Exalgo (Hydromorphone Hydrochloride Extended Release Tablets)
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Exalgo (Hydromorphone Hydrochloride Extended Release Tablets)

EXALGO
(hydromorphone HCl) Extended Release Tablets

WARNING

ABUSE POTENTIAL, LIFE-THREATENING RESPIRATORY DEPRESSION, AND ACCIDENTAL EXPOSURE

Abuse Potential

EXALGO contains hydromorphone, an opioid agonist and a Schedule II controlled substance with an abuse liability similar to other opioid agonists, legal or illicit [see WARNINGS AND PRECAUTIONS]. Assess each patient's risk for opioid abuse or addiction prior to prescribing EXALGO. The risk for opioid abuse is increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depressive disorder). Routinely monitor all patients receiving EXALGO for signs of misuse, abuse, and addiction during treatment [see Drug Abuse and Dependence].

Life-threatening Respiratory Depression

Respiratory depression, including fatal cases, may occur with use of EXALGO, even when the drug has been used as recommended and not misused or abused [see WARNINGS AND PRECAUTIONS]. EXALGO is for use in opioid tolerant patients only. Proper dosing and titration are essential and EXALGO should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain. Monitor for respiratory depression, especially during initiation of EXALGO or following a dose increase. Crushing, dissolving, or chewing the tablet can cause rapid release and absorption of a potentially fatal dose of hydromorphone.

Accidental Exposure

Accidental ingestion of EXALGO, especially in children, can result in a fatal overdose of hydromorphone [see WARNINGS AND PRECAUTIONS].

DRUG DESCRIPTION

EXALGO tablets are for oral use and contain hydromorphone hydrochloride, a mu-opioid agonist.

Hydromorphone hydrochloride USP is 4,5α-epoxy-3-hydroxy-17-methlymorphinan-6-one hydrochloride. Hydromorphone hydrochloride is a white or almost white crystalline powder that is freely soluble in water, very slightly soluble in ethanol (96%), and practically insoluble in methylene chloride. Its empirical formula is C17H19NO3•HCl. The compound has the following structural formula:

EXALGO (hydromorphone HCl) Structural Formula Illustration

EXALGO also contains the following inactive ingredients: butylated hydroxytoluene, cellulose acetate, iron oxide black, ferric oxide red (8 mg only), ferric oxide yellow (12 mg and 16 mg only), hypromellose, lactose anhydrous, lactose monohydrate, magnesium stearate, polyethylene glycol, polyethylene oxide, povidone, sodium chloride, titanium dioxide, and triacetin.

What are the possible side effects of hydromorphone (Dilaudid, Dilaudid-5, Exalgo)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • shallow breathing, slow heartbeat;
  • seizure (convulsions);
  • cold, clammy skin;
  • confusion;
  • severe weakness or dizziness; or
  • feeling light-headed, fainting.

Less serious side effects are more likely to occur, such as:

  • nausea, vomiting, constipation, loss of...

Read All Potential Side Effects and See Pictures of Exalgo »

What are the precautions when taking hydromorphone hydrochloride extended release tablets (Exalgo)?

Before taking hydromorphone, tell your doctor or pharmacist if you are allergic to hydromorphone; or to other narcotic pain medications (such as morphine); or if you have any other allergies. This product may contain inactive ingredients (such as sulfites), 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: brain disorders (such as head injury, tumor, seizures), breathing problems (such as asthma, sleep apnea, chronic obstructive pulmonary disease-COPD), kidney disease, liver disease, mental/mood disorders (such as confusion, depression), personal or family history of regular use/abuse of drugs/alcohol, stomach/intestinal problems (such as...

Read All Potential Precautions of Exalgo »

Last reviewed on RxList: 7/23/2012
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

EXALGO is indicated for the management of moderate to severe pain in opioid tolerant patients requiring continuous, around-the-clock opioid analgesia for an extended period of time.

Patients considered opioid tolerant are those who are taking at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl/hour, 30 mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day or an equianalgesic dose of another opioid, for a week or longer.

Limitations of Use

EXALGO is not for use:

  • As an as-needed (prn) analgesic
  • For pain that is mild or not expected to persist for an extended period of time
  • For acute pain
  • For postoperative pain.

DOSAGE AND ADMINISTRATION

Initial Dosing

Initiate the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience. Overestimating the EXALGO dose when converting patients from another opioid medication can result in fatal overdose with the first dose. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with EXALGO [see WARNINGS AND PRECAUTIONS].

