Long-acting (Exalgo) is indicated for the management of pain in opioid tolerant patients

severe enough to require daily, around-the-clock, long-term opioid treatment and for which
alternative treatment options are inadequate

Opioid tolerant patients only (extended-release:) 8-64 mg PO qDay; may administer a starting
dose equivalent to patient's total daily oral hydromorphone dose administered once daily with
or without food

Should address pain relief and adverse events frequently; increase dose no more frequently
than q3-4days; may titrate with increases of 25-50% of current daily dose; consider
increasing dose if more than 2 doses of rescue medications are needed within 24hr within 2
consecutive days

Extented-release tablets should be swallowed whole; crushing, dividing, or dissolving will

release opioid content all at once and increase risk of respiratory depression and death

Converting to Exalgo

 Conversion from other oral hydromorphone formulations: Start with equivalent total
daily dose of immediate release formulation and administer once daily; may titrate q3-
4days until adequate pain relief with tolerable adverse effects achieved
 Conversion from other opioids: Start Exalgo dose at 50% of calculated daily dose
q24hr; titrate until adequate pain relief with tolerable adverse effects achieved
 Conversion from transdermal fentanyl to Exalgo: Start Exalgo 18 hr after removal of
transdermal fentanyl patch at 50% of calculated total daily dose given over 24hr; for a
25 mcg/hr fentanyl patch the equianalgesic dose is 12 mg PO q24hr
 Discontinuation of Exalgo therapy: Taper gradually by decreasing dose by 25-50%
q2-3days to a dose of 8 mg PO q24hr before discontinuing

Opioid-tolerant definition

 Use of higher starting doses in patients who are not opioid tolerant may cause fatal
respiratory depression
 Patients who are opioid tolerant are those receiving, for 1 week or longer, at least 60
mg/day PO morphine, 25 mcg/hr transdermal fentanyl, 30 mg/day PO oxycodone, 8
mg/day PO hydromorphone, 25 mg/day PO oxymorphone, or an equianalgesic dose of
another opioid

Limitations of use

 Because of the risks of addiction, abuse, and misuse with opioids, even at
recommended doses, and because of the greater risks of overdose and death with
extended-release opioid formulations, reserve for patients whom alternative treatment
options (eg, nonopioid analgesics or immediate-release opioids) are ineffective, not
tolerated, or would be otherwise inadequate to provide sufficient management of pain
 Not indicated for acute pain or as a PRN analgesic
Medscape

Dosage Forms & Strengths

Adult

tablet: Schedule II

 2mg
 4mg
 8mg

tablet, extended-release: Schedule II

 8mg
 12mg
 16mg
 32mg

injection solution

 1mg/mL
 2mg/mL
 4mg/mL

injection solution, preservative free: Schedule II

 10mg/mL

oral liquid: Schedule II

 5mg/5mL

suppository: Schedule II

 3mg

Prefilled syringe: Schedule II

 0.2 mg/mL
 0.6 mg/mL

Moderate-to-Severe Pain

Indicated for moderate-to-severe pain

PO

 Immediate-release: 2-4 mg q4-6hr PRN; a gradual increase in dose may be required

 Oral liquid (usual dose): 2.5-10 mg (2.5-10 mL) q3-6hr PRN

SC/IM
  1-2 mg q2-3hr PRN; adjust dose according to pain and adverse effects
 IM dose not recommended for use as it may result in variable absorption and lag time
to peak effect

IV

 Opioid naive: 0.2-1 mg IV q2-3hr PRN; may require higher doses in patients with
prior opioid exposure
 Critically ill patients (opiate-naive patients): 0.2-0.6 mg q1-2hr PRN given slowly
over 2-3 minutes; patients with previous opiate exposure may tolerate higher doses
 Continuous infusion: 0.5-3 mg/hr, titrated to response

Patient-controlled analgesia

 Usual concentration, 0.2 mg/mL; demand dose, 0.1-0.2 mg; dose range is 0.05-0.4 mg
 Lockout interval: 5-10 minutes

Rectal

 3 mg PR q6-8hr

Pediatric dose

Dosage Forms & Strengths

tablet: Schedule II

 2mg
 4mg
 8mg

oral liquid: Schedule II

 5mg/5mL

injection solution

 1mg/mL
 2mg/mL
 4mg/mL

suppository: Schedule II

 3mg

Pain (Off-label)

Moderate-to-severe pain

Children: 0.03-0.08 mg/kg PO q4-6hr PRN; not to exceed 5 mg/dose

Adolescents: 1-4 mg/dose PO q4-6hr PRN

Children: 0.015 mg/kg IV q4-6hr PRN

Adolescents: 1-2 mg/dose IV/IM.SC q4-6hr

Patient Controlled Anesthesia (Off-label)

