patients how to recognize respiratory
depression and to seek medical attention if breathing difficulties develop.
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 EXALGO securely
and to dispose of unused EXALGO by flushing the tablets down the toilet.
Interactions With Benzodiazepines And Other CNS Depressants
Inform patients and caregivers that potentially fatal additive effects may occur if EXALGO 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 INTERACTIONS].
Inform patients that EXALGO 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 EXALGO while using any drugs that inhibit monoamine oxidase. Patients
should not start MAOIs while taking EXALGO [see DRUG INTERACTIONS].
Inform patients that EXALGO 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 EXALGO, including the following:
- EXALGO is designed to work properly only if swallowed intact. Taking cut, broken, chewed, crushed,
or dissolved EXALGO tablets can result in a fatal overdose [see DOSAGE AND ADMINISTRATION].
- Using EXALGO exactly as prescribed to reduce the risk of life-threatening adverse reactions (e.g.,
- Do not discontinue EXALGO without first discussing the need for a tapering regimen with the
prescriber [see DOSAGE AND ADMINISTRATION].
Advise patients that people with certain stomach or intestinal problems such as narrowing of the
intestines or previous surgery may be at higher risk of developing a blockage. Symptoms include
abdominal distension, abdominal pain, severe constipation, or vomiting. Instruct patients to contact their
healthcare provider immediately if they develop these symptoms.
Inform patients that EXALGO 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).
Inform patients that anaphylaxis has been reported with ingredients contained in EXALGO. Advise
patients how to recognize such a reaction and when to seek medical attention [see CONTRAINDICATIONS , WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].
Neonatal Opioid Withdrawal Syndrome
Inform female patients of reproductive potential that prolonged use of EXALGO 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 EXALGO 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 EXALGO [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 Use In Specific Populations].
Driving Or Operating Heavy Machinery
Inform patients that EXALGO may impair the ability to perform potentially hazardous activities such as
driving a car or operating heavy machinery. 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 [see ADVERSE REACTIONS , CLINICAL PHARMACOLOGY].
Disposal Of Unused EXALGO
Advise patients to flush the unused tablets down the toilet when EXALGO is no longer needed.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term studies to evaluate the carcinogenic potential of hydromorphone hydrochloride were
completed in both Han-Wistar rats and Crl:CD1®(ICR) mice. Hydromorphone HCl was administered to
Han-Wistar rats (2, 5, and 15 mg/kg/day for males, and 8, 25 and 75 mg/kg/day for females) for 2 years
by oral gavage. In female rats, incidences of hibernoma (tumor of brown fat) were increased at 10.5 times
the maximum recommended daily exposure based on AUC at the mid dose (2 tumor, 25 mg/kg/day) and
53.7 times the maximum recommended human daily exposure based on AUC at the maximum dose
(4 tumors, 75 mg/kg/day). The clinical relevance of this finding to humans has not been established.
There was no evidence of carcinogenicity in male rats. The systemic drug exposure (AUC, ng•h/mL) at
the 15 mg/kg/day in male rats was 7.6 times greater than the human exposure at a single dose of
32 mg/day of EXALGO. There was no evidence of carcinogenic potential in Crl:CD1®(ICR) mice
administered hydromorphone HCl at doses up to 15 mg/kg/day for 2 years by oral gavage. The systemic
drug exposure (AUC, ng•h/mL) at the 15 mg/kg/day in mice was 1.1 (in males) and 1.2 (in females) times
greater than the human exposure at a single dose of 32 mg/day of EXALGO.
Hydromorphone was not mutagenic in the in vitro bacterial reverse mutation assay (Ames assay).
Hydromorphone was not clastogenic in either the in vitro human lymphocyte chromosome aberration
assay or the in vivo mouse micronucleus assay.
Impairment Of Fertility
Reduced implantation sites and viable fetuses were noted at 2.1 times the human daily dose of
32 mg/day in a study in which female rats were treated orally with 1.75, 3.5, or 7 mg/kg/day
hydromorphone hydrochloride (0.7, 1.4, or 2.8 times a human daily dose of 24 mg/day (HDD) based on
body surface area) beginning 14 days prior to mating through Gestation Day 7 and male rats were treated
with the same hydromorphone hydrochloride doses beginning 28 days prior to and throughout mating.
Use In Specific Populations
Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome
[see WARNINGS AND PRECAUTIONS]. There are no adequate and well-controlled studies in pregnant
women. Based on animal data, advise pregnant women of the potential risk to a fetus.
In animal reproduction studies, reduced postnatal survival of pups, developmental delays, and altered
behavioral responses were noted following oral treatment of pregnant rats with hydromorphone during
gestation and through lactation at doses 2.1 times the human daily dose of 32 mg/day (HDD),
respectively. In published studies, neural tube defects were noted following subcutaneous injection of
hydromorphone to pregnant hamsters at doses 4.8 times the HDD and soft tissue and skeletal
abnormalities were noted following subcutaneous continuous infusion of 2.3 times the HDD to pregnant
mice. No malformations were noted at 2.1 or 17 times the HDD in pregnant rats or rabbits, respectively
[see Data]. Based on animal data, advise pregnant women of the potential risk to a fetus.