Consider the following factors when selecting an initial dose of EXALGO:

  • Total daily dose and potency of the opioid the patient has been taking previously;
  • Reliability of the relative potency estimate used to calculate the equivalent dose of hydromorphone needed (Note: potency estimates may vary with the route of administration);
  • Patient's degree of opioid experience and opioid tolerance;
  • General condition and medical status of the patient;
  • Concurrent medication;
  • Type and severity of the patient's pain.

EXALGO is administered at a frequency of once daily (every 24 hours), approximately the same time every day, with or without food.

To avoid medication errors, prescribers and pharmacists must be aware that hydromorphone is available as both immediate-release 8 mg tablets and extended-release 8 mg tablets.

Discontinue or taper all other extended-release opioids when beginning EXALGO therapy. As EXALGO is only for use in opioid-tolerant patients, do not begin any patient on EXALGO as the first opioid.

Conversion from Other Oral Hydromorphone Formulations to EXALGO

Patients receiving oral immediate-release hydromorphone may be converted to EXALGO by administering a starting dose equivalent to the patient's total daily oral hydromorphone dose, taken once daily.

Conversion from Oral Opioids to EXALGO

While there are useful tables of oral and parenteral equivalents, there is substantial inter-patient variation in the relative potency of different opioid drugs and formulations. Specific recommendations of equianalgesic doses are not available because of a lack of systematic evidence for these types of analgesic substitutions. Published relative potency data are available, but such ratios are approximations. As such, it is safer to underestimate a patient's 24-hour oral hydromorphone requirement and provide rescue medication (e.g. immediate-release hydromorphone) than to overestimate and manage an adverse reaction.

The following table was used in a clinical trial of EXALGO. The recommended starting dose of EXALGO is 50% of the calculated estimate of daily hydromorphone requirement. Calculate the estimated daily hydromorphone requirement using Table 1.

  • The conversion ratios in this Table 1 are only to be used for the conversion from current oral opioid therapy to EXALGO. Do not use this table to convert patients from EXALGO to another opioid. Doing so may result in fatal overdose.
  • For patients on a regimen of mixed opioids, calculate the approximate oral hydromorphone dose for each opioid and sum the totals.
  • For patients on a regimen of fixed-ratio opioid/non-opioid analgesic medications, only the opioid component of these medications should be used in the conversion.
  • It is extremely important to monitor all patients closely when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and tends to accumulate in the plasma.
  • Monitor patients for signs or symptoms of opioid withdrawal when converting patients to EXALGO.

Table 1: Conversion Ratios to EXALGO*

Previous Opioid Approximate Equivalent Oral Dose Approximate Oral Conversion Ratio
Hydromorphone 12 mg 1
Codeine 200 mg 0.06
Hydrocodone 30 mg 0.4
Methadone† 20 mg 0.6
Morphine 60 mg 0.2
Oxycodone 30 mg 0.4
Oxymorphone 20 mg 0.6
* The conversion ratios and approximate equivalent doses in this conversion table are only to be used for the conversion from current opioid therapy to EXALGO.
† It is extremely important to monitor all patients closely when converting from methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and tends to accumulate in the plasma.

Conversion from Transdermal Fentanyl to EXALGO

Eighteen hours following the removal of the transdermal fentanyl patch, EXALGO treatment can be initiated. For each 25 mcg/hr fentanyl transdermal dose, the equianalgesic dose of EXALGO is 12 mg every 24 hours. An appropriate starting dose of EXALGO is 50% of the calculated total daily dose every 24 hours.

Titration and Maintenance of Therapy

Individually titrate EXALGO to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving EXALGO to assess the maintenance of pain control and the relative incidence of adverse reactions. During chronic therapy, especially for non-cancer-related pain (or pain associated with other terminal illnesses), periodically reassess the continued need for the use of opioid analgesics.

If the level of pain increases, attempt to identify the source of increased pain, while adjusting the EXALGO dose to decrease the level of pain. Plasma levels of EXALGO are sustained for 18 to 24 hours. Dosage adjustments may be made every 3 to 4 days. Patients who experience breakthrough pain may require dosage adjustment or rescue medication.

If signs of excessive opioid-related adverse reactions are observed, the next dose may be reduced. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.

Discontinuation of EXALGO

When a patient no longer requires therapy with EXALGO, taper doses gradually, by 25 to 50% every 2 or 3 days down to a dose of 8 mg before discontinuation of therapy, to prevent signs and symptoms of withdrawal in the opioid-tolerant patient.