Loading dose: 8 mcg/kg IV bolus

Demand dose (initial): 2 mcg/kg IV with a lockout time of 10 min

Chronic Severe Pain

Long-acting (Exalgo) is indicated for the management of pain in opioid tolerant patients
severe enough to require daily, around-the-clock, long-term opioid treatment and for which
alternative treatment options are inadequate

Opioid tolerant patients only (extended-release:) 8-64 mg PO qDay; may administer a starting
dose equivalent to patient's total daily oral hydromorphone dose administered once daily with
or without food

Should address pain relief and adverse events frequently; increase dose no more frequently
than q3-4days; may titrate with increases of 25-50% of current daily dose; consider
increasing dose if more than 2 doses of rescue medications are needed within 24hr within 2
consecutive days

Extented-release tablets should be swallowed whole; crushing, dividing, or dissolving will

release opioid content all at once and increase risk of respiratory depression and death

Converting to Exalgo

 Conversion from other oral hydromorphone formulations: Start with equivalent total
daily dose of immediate release formulation and administer once daily; may titrate q3-
4days until adequate pain relief with tolerable adverse effects achieved
 Conversion from other opioids: Start Exalgo dose at 50% of calculated daily dose
q24hr; titrate until adequate pain relief with tolerable adverse effects achieved
 Conversion from transdermal fentanyl to Exalgo: Start Exalgo 18 hr after removal of
transdermal fentanyl patch at 50% of calculated total daily dose given over 24hr; for a
25 mcg/hr fentanyl patch the equianalgesic dose is 12 mg PO q24hr
 Discontinuation of Exalgo therapy: Taper gradually by decreasing dose by 25-50%
q2-3days to a dose of 8 mg PO q24hr before discontinuing

Opioid-tolerant definition

 Use of higher starting doses in patients who are not opioid tolerant may cause fatal
respiratory depression
 Patients who are opioid tolerant are those receiving, for 1 week or longer, at least 60
mg/day PO morphine, 25 mcg/hr transdermal fentanyl, 30 mg/day PO oxycodone, 8
mg/day PO hydromorphone, 25 mg/day PO oxymorphone, or an equianalgesic dose of
another opioid

Limitations of use

 Because of the risks of addiction, abuse, and misuse with opioids, even at
recommended doses, and because of the greater risks of overdose and death with
extended-release opioid formulations, reserve for patients whom alternative treatment
 options (eg, nonopioid analgesics or immediate-release opioids) are ineffective, not
tolerated, or would be otherwise inadequate to provide sufficient management of pain
 Not indicated for acute pain or as a PRN analgesic

Cough (Off-label)

1 mg PO q3-4hr PRN

Contraindicated (1)

 alvimopan

alvimopan, hydromorphone. receptor binding competition. Contraindicated.

Alvimopan is contraindicated in opioid tolerant patients (ie, those who have taken
therapeutic doses of opioids for >7 consecutive days immediately prior to taking
alvimopan). Patients recently exposed to opioids are expected to be more sensitive to
the effects of alvimopan and therefore may experience abdominal pain, nausea and
vomiting, and diarrhea. No significant interaction is expected with concurrent use of
opioid analgesics and alvimopan in patients who received opioid analgesics for 7 or
fewer consecutive days prior to alvimopan.

Serious - Use Alternative (40)

 benzhydrocodone/acetaminophen
 bremelanotide
 buprenorphine
 buprenorphine buccal
 butorphanol
 cimetidine
 citalopram
 clonidine
 eluxadoline
 escitalopram
 fentanyl
 fentanyl intranasal
 fentanyl iontophoretic transdermal system
 fentanyl transdermal
 fentanyl transmucosal
 fluoxetine
 fluvoxamine
 hydrocodone
 isocarboxazid
 linezolid
 lumefantrine
 methylene blue
 nalbuphine
 paroxetine
 pentazocine
 phenelzine
 prasugrel
 procarbazine
 quinidine
 rasagiline
 selegiline
 selegiline transdermal
 sertraline
 sodium oxybate
  sufentanil SL
 ticagrelor
 tramadol
 tranylcypromine
 valerian
 vortioxetine