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.
Fetal/Neonatal Adverse Reactions
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 AND PRECAUTIONS].
Labor or 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. EXALGO 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 EXALGO 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
Pregnant rats were treated with hydromorphone hydrochloride from Gestation Day 6 to 17 via oral gavage
doses of 1.75, 3.5, or 7 mg/kg/day (0.5, 1.1, or 2.1 times the HDD of 32 mg/day based on body surface
area, respectively). Maternal toxicity was noted in all treatment groups (reduced food consumption and
body weights in the two highest dose groups). There was no evidence of malformations or embryotoxicity
Pregnant rabbits were treated with hydromorphone hydrochloride from Gestation Day 6 to 20 via oral
gavage doses of 10, 25, or 50 mg/kg/day (4.3, 8.5, or 17 times the HDD of 32 mg/day based on body
surface area, respectively). Maternal toxicity was noted in the highest dose group (reduced food
consumption and body weights). There was no evidence of malformations or embryotoxicity reported.
In a published study, neural tube defects (exencephaly and cranioschisis) were noted following
subcutaneous administration of hydromorphone hydrochloride (19 to 258 mg/kg) on Gestation Day 8 to
pregnant hamsters (4.8 to 65.4 times the HDD of 32 mg/day based on body surface area). The findings
cannot be clearly attributed to maternal toxicity. No neural tube defects were noted at 14 mg/kg (3.5 times
the human daily dose of 32 mg/day). In a published study, CF-1 mice were treated subcutaneously with
continuous infusion of 7.5, 15, or 30 mg/kg/day hydromorphone hydrochloride (1.1, 2.3, or 4.6 times the
human daily dose of 32 mg based on body surface area) via implanted osmotic pumps during
organogenesis (Gestation Days 7 to 10). Soft tissue malformations (cryptorchidism, cleft palate,
malformed ventricles and retina), and skeletal variations (split supraoccipital, checkerboard and split
sternebrae, delayed ossification of the paws and ectopic ossification sites) were observed at doses 2.3
times the human dose of 32 mg/day based on body surface area. The findings cannot be clearly
attributed to maternal toxicity.
Pregnant rats were treated with hydromorphone hydrochloride from Gestation Day 6 to Lactation Day 21
via oral gavage doses of 1.75, 3.5, or 7 mg/kg/day (0.5, 1.1, or 2.1 times the HDD of 32 mg/day based on
body surface area, respectively). Reduced pup weights were noted at 1.1 and 2.1 times the human daily
dose of 32 mg/day and increased pup deaths, delayed ear opening, reduced auditory startle reflex, and
reduced open-field activity were also noted at 2.1 times the HDD. Maternal toxicity was noted in all
treatment groups (reduced food consumption and body weights in all groups) and decreased maternal
care in the high dose group.
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 EXALGO. Low concentrations of hydromorphone have been detected in human milk in clinical trials.
Withdrawal symptoms can occur in breastfeeding infants when maternal administration of an opioid
analgesic is stopped. Nursing should not be undertaken while a patient is receiving EXALGO since
hydromorphone is excreted in the milk.
Monitor infants exposed to EXALGO 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 breast-feeding 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 , Nonclinical Toxicology].
The safety and effectiveness of EXALGO in patients 17 years of age and younger have not been
Elderly patients (aged 65 years or older) may have increased sensitivity to hydromorphone. 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 EXALGO slowly in geriatric
patients and monitor closely for signs of central nervous system and respiratory depression [see WARNINGS AND PRECAUTIONS].
Hydromorphone 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
In a study that used a single 4 mg oral dose of immediate-release hydromorphone tablets, four-fold
Increases in plasma levels of hydromorphone (Cmax and AUC0-∞) were observed in patients with moderate
hepatic impairment (Child-Pugh Group B). Start patients with moderate hepatic impairment on 25% of the
EXALGO dose that would be used in patients with normal hepatic function. Closely monitor patients with
moderate hepatic impairment for respiratory and central nervous system depression during initiation of
therapy with EXALGO and during dose titration. The pharmacokinetics of hydromorphone in severe
hepatic impairment patients have not been studied. As further increases in Cmax and AUC0-∞ of
hydromorphone in this group are expected, use of alternate analgesics is recommended [see DOSAGE AND ADMINISTRATION].
Administration of a single 4 mg dose of immediate-release hydromorphone tablets resulted in two-fold
and four-fold increases in plasma levels of hydromorphone (Cmax and AUC0-48h) in moderate (CLcr = 40 to
60 mL/min) and severe (CLcr < 30 mL/min) impairment, respectively. In addition, in patients with severe
renal impairment hydromorphone appeared to be more slowly eliminated with longer terminal elimination
half-life. Start patients with moderate renal impairment on 50% and patients with severe renal impairment
on 25% of the EXALGO dose that would be prescribed for patients with normal renal function. Closely
monitor patients with renal impairment for respiratory and central nervous system depression during
initiation of therapy with EXALGO and during dose titration. As EXALGO is only intended for once daily
administration, consider use of an alternate analgesic that may permit more flexibility with the dosing
interval in patients with severe renal impairment [see DOSAGE AND ADMINISTRATION].