To dispose of unused EXALGO flush all remaining tablets down the toilet or remit to authorities at a certified drug take-back program.

Hepatic Impairment

Start patients with moderate hepatic impairment on 25% of the EXALGO dose that would be prescribed for 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. Use of alternate analgesics is recommended for patients with severe hepatic impairment [see Use in Specific Populations].

Renal Impairment

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 Use In Specific Populations].

Administration of EXALGO

Instruct patients to swallow EXALGO tablets intact. The tablets are not to be crushed, dissolved, or chewed due to the risk of rapid release and absorption of a potentially fatal dose of hydromorphone [see WARNINGS AND PRECAUTIONS].

HOW SUPPLIED

Dosage Forms And Strengths

EXALGO is available in 8 mg, 12 mg or 16 mg dosage strengths. The 8 mg tablets are round, biconvex, red tablets imprinted with “EXH 8” on one side. The 12 mg tablets are round, biconvex, dark yellow tablets imprinted with “EXH 12” on one side. The 16 mg tablets are round, biconvex, yellow tablets imprinted with “EXH 16” on one side.

Storage And Handling

EXALGO Tablet Strengths

Strength Color Tablet Description Bottle Count NDC
8 mg Red Round, biconvex, printed with “EXH 8” 100 23635-408-01
12 mg Dark yellow Round, biconvex, printed with “EXH 12” 100 23635-412-01
16 mg Yellow Round, biconvex, printed with “EXH 16” 100 23635-416-01

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].

Distributed by: Mallinckrodt Brand Pharmaceuticals, Inc., Hazelwood, MO 63042 USA, www.Exalgo.com or call 1-800-778-7898. Issue: July 2012

Last reviewed on RxList: 7/23/2012
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

The following serious adverse reactions are discussed elsewhere in the labeling:

  • Respiratory Depression [see WARNINGS AND PRECAUTIONS]
  • Chronic Pulmonary Disease [see WARNINGS AND PRECAUTIONS]
  • Head Injuries and Increased Intracranial Pressure [see WARNINGS AND PRECAUTIONS]
  • Interactions with Other CNS Depressants [see WARNINGS AND PRECAUTIONS]
  • Hypotensive Effect [see WARNINGS AND PRECAUTIONS]
  • Gastrointestinal Effects [see WARNINGS AND PRECAUTIONS]
  • Seizures [see WARNINGS AND PRECAUTIONS]

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

EXALGO was administered to a total of 2,524 patients in 15 controlled and uncontrolled clinical studies. Of these, 423 patients were exposed to EXALGO for greater than 6 months and 141 exposed for greater than one year.

The most common adverse reactions leading to study discontinuation were nausea, vomiting, constipation, somnolence, and dizziness. The most common treatment-related serious adverse reactions from controlled and uncontrolled chronic pain studies were drug withdrawal syndrome, overdose, confusional state, and constipation.

The overall incidence of adverse reactions in patients greater than 65 years of age was higher, with a greater than 5% difference in rates for constipation and nausea when compared with younger patients. The overall incidence of adverse reactions in female patients was higher, with a greater than 5% difference in rates for nausea, vomiting, constipation and somnolence when compared with male patients.

A 12-week double-blind, placebo-controlled, randomized withdrawal study was conducted in opioid tolerant patients with moderate to severe low back pain [see Clinical Studies]. A total of 447 patients were enrolled into the open-label titration phase with 268 patients randomized into the double-blind treatment phase. The adverse reactions that were reported in at least 2% of the patients are contained in Table 2.

Table 2: Number (%) of Patients with Adverse Reactions Reported in ≥ 2% of Patients with Moderate to Severe Low Back Pain During the Open-Label Titration Phase or Double-Blind Treatment Phase by Preferred Term