Monitor Closely (202)

 albuterol
 alfentanil
 alprazolam
 amiodarone
 amitriptyline
 amobarbital
 amoxapine
 apomorphine
 arformoterol
 aripiprazole
 armodafinil
 artemether/lumefantrine
 asenapine
 azelastine
 baclofen
 belladonna and opium
 benperidol
 benzphetamine
 brexanolone
 brompheniramine
 buprenorphine
 buprenorphine buccal
 buprenorphine, long-acting injection
 bupropion
 butabarbital
 butalbital
 butorphanol
 caffeine
 carbinoxamine
 carisoprodol
 celecoxib
 chloral hydrate
 chlordiazepoxide
 chloroquine
 chlorpheniramine
 chlorpromazine
 chlorzoxazone
 cimetidine
 cinnarizine
 clemastine
 clobazam
 clomipramine
 clonazepam
 clorazepate
 clozapine
 codeine
 cyclizine
 cyclobenzaprine
 cyproheptadine
 dantrolene
 darifenacin
 desflurane
 desipramine
 desvenlafaxine
 deutetrabenazine
 dexchlorpheniramine
 dexfenfluramine
 dexmedetomidine
 dexmethylphenidate
 dextroamphetamine
 dextromoramide
 diamorphine
 diazepam
 dichlorphenamide
 diethylpropion
 difenoxin hcl
 dimenhydrinate
 diphenhydramine
 diphenoxylate hcl
 dipipanone
 dobutamine
 dopamine
 dopexamine
 dosulepin
 doxepin
 doxylamine
 dronedarone
 droperidol
 duloxetine
 eltrombopag
 ephedrine
 ephedrine (pulmonary)
 epinephrine
 epinephrine racemic
 esketamine intranasal
 estazolam
 ethanol
 etomidate
 fenfluramine
 flibanserin
 fluphenazine
 flurazepam
 formoterol
 haloperidol
 hydroxyzine
 iloperidone
 imipramine
 isoproterenol
 ketamine
 ketotifen, ophthalmic
 levalbuterol
 levorphanol
 lisdexamfetamine
 lofepramine
 lofexidine
 loprazolam
 lorazepam
 lormetazepam
 loxapine
 loxapine inhaled
 lurasidone
 maprotiline
 maraviroc
 marijuana
 melatonin
 meperidine
 meprobamate
 metaproterenol
 metaxalone
 methadone
 methamphetamine
 methocarbamol
 methylenedioxymethamphetamine
 midazolam
 midazolam intranasal
 midodrine
 mirtazapine
 modafinil
 morphine
 motherwort
 moxonidine
 nabilone
 nalbuphine
 norepinephrine
 nortriptyline
 olanzapine
 opium tincture
 orphenadrine
 oxazepam
 oxycodone
 oxymorphone
 paliperidone
 papaveretum
 papaverine
 parecoxib
 pegvisomant
 pentazocine
 pentobarbital
 perampanel
 perphenazine
 phendimetrazine
 phenobarbital
 phentermine
 phenylephrine
 phenylephrine PO
 pholcodine
 pimozide
 pirbuterol
 primidone
 prochlorperazine
 promethazine
 propafenone
  propofol
 propylhexedrine
 protriptyline
 pseudoephedrine
 quazepam
 quetiapine
 quinacrine
 ramelteon
 ranolazine
 risperidone
 ritonavir
 salmeterol
 scullcap
 secobarbital
 sertraline
 sevoflurane
 shepherd's purse
 stiripentol
 sufentanil
 suvorexant
 tapentadol
 temazepam
 terbutaline
 thioridazine
 thiothixene
 tipranavir
 topiramate
 tramadol
 trazodone
 triazolam
 triclofos
 trifluoperazine
 trimipramine
 triprolidine
 venlafaxine
 xylometazoline
 yohimbine
 ziconotide
 ziprasidone
 zotepine

Minor (6)

 brimonidine
 dextroamphetamine
 eucalyptus
 lidocaine
 sage
 ziconotide

Adverse Effects

Frequency Not Defined

Anticholinergic: Dry mouth, palpitation, tachycardia, urinary retention

Cardiovascular: Angina pectoris, bradycardia, cardiac arrest, circulatory depression,
myocardial infarction, QT-interval prolongation, severe cardiac arrhythmias, shock, ST-
segment elevation, syncope, ventricular tachycardia

Central nervous system (CNS): Agitation, coma, dizziness, dysphoria, mental clouding or
depression, euphoria, faintness, nervousness, restlessness, sedation, seizures, visual
disturbances, weakness

Gastrointestinal (GI): Constipation, nausea, vomiting, anorexia, abdominal distention,

bilieary tract spasm, decreased appetite, decreased intestinal motility, gastroesophageal reflux
disease, paralytic ileus,

Respiratory: Respiratory depression, respiratory arrest, hypoxia, bronchospasm, dyspnea,

rhinorrhea, flu-like symptoms (Exalgo)

Other: Flushing, pruritus, sweating, urticaria, skin rash, hyperhidrosis, warmness of

face/neck/upper thorax

Postmarketing Reports

Confusional state, convulsions, drowsiness, dyskinesia, erectile dysfunction, fatigue, hepatic

enzymes increased, hyperalgesia, hypersensitivity reaction, lethargy, myoclonus,
oropharyngeal swelling, peripheral edema, and somnolence, serotonin syndrome, adrenal
insufficiency, anaphylaxis, androgen deficiency

Warnings

Black Box Warnings

Opioid analgesic risk evaluation and mitigation strategy (REMS)

 To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse,
the Food and Drug Administration (FDA) has required a REMS for these products; under
requirements of the REMS, drug companies with approved opioid analgesic products must
make REMS-compliant education programs available to healthcare providers
 Healthcare providers are strongly encouraged to:
o Complete a REMS-compliant education program
o Counsel patients and/or their caregivers, with every prescription, on safe use,
serious risks, storage, and disposal of these products
o Emphasize to patients and their caregivers the importance of reading the
Medication Guide every time it is provided by their pharmacist
o Consider other tools to improve patient, household, and community safety

Hydromorphone high-potency formulation

 Hydromorphone high-potency injection is highly concentrated solution of hydromorphone, a

potent Schedule II controlled opioid agonist intended for use in opioid-tolerant patients; it is
not to be confused with standard parenteral formulations of hydromorphone or other
opioids; overdose and death could result
 Use caution to avoid confusing the highly concentrated (Dilaudid-HP) injection with the less
concentrated (Dilaudid) injectable product
 Schedule II opioid agonists (eg, morphine, oxymorphone, oxycodone, fentanyl, methadone)
have highest potential for abuse and risk of producing respiratory depression
 Alcohol, other opioids, and CNS depressants (eg, sedative-hypnotics) potentiate respiratory
depressant effects of hydromorphone, increasing risk of respiratory depression that might
result in death
 Accidental intake may lead to fatal overdose, especially in children High potential for abuse
Risk of medication errors

 Ensure accuracy when prescribing, dispensing, and administering oral Solution; dosing errors
due to confusion between mg and mL can result in accidental overdose and death

Addiction, abuse, and misuse

 Risk of opioid addiction, abuse, and misuse, which can lead to overdose and death
 Assess each patient’s risk prior to prescribing and monitor all patients regularly for the
development of these behaviors or conditions

Life-threatening respiratory depression

 Serious, life-threatening, or fatal respiratory depression may occur

 Monitor for respiratory depression, especially during initiation or following a dose increase
 Instruct patients to swallow tablet/capsule whole; crushing, chewing, or dissolving can cause
rapid release and absorption of a potentially fatal dose

Accidental exposure

 Accidental of even 1 dose, especially by children, can result in a fatal overdose

Neonatal opioid withdrawal syndrome

 Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which
may be life-threatening if not recognized and treated, and requires management according
to protocols developed by neonatology experts
 Syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry,
tremor, vomiting, diarrhea and failure to gain weight
 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
 If opioid use is required for a prolonged period in a pregnant woman, advise the patient of
the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will
be available

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.
 Reserve concomitant prescribing of oral solution or tablets and benzodiazepines or other
CNS depressants for use in patients for whom alternative treatment options are inadequate
 Limit dosages and durations to the minimum required
 Follow patients for signs and symptoms of respiratory depression and sedation

Contraindications

Hypersensitivity

Dilaudid Liquid and Tablets

 Obstetrical analgesia
 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 hydromorphone, hydromorphone salts, any other components of the
product, or sulfite-containing medications (e.g., anaphylaxis)

Suppository

 Increased intracranial pressure resulting from intracranial lesion; conditions resulting in

depressed ventilatory function including COPD, emphysema, status asthmaticus,
kyphoscoliosis, cor pulmonale

Dilaudid injection

 Dilaudid HP: Paralytic ileus, opioid nontolerant patients, known ro suspected pre-existing GI
surgery or diseases resulting in narrowing of GI tract loops in the GI tract or GI obstruction
 Dilaudid HP is contraindicated in non-opioid tolerant patients

Extended-release (Exalgo)

 Opioid nontolerant patients

 Paralytic ileus, opioid nontolerant patients, known ro suspected pre-existing GI surgery or
diseases resulting in narrowing of GI tract loops in the GI tract or GI obstruction
 Significant respiratory depression
 Acute or severe bronchial asthma