Preferred Term Open-Label Titration Phase Double-Blind Treatment Phase
EXALGO
(N=447)
EXALGO
(N=134)
Placebo
(N=134)
Constipation 69 (15) 10 (7) 5 (4)
Nausea 53 (12) 12 (9) 10 (7)
Somnolence 39 (9) 1 (1) 0 (0)
Headache 35 (8) 7 (5) 10 (7)
Vomiting 29 (6) 8 (6) 6 (4)
Drug Withdrawal Syndrome 22 (5) 13 (10) 16 (12)
Pruritus 21 (5) 1 (1) 0 (0)
Dizziness 17 (4) 3 (2) 2 (1)
Asthenia/Fatigue 16 (4) 2 (1) 6 (4)
Insomnia 13 (3) 7 (5) 5 (4)
Diarrhea 13 (3) 5 (4) 9 (7)
Back Pain 13 (3) 6 (4) 8 (6)
Dry Mouth 13 (3) 2 (1) 0 (0)
Edema Peripheral 13 (3) 3 (2) 1 (1)
Hyperhidrosis 13 (3) 2 (1) 2 (1)
Anorexia/Decreased Appetite 10 (2) 2 (1) 0 (0)
Arthralgia 9 (2) 8 (6) 3 (2)
Anxiety 9 (2) 0 (0) 4 (3)
Abdominal Pain 9 (2) 4 (3) 3 (2)
Muscle Spasms 5 (1) 3 (2) 1 (1)
Weight Decreased 3 (1) 4 (3) 3 (2)

The adverse reactions that were reported in at least 2% of the total treated patients (N=2,474) in the 14 chronic clinical trials are contained in Table 3.

Table 3: Number (%) of Patients with Adverse Reactions Reported in ≥ 2% of Patients with Chronic Pain Receiving EXALGO in 14 Clinical Studies by Preferred Term

Preferred Term All Patients
(N=2,474)
Constipation 765 (31)
Nausea 684 (28)
Vomiting 337 (14)
Somnolence 367 (15)
Headache 308 (12)
Asthenia/Fatigue 272 (11)
Dizziness 262 (11)
Diarrhea 201 (8)
Pruritus 193 (8)
Insomnia 161 (7)
Hyperhidrosis 143 (6)
Edema Peripheral 135 (5)
Anorexia/Decreased Appetite 139 (6)
Dry Mouth 121 (5)
Abdominal Pain 115 (5)
Anxiety 95 (4)
Back Pain 95 (4)
Dyspepsia* 88 (4)
Depression 81 (3)
Dyspnea 76 (3)
Muscle Spasms 74 (3)
Arthralgia 72 (3)
Rash 64 (3)
Pain in Extremity 63 (3)
Pain 58 (2)
Drug Withdrawal Syndrome 55 (2)
Pyrexia 52 (2)
Fall 51 (2)
Chest pain 51 (2)
* Reflux esophagitis, gastroesophageal reflux disease and Barrett's esophagus were grouped and reported with dyspepsia

The following Adverse Reactions occurred in patients with an overall frequency of < 2% and are listed in descending order within each System Organ Class:

Cardiac disorders: palpitations, tachycardia, bradycardia, extrasystoles

Ear and labyrinth disorders: vertigo, tinnitus

Endocrine disorders: hypogonadism

Eye disorders: vision blurred, diplopia, dry eye, miosis

Gastrointestinal disorders: flatulence, dysphagia, hematochezia, abdominal distension, hemorrhoids, abnormal feces, intestinal obstruction, eructation, diverticulum, gastrointestinal motility disorder, large intestine perforation, anal fissure, bezoar, duodenitis, ileus, impaired gastric emptying, painful defecation

General disorders and administration site conditions: chills, malaise, feeling abnormal, feeling hot and cold, feeling jittery, hangover, difficulty in walking, feeling drunk, hypothermia

Infections and infestations: gastroenteritis, diverticulitis

Injury, poisoning and procedural complications: contusion, overdose

Investigations: weight decreased, hepatic enzyme increased, blood potassium decreased, blood amylase increased, blood testosterone decreased, oxygen saturation decreased

Metabolism and nutrition disorders: dehydration, fluid retention, increased appetite, hyperuricemia

Musculoskeletal and connective tissue disorders: myalgia

Nervous system disorders: tremor, sedation, hypoesthesia, paresthesia, disturbance in attention, memory impairment, dysarthria, syncope, balance disorder, dysgeusia, depressed level of consciousness, coordination abnormal, hyperesthesia, myoclonus, dyskinesia, hyperreflexia, encephalopathy, cognitive disorder, convulsion, psychomotor hyperactivity

Psychiatric disorders: confusional state, nervousness, restlessness, abnormal dreams, mood altered, hallucination, panic attack, euphoric mood, paranoia, dysphoria, listless, crying, suicide ideation, libido decreased, aggression

Renal and urinary disorders: dysuria, urinary retention, urinary frequency, urinary hesitation, micturition disorder

Reproductive system and breast disorders: erectile dysfunction, sexual dysfunction

Respiratory, thoracic and mediastinal disorders: rhinorrhea, respiratory distress, hypoxia, bronchospasm, sneezing, hyperventilation, respiratory depression

Skin and subcutaneous tissue disorders: erythema Vascular disorders: flushing, hypertension, hypotension

Read the Exalgo (hydromorphone hydrochloride extended release tablets) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

CNS Depressants

Avoid use of EXALGO with central nervous system depressants such as hypnotics, sedatives, general anesthetics, antipsychotics and alcohol, due to the increased risk of respiratory depression, hypotension and profound sedation or coma.

Mixed Agonist/Antagonist Opioid Analgesics

Mixed agonist/antagonists (buprenorphine, nalbuphine, pentazocine) may reduce the analgesic effect of EXALGO and/or may precipitate withdrawal symptoms in these patients. Avoid the use of agonist/antagonist analgesics in patients receiving EXALGO.

Monoamine Oxidase Inhibitors (MAOI)

The effects of opioid analgesics may be potentiated by MAOIs. EXALGO is not recommended for use in patients who have received MAOIs within 14 days. If concurrent therapy with an MAOI and EXALGO is unavoidable, monitor patients for increased respiratory and central nervous system depression.

Anticholinergics

Anticholinergics or other medications with anticholinergic activity when used concurrently with EXALGO may result in increased risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor patients for signs of urinary retention or reduced gastric motility when EXALGO is used concurrently with anticholinergic drugs.

Drug Abuse And Dependence

Controlled Substance

EXALGO contains hydromorphone, a Schedule II controlled substance with a high potential for abuse similar to fentanyl, methadone, morphine, oxycodone, and oxymorphone. EXALGO can be abused and is subject to misuse, abuse, addiction, and criminal diversion [see WARNINGS AND PRECAUTIONS]. The high drug content in the extended release formulation adds to the risk of adverse outcomes from abuse and misuse.

Abuse

All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use.

Drug abuse is the intentional non-therapeutic use of an over-the-counter or prescription drug, even once, for its rewarding psychological or physiological effects. Drug abuse includes, but is not limited to the following examples: the use of a prescription or over-the-counter drug to get “high”, or the use of steroids for performance enhancement and muscle build up.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and include: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.

“Drug-seeking” behavior is very common to addicts and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated claims of loss of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” (visiting multiple prescribers) to obtain additional prescriptions is common among drug abusers, people suffering from untreated addiction and criminals seeking drugs to sell.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances.

EXALGO can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by law, is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Risks Specific to Abuse of EXALGO

EXALGO is intended for oral use only. Abuse of EXALGO poses a risk of overdose and death. This risk is increased with concurrent abuse of EXALGO with alcohol and other substances.

Taking cut, broken, chewed, crushed, or dissolved EXALGO poses a hazard of overdose and death.

With intravenous abuse, the tablet excipients, especially polyethylene oxide, can be expected to result in necrosis and inflammation of cardiac tissues. In addition, parenteral drug abuse is commonly associated with transmission of infectious disease such as hepatitis and HIV.

Healthcare professionals should contact their State Professional Licensing Board or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.

Dependence

Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dose reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity, e.g., naloxone, nalmefene, or mixed agonist/antagonist analgesics (pentazocine, butorphanol, buprenorphine, nalbuphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.

EXALGO should not be abruptly discontinued [see DOSAGE AND ADMINISTRATION]. If EXALGO is abruptly discontinued in a physically-dependent patient, an abstinence syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, piloerection, myalgia, mydriasis, irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, increased blood pressure, respiratory rate, or heart rate.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal symptoms [see Use In Specific Populations].

Last reviewed on RxList: 7/23/2012
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Abuse Potential

EXALGO contains hydromorphone, an opioid agonist and a Schedule II controlled substance. Hydromorphone can be abused in a manner similar to other opioid agonists, legal or illicit. Opioid agonists are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing EXALGO in situations where there is concern about increased risks of misuse, abuse, or diversion. Concerns about abuse, addiction, and diversion should not, however, prevent the proper management of pain.

Assess each patient's risk for opioid abuse or addiction prior to prescribing EXALGO. The risk for opioid abuse is increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression). Patients at increased risk may still be appropriately treated with modified-release opioid formulations; however these patients will require intensive monitoring for signs of misuse, abuse, or addiction. Routinely monitor all patients receiving opioids for signs of misuse, abuse, and addiction because these drugs carry a risk for addiction even under appropriate medical use.