Cautions

Dosing errors can result in accidental overdose and death; ensure dose is communicated
clearly and dispensed accurately; a household teaspoon or tablespoon is not an adequate
measuring device; given inexactitude of household spoon measure and possibility of using a
tablespoon instead of a teaspoon, which could lead to overdosage, the enclosed measuring
device should be used or a calibrated measuring device obtained from the pharmacist; health
care providers should recommend a calibrated device that can measure and deliver the
prescribed dose accurately, and instruct caregivers to use extreme caution in measuring the
dosage

The oral solution or tablets are contraindicated in patients with known or suspected
gastrointestinal obstruction, including paralytic ileus; may cause spasm of sphincter of Oddi;
opioids may cause increases in serum amylase; monitor patients with biliary tract disease,
including acute pancreatitis, for worsening symptoms

Avoid 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; mixed agonist/antagonist and partial agonist analgesics may reduce
analgesic effect and/or precipitate withdrawal symptoms

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; monitor such patients closely, particularly when initiating and
titrating dosages

When discontinuing therapy in a physically-dependent patient, gradually taper the dosage

May impair physical or mental abilities; use caution when performing work that require
mental alertness such as operating machinery or driving

Myoclonus and seizures reported with high doses; use caution in patients with history of
seizure disorders
Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative
opioid agonists, including codeine, hydrocodone, levorphanol, oxycodone, oxymorphone

May cause hyptension especially in patients with cardiovascular disease or hypovolemia; may
cause severe hyptension, including orthostatic hypotension and syncope; use caution in
patients taking drugs that may exagerate hypotensive effects, including phenothiazines or
general anesthetics; avoid use in patients with circultory shock; may reduce cardiac output
and blood pressure

May prevent diagnosis of patients with acute abdominal conditions

Use caution in patients with biliary tract dysfunction

Use cautioin in patients with inflammatory or obstructive bowel disorder, acute pancreatitis
secondary to biliary tract disease, and patients undergoing biliary surgery

Cases of adrenal insufficiency have been reported with opioid use, more often following
greater than one month of use; if adrenal insufficiency suspected, confirm diagnosis with
diagnostic testing as soon as possible; if diagnosed, treat with physiologic replacement doses
of corticosteroids; wean patient off of 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 different opioid without recurrence of adrenal insufficiency

In patients who may be susceptible to intracranial effects of CO2 retention (eg, those with
evidence of increased intracranial pressure or brain tumors), therapy may reduce respiratory
drive, and resultant CO2 retention can further increase intracranial pressure; monitor such
patients for signs of sedation and respiratory depression, particularly when initiating therapy

Use cuation in delirium tremens

Long-term opioid use may cause secondary hypogonadism, which may lead to sexual
dysfunction, infertility, mood disorders, and osteoporosis

Use caution in renal/hepatic impairment, obesity, prostatic hyperplasia/urinary stricture,

psychoses, respiratory disease or thyroid dysfunction

Use within 14 days of MAO intake not recommended

Controlled-release formulation should only be used when continuous analgesia is required

over an extended period of time; not for use PRN

IM formulation may result in variable absorption and a lag time to peak effect

Tailor opioid-containing analgesic regimen to each patient's needs

May cause constipation; consider preventive measures to reduce potential of constipation; use
with caution in patients with chronic constipation

Use caution in patients who are morbidly obese

Some formulations may contain lactose; consider lactose content prior to initiating therapy in
patients with hereditary disease of galatose intolerance

Vial stoppers of single-dose injectable vials may contain latex

Some dosage forms may contain trace amounts of sodium metabisulfite, which may cause
allergic reactions
Opioid analgesic risk evaluation and mitigation strategy (REMS)

 To ensure that benefits of opioid analgesics outweigh risks of addiction, abuse, and misuse,
the Food and Drug Administration (FDA) has required a Risk Evaluation and Mitigation
Strategy (REMS) for these products
 Discuss the safe use, serious risks, and proper storage and disposal of opioid analgesics with
patients and/or their caregivers every time these medicines are prescribed; use the
following link to obtain the Patient Counseling Guide (PCG):
www.fda.gov/OpioidAnalgesicREMSPCG
 Emphasize to patients and their caregivers the importance of reading the Medication Guide
that they will receive from their pharmacist every time an opioid analgesic is dispensed to
them
 Consider using other tools to improve patient, household, and community safety, such as
patient-prescriber agreements that reinforce patient-prescriber responsibilities
 To obtain further information on opioid analgesic REMS and for a list of accredited REMS
CME/CE, call 1-800-503-0784, or log on to www.opioidanalgesicrems.com; the FDA Blueprint
can be found at www.fda.gov/OpioidAnalgesicREMSBlueprint