Misuse or abuse of EXALGO by crushing, chewing, snorting, or injecting the dissolved product will result in the uncontrolled delivery of the opioid and pose a significant risk that could result in overdose and death [see OVERDOSAGE].

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

Respiratory depression is the primary risk of EXALGO. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Respiratory depression from opioids is manifested by a reduced urge to breathe and a decreased rate of respiration, often associated with a “sighing” pattern of breathing (deep breaths separated by abnormally long pauses). Carbon dioxide (CO2) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient's clinical status [see OVERDOSAGE].

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 dose increase. Closely monitor patients for respiratory depression when initiating therapy with EXALGO and following dose increases. Instruct patients against use by individuals other than the patient for whom EXALGO was prescribed and to keep EXALGO out of the reach of children, as such inappropriate use may result in fatal respiratory depression.

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. Respiratory depression has also been reported with use of modified-release opioids when used as recommended and not misused or abused.

To further reduce the risk of respiratory depression, consider the following:

  • Proper dosing and titration are essential and EXALGO should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.
  • EXALGO is for use in opioid-tolerant patients only. Ingestion of EXALGO may cause fatal respiratory depression when administered to patients not already tolerant to opioids.
  • Instruct patients to swallow EXALGO tablets intact. The tablets are not to be crushed, dissolved, or chewed. The resulting hydromorphone dose may be fatal.
  • EXALGO is contraindicated in patients with respiratory depression and in patients with conditions that increase the risk of life-threatening respiratory depression [see CONTRAINDICATIONS].

Accidental Exposure

Accidental ingestion of EXALGO, especially in children, can result in a fatal overdose of hydromorphone.

Elderly, Cachectic, and Debilitated Patients

Respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients as they may have altered pharmacokinetics due to poor fat stores, muscle wasting, or altered clearance compared to younger, healthier patients. Therefore, monitor such patients closely, particularly when initiating and titrating EXALGO and when EXALGO is given concomitantly with other drugs that depress respiration.

Use in Patients with Chronic Pulmonary Disease

Monitor patients with significant chronic obstructive pulmonary disease or cor pulmonale, and patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression for respiratory depression, particularly when initiating therapy and titrating with EXALGO, as in these patients, even usual therapeutic doses of EXALGO may decrease respiratory drive to the point of apnea. Consider the use of alternative non-opioid analgesics in these patients if possible.

Interactions with Alcohol, Other CNS Depressants, and Illicit Drugs

Hypotension, profound sedation, coma, or respiratory depression may result if EXALGO is used concomitantly with other CNS depressants (e.g., sedatives, anxiolytics, hypnotics, neuroleptics, other opioids). When considering the use of EXALGO in a patient taking a CNS depressant, assess the duration of use of the CNS depressant and the patient's response, including the degree of tolerance that has developed to CNS depression. Additionally, consider the patient's use, if any, of alcohol or illicit drugs that cause CNS depression. If EXALGO therapy is to be initiated in a patient taking a CNS depressant, start with a lower EXALGO dose than usual and monitor patients for signs of sedation and respiratory depression and consider using a lower dose of the concomitant CNS depressant [see DRUG INTERACTIONS].

Hypotensive Effect

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 dose of EXALGO.

Use in Patients with Head Injury or Increased Intracranial Pressure

Monitor patients taking EXALGO who may be susceptible to the intracranial effects of CO2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors) for signs of sedation and respiratory depression, particularly when initiating therapy with EXALGO. EXALGO may reduce respiratory drive, and the resultant CO2 retention can further increase intracranial pressure. 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.

Use in Patients with Gastrointestinal Conditions

EXALGO is contraindicated in patients with 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. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.

Sulfites

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.

Use in Patients with Convulsive or Seizure Disorders

The hydromorphone in EXALGO may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings. Monitor patients with a history of seizure disorders for worsened seizure control during EXALGO therapy.

Avoidance of Withdrawal

Avoid the use of mixed agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and butorphanol) in patients who have received or are receiving a course of therapy with a full opioid agonist analgesic, including EXALGO. In these patients, mixed agonists/antagonists 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.

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.

Patient Counseling Information

See FDA-approved patient labeling (Medication Guide)

Abuse Potential

Inform patients that EXALGO contains hydromorphone, a Schedule II controlled substance that is subject to abuse. Instruct patients not to share EXALGO with others and to take steps to protect EXALGO from theft or misuse.

Life-threatening Respiratory Depression

Discuss the risk of respiratory depression with patients, explaining that the risk is greatest when starting EXALGO or when the dose is increased. Advise patients how to recognize respiratory depression and to seek medical attention if they are experiencing breathing difficulties.