Long-acting opioids

 Schedule II opioid analgesics expose users to the risks of addiction, abuse, and misuse; there
is a greater risk for overdose and death with extended-release opioids due to the larger
amount of active opioid present (see Black Box Warnings)
 Although risk of addiction in any individual is unknown, it can occur in patients appropriately
prescribed opiates; addiction can occur at recommended dosages; assess each patient’s risk
for opioid addiction, abuse, or misuse prior to prescribing; monitor all patients receiving
therapy for the development of these behaviors and conditions; potential for these risks
should not prevent proper management of pain in any given patient; intensive monitoring is
necessary
 Serious, life-threatening, or fatal respiratory depression reported with use of opioids, even
when used as recommended; management of respiratory depression may include close
observation, supportive measures, and use of opioid antagonists, depending on patient’s
clinical status
 Risk of respiratory depression is greatest during initiation of therapy or following a dosage
increase; monitor patients closely for respiratory depression, especially within first 24-72 hr
of initiating therapy and following dosage increases
 Accidental exposure reported, including fatalities (see Black Box Warnings)
 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; 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 Black Box Warnings)
 Profound sedation, respiratory depression, coma, and death may result from concomitant
use with benzodiazepines or other CNS depressants; because of these risks, reserve
concomitant prescribing of these drugs for use in patients for whom alternative treatment
options are inadequate; if decision is made to prescribe a benzodiazepine or other CNS
depressant concomitantly with an opioid analgesic, prescribe lowest effective dosages and
minimum durations of concomitant use
 Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or
debilitated patients as they may have altered pharmacokinetics or altered clearance
compared to younger, healthier patients

Pregnancy & Lactation

Pregnancy category: C

Lactation: Drug excreted in breast milk; use not recommended

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal

risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal
studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not
available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human
fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Pharmacology

Mechanism of Action

Mu-opioid receptor agonist; inhibits ascending pain pathways, thus altering response to pain;
main therapeutic action is analgesia

Other pharmacologic effects include respiratory depression and sedation; suppresses cough
by acting centrally in medulla

Absorption

Bioavailability: 62%

Onset: 15-30 min (PO); 15 min (SC); 15 min (IM); 5 min (IV); 15-30 min (PR); 6 hr (ER)

Duration: 3-4 hr (PO/IV); extended-release (13 hr)

Peak plasma time: 30-60 min (PO); SC, 30-90 min; IM, 30-60 min; IV, 15-30 min; PR, 30-90
min

Distribution

Protein bound: 8-19%

Vd: 4 L/kg

Metabolism

Metabolized in liver to CYP2D6 via conjugation with glucuronic acid to active metabolite
only

Elimination

Half-life: 2-3 hr (immediate-release); 11 hr (extended-release)

Excretion: Urine (primarily)

Administration

IV Incompatibilities

Additive: Sodium bicarbonate, thiopental

Syringe: Ampicillin, diazepam, hyaluronidase, phenobarbital, phenytoin

Y-site: Amphotericin B cholesteryl sulfate complex, diazepam, minocycline, phenobarbital,

phenytoin, sargramostim, tetracycline, thiopental

IV/IM Administration

May be given IV, SC, or IM

Direct injection: Dilute to 4-5 mL with NS or SWI, and administer over at least 2-3 minutes
or give 2 mg over 3-5 minutes

Intermittent administration: Dilute in 50-100 mL D5W or NS, and infuse over 15-30 minutes

IV administration (eg, rapid IV push) has been associated with increased systemic effects,
especially respiratory depression and hypotension

Monitor patient constantly; keep resuscitation equipment and narcotic antagonist (eg,
naloxone) readily available

IV Preparation

Direct injection: Dilute to 4-5 mL with NS or SWI

Continuous infusion: Dilute in 100-1000 mL of D5W, NS, D5/NS, D5½NS, Ringer solution,
or LR

Solution may appear slightly yellow; this does not alter potency

Vial stopper contains latex

Storage

Store at 25°C (77°F)

Patient Education
hydromorphone rectal

HYDROMORPHONE SUPPOSITORY - RECTAL

(hye-droe-MOR-fone)