Accidental Exposure

Instruct patients to take steps to store EXALGO securely. Accidental exposure, especially in children, may result in serious harm or death. Advise patients to dispose of unused EXALGO by flushing the tablets down the toilet or remit to authorities at a certified drug take-back program.

Risks from Concomitant Use of Alcohol and other CNS Depressants

Inform patients that the concomitant use of alcohol with EXALGO can increase the risk of life-threatening respiratory depression. Instruct patients not to consume alcoholic beverages, as well as prescription and over-the-counter drug products that contain alcohol, during treatment with EXALGO.

Inform patients that potentially serious additive effects may occur if EXALGO is used with other CNS depressants, and not to use such drugs unless supervised by a health care provider.

Important Administration Instructions

Instruct patients how to properly take EXALGO, including the following:

  • Swallowing EXALGO whole
  • Not crushing, chewing, splitting or dissolving the tablets
  • Using EXALGO exactly as prescribed to reduce the risk of life-threatening adverse reactions (e.g., respiratory depression)
  • Not discontinuing EXALGO without first discussing the need for a tapering regimen with the prescriber
Gastrointestinal Blockage

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.

Hypotension

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).

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.

Constipation

Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention.

Anaphylaxis

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.

Pregnancy

Advise female patients that EXALGO can cause fetal harm and to inform the prescriber if they are pregnant or plan to become pregnant.

Disposal

Advise patients that when EXALGO is no longer needed to flush the unused tablets down the toilet or remit to authorities at a certified drug take-back program.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Long-term studies in animals to evaluate the carcinogenic potential of hydromorphone hydrochloride have not been conducted.

Mutagenesis

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

Hydromorphone given orally to rats during the mating period caused a slight but statistically significant reduction in implantations at 6.25 mg/kg/day (~1.2 times the human exposure following to 32 mg/day).

Use In Specific Populations

Pregnancy

Teratogenic Effects

Pregnancy Category C: There are no adequate and well-controlled studies in pregnant women. Hydromorphone crosses the placenta. EXALGO should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Hydromorphone was not teratogenic in pregnant rats given oral doses up to 6.25 mg/kg/day or in pregnant rabbits administered oral doses up to 25 mg/kg/day during the period of organogenesis (~1.2 times the human exposure following 32 mg/day).

Hydromorphone administration to pregnant Syrian hamsters and CF-1 mice during major organ development revealed teratogenicity likely the result of maternal toxicity associated with sedation and hypoxia. In Syrian hamsters given single subcutaneous doses from 14 to 258 mg/kg during organogenesis (gestation days 8 to 10), doses ≥ 19 mg/kg hydromorphone produced skull malformations (exencephaly and cranioschisis). Continuous infusion of hydromorphone (5 mg/kg, s.c.) via implanted osmotic mini pumps during organogenesis (gestation days 7 to 10) produced soft tissue malformations (cryptorchidism, cleft palate, malformed ventricals and retina), and skeletal variations (supraoccipital, checkerboard and split sternebrae, delayed ossification of the paws and ectopic ossification sites). The malformations and variations observed in the hamsters and mice were at doses approximately three-fold higher and < one-fold lower, respectively, than a 32 mg human daily oral dose on a body surface area basis.

Nonteratogenic Effects

In the pre- and post-natal effects study in rats, neonatal viability was reduced at 6.25 mg/kg/day (~1.2 times the human exposure following 32 mg/day).

Neonates born to mothers who have been taking opioids regularly prior to delivery will be physically dependent. The withdrawal signs include irritability and excessive crying, tremors, hyperactive reflexes, increased respiratory rate, increased stools, sneezing, yawning, vomiting, and fever. The intensity of the syndrome does not always correlate with the duration of maternal opioid use or dose. There is no consensus on the best method of managing withdrawal. Approaches to the treatment of the syndrome have included supportive care and, if indicated, drugs such as paregoric or phenobarbital.

Labor and Delivery

EXALGO is not for use in women during and immediately prior to labor, where shorter acting analgesics or other analgesic techniques are more appropriate [see INDICATIONS AND USAGE]. Occasionally, opioid analgesics may prolong labor by temporarily reducing the strength, duration, and frequency of uterine contractions. However, these effects are not consistent and may be offset by an increased rate of cervical dilatation which tends to shorten labor.