COMMON BRAND NAME(S): Dilaudid

WARNING: Hydromorphone has a risk for abuse and addiction, which can lead to overdose
and death. Hydromorphone may also cause severe, possibly fatal, breathing problems. To
lower your risk, your doctor should have you use the smallest dose of hydromorphone that
works, and use it for the shortest possible time. See also How to Use section for more
information about addiction.The risk for severe breathing problems is higher when you start
this medication and after a dose increase, or if you use the wrong dose/strength. Using this
medication with alcohol or other drugs that can cause drowsiness or breathing problems may
cause very serious side effects, including death. Be sure you know how to use
hydromorphone and what other drugs you should avoid using with it. See also Drug
Interactions section. Get medical help right away if any of these very serious side effects
occur: slow/shallow breathing, unusual lightheadedness, severe drowsiness/dizziness,
difficulty waking up.Keep this medicine in a safe place to prevent theft, misuse, or abuse. If
someone accidentally swallows this drug, get medical help right away.Before using this
medication, women of childbearing age should talk with their doctor(s) about the risks and
benefits. Tell your doctor if you are pregnant or if you plan to become pregnant. During
pregnancy, this medication should be used only when clearly needed. It may slightly increase
the risk of birth defects if used during the first two months of pregnancy. Also, using it for a
long time or in high doses near the expected delivery date may harm the unborn baby. To
lessen the risk, use the smallest effective dose for the shortest possible time. Babies born to
mothers who use this drug for a long time may develop severe (possibly fatal) withdrawal
symptoms. Tell the doctor right away if you notice any symptoms in your newborn baby such
as crying that doesn't stop, slow/shallow breathing, irritability, shaking, vomiting, diarrhea,
poor feeding, or difficulty gaining weight.

USES: Hydromorphone is used to treat moderate to severe pain. It acts on certain centers in
the brain to give you pain relief. This medication is an opioid (narcotic) pain reliever.

HOW TO USE: Wash your hands before and after using the suppository. Unwrap and insert
one suppository into the rectum as directed by your doctor. Lie down on your left side with
right knee bent. Gently push the suppository into the rectum with your finger. Remain lying
down for a few minutes, and avoid having a bowel movement for an hour or longer so the
drug will be absorbed. The suppository is for use in the rectum only.If you have nausea, ask
your doctor or pharmacist about ways to decrease nausea (such as lying down for 1 to 2 hours
with as little head movement as possible).The dosage is based on your medical condition and
response to treatment. Do not increase your dose, use the medication more frequently, or use
it for a longer time than prescribed. Properly stop the medication when so directed.Pain
medications work best if they are used when the first signs of pain occur. If you wait until the
pain has worsened, the medication may not work as well.Suddenly stopping this medication
may cause withdrawal, especially if you have used it for a long time or in high doses. To
prevent withdrawal, your doctor may lower your dose slowly. Tell your doctor or pharmacist
right away if you have any withdrawal symptoms such as restlessness, mental/mood changes
(including anxiety, trouble sleeping, thoughts of suicide), watering eyes, runny nose, nausea,
diarrhea, sweating, muscle aches, or sudden changes in behavior.When this medication is
used for a long time, it may not work as well. Talk with your doctor if this medication stops
working well.Though it helps many people, this medication may sometimes cause addiction.
This risk may be higher if you have a substance use disorder (such as overuse of or addiction
to drugs/alcohol). Use this medication exactly as prescribed to lower the risk of addiction.
Ask your doctor or pharmacist for more details.Tell your doctor if your pain does not get
better or if it gets worse.

SIDE EFFECTS: See also Warning section.Nausea, vomiting, constipation, lightheadedness,

dizziness, drowsiness, increased sweating, or dry mouth may occur. If any of these effects
persist or worsen, tell your doctor or pharmacist promptly.To prevent constipation, eat dietary
fiber, drink enough water, and exercise. You may also need to take a laxative. Ask your
pharmacist which type of laxative is right for you.Remember that your doctor has prescribed
this medication because he or she has judged that the benefit to you is greater than the risk of
side effects. Many people using this medication do not have serious side effects.Tell your
doctor right away if you have any serious side effects, including: mental/mood changes (such
as agitation, hallucinations, confusion), difficulty urinating, vision changes, slow/fast
heartbeat, severe stomach/abdominal pain, signs of your adrenal glands not working well
(such as loss of appetite, unusual tiredness, weight loss).Get medical help right away if you
have any very serious side effects, including: slow/shallow breathing, fainting, seizures,
severe drowsiness/difficulty waking up.A very serious allergic reaction to this drug is rare.
However, get medical help right away if you notice any symptoms of a serious allergic
reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe
dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice
other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor
for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-
1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about
side effects. You may report side effects to Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using hydromorphone, tell your doctor or pharmacist if you are
allergic to it; or to other opioid pain medications (such as hydrocodone, morphine); or if you
have any other allergies. This product may contain inactive ingredients, which can cause
allergic reactions or other problems. Talk to your pharmacist for more details.Before using
this medication, tell your doctor or pharmacist your medical history, especially of: kidney
disease, liver disease, lung disease (such as asthma, chronic obstructive pulmonary disease-
COPD), a certain spinal problem (kyphoscoliosis), breathing problems (such as slow/shallow
breathing, sleep apnea), certain heart problems (irregular heartbeat), personal or family
history of a substance use disorder (such as overuse of or addiction to drugs/alcohol), brain
disorders (such as seizures, head injury, tumor, increased intracranial pressure), underactive
thyroid (hypothyroidism), difficulty urinating (for example, due to enlarged prostate or
narrowed urethra), disease of the pancreas (such as pancreatitis), mental/mood disorders
(such as toxic psychosis), gallbladder disease, adrenal gland problem (such as Addison's
disease), intestinal disorders (such as colitis, blockage, paralytic ileus, infectious
diarrhea).This drug may make you dizzy or drowsy. Alcohol or marijuana (cannabis) can
make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs
alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are
using marijuana (cannabis).To lower your risk of dizziness and lightheadedness, get up
slowly when rising from a sitting or lying position.Before having surgery, tell your doctor or
dentist that you are using this medication.Older adults may be more sensitive to the side
effects of this drug, especially confusion, dizziness, drowsiness, and slow/shallow
breathing.During pregnancy, this medication should be used only when clearly needed. It
may harm an unborn baby. Discuss the risks and benefits with your doctor. (See also Warning
section.)This drug passes into breast milk and the effect on a nursing infant is not known.
Discuss the risks and benefits with your doctor before breast-feeding.

DRUG INTERACTIONS: See also Warning section.Drug interactions may change how your
medications work or increase your risk for serious side effects. This document does not
contain all possible drug interactions. Keep a list of all the products you use (including
prescription/nonprescription drugs and herbal products) and share it with your doctor and
pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's
approval.Some products that may interact with this drug include: certain pain medications
(mixed opioid agonist-antagonists such as pentazocine, nalbuphine, butorphanol),
naltrexone.The risk of serious side effects (such as slow/shallow breathing, severe
drowsiness/dizziness) may be increased if this medication is used with other products that
may also cause drowsiness or breathing problems. Tell your doctor or pharmacist if you are
using other products such as other opioid pain or cough relievers (such as codeine,
hydrocodone), alcohol, marijuana (cannabis), drugs for sleep or anxiety (such as alprazolam,
lorazepam, zolpidem), muscle relaxants (such as carisoprodol, cyclobenzaprine), or
antihistamines (such as cetirizine, diphenhydramine).Check the labels on all your medicines
(such as allergy or cough-and-cold products) because they may contain ingredients that cause
drowsiness. Ask your pharmacist about using those products safely.This medication may
interfere with certain laboratory tests (including amylase and lipase levels), possibly causing
false test results. Make sure laboratory personnel and all your doctors know you use this drug.

OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or
trouble breathing, give them naloxone if available, then call 911. If the person is awake and
has no symptoms, call a poison control center right away. US residents can call their local
poison control center at 1-800-222-1222. Canada residents can call a provincial poison
control center. Symptoms of overdose may include: slow/shallow breathing, severe
drowsiness, slow heartbeat, severe dizziness, pinpoint pupils, coma.

NOTES: Do not share this medication with others. Sharing it is against the law.This
medication has been prescribed for your current condition only. Do not use it later for another
condition unless told to do so by your doctor. A different medication may be necessary in that
case.Ask your doctor or pharmacist if you should have naloxone available to treat opioid
overdose. Teach your family or household members about the signs of an opioid overdose
and how to treat it.

MISSED DOSE: If you use this medication regularly and miss a dose, use it as soon as you
remember. If it is near the time of the next dose, skip the missed dose. Use your next dose at
the regular time. Do not double the dose to catch up.

STORAGE: Store in the refrigerator between 36-46 degrees F (2-8 degrees C) away from
light. Do not store in the bathroom. Keep all medicines away from children and pets.Do not
flush medications down the toilet or pour them into a drain unless instructed to do so.
Properly discard this product when it is expired or no longer needed. Consult your pharmacist
or local waste disposal company for more details about how to safely discard your product.

Information last revised April 2019. Copyright(c) 2019 First Databank, Inc.

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT
have all possible information about this product. This information does not assure that this
product is safe, effective, or appropriate for you. This information is not individual medical
advice and does not substitute for the advice of your health care professional. Always ask
your health care professional for complete information about this product and your specific
health needs.