Opioids cross the placenta and may produce respiratory depression and psychophysiologic effects in neonates. Closely observe neonates whose mothers received opioid analgesics during labor for signs of respiratory depression. An opioid antagonist, such as naloxone, should be available for reversal of opioid-induced respiratory depression in the neonate in such situations.

Nursing Mothers

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.

Pediatric Use

The safety and effectiveness of EXALGO in patients 17 years of age and younger have not been established.

Geriatric Use

Elderly patients have been shown to be more sensitive to the adverse effects of opioids compared to the younger population. Therefore, closely monitor elderly patients for respiratory and central nervous system depression when prescribing EXALGO, particularly during initiation and titration.

Neonatal Opioid Withdrawal Syndrome

Chronic maternal use of hydromorphone during pregnancy can affect the neonate with subsequent withdrawal signs. Neonatal 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 withdrawal syndrome vary based on the drug used, duration of use, the dose of last maternal use, and rate of elimination drug by the newborn. Neonatal opioid withdrawal syndrome may be life-threatening and should be treated according to protocols developed by neonatology experts.

Hepatic Impairment

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 is expected, use of alternate analgesics is recommended [see DOSAGE AND ADMINISTRATION].

Renal Impairment

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 (40 hours) compared to subjects with normal renal function (15 hours). 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].

Last reviewed on RxList: 7/23/2012
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

Clinical Presentation

Acute overdosage with opioids can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and sometimes pulmonary edema, bradycardia, hypotension and death. Marked mydriasis rather than miosis may be seen due to severe hypoxia in overdose situations.

Treatment of Overdose

Due to the delayed mean apparent peak plasma level of EXALGO occurring at 16 hours following administration as well as the 11 hour mean elimination half-life of EXALGO, patients who receive an overdose will require an extended period of monitoring and treatment that may go beyond 24 to 48 hours.

In case of overdose, priorities are the re-establishment of a patent and protected airway and institution of assisted or controlled ventilation if needed. Employ other supportive measures (including oxygen, vasopressors) in the management of circulatory shock and pulmonary edema as indicated. Cardiac arrest or arrhythmias will require advanced life support techniques.

The opioid antagonists, such as naloxone and naltrexone, are specific antidotes to respiratory depression resulting from opioid overdose. Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to hydromorphone overdose. Such agents should be administered cautiously to patients who are known, or suspected to be, physically dependent on EXALGO. In such cases, an abrupt or complete reversal of opioid effects may precipitate an acute withdrawal syndrome.

Because the duration of reversal would be expected to be less than the duration of action of hydromorphone in EXALGO, carefully monitor the patient until spontaneous respiration is reliably reestablished. EXALGO will continue to release hydromorphone adding to the hydromorphone load for up to 24 hours after administration, necessitating prolonged monitoring for at least 24 to 48 hours beyond the overdose. If the response to opioid antagonists is suboptimal or not sustained, additional antagonist should be given as directed in the product's prescribing information.

In an individual physically dependent on opioids, administration of an opioid receptor antagonist may precipitate an acute withdrawal. The severity of the withdrawal syndrome produced will depend on the degree of physical dependence and the dose of the antagonist administered. If a decision is made to treat serious respiratory depression in the physically dependent patient, administration of the antagonist should be begun with care and by titration with smaller than usual doses of the antagonist.

CONTRAINDICATIONS

EXALGO is contraindicated in:

  • Opioid non-tolerant patients. Fatal respiratory depression could occur in patients who are not opioid tolerant.
  • Patients with significant respiratory depression
  • Patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment
  • Patients with known or suspected paralytic ileus
  • Patients who have had surgical procedures and/or underlying disease resulting in narrowing of the gastrointestinal tract, or have “blind loops” of the gastrointestinal tract or gastrointestinal obstruction.
  • Patients with hypersensitivity (e.g., anaphylaxis) to hydromorphone or sulfite-containing medications [see WARNINGS AND PRECAUTIONS]

Last reviewed on RxList: 7/23/2012
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Hydromorphone, a semi-synthetic morphine derivative, is a hydrogenated ketone of morphine. Hydromorphone is principally an agonist of mu-receptors, showing a weak affinity for κ-receptors. Comparing relative binding affinity for mu- and κ-opioid receptors, hydromorphone binds more specifically to mu-receptors than structurally related morphine. As an opioid agonist, the principle therapeutic action of hydromorphone is analgesia. The precise mechanism of action of opioid analgesics is not known but the effects are thought to be mediated through opioid-specific receptors located predominantly in the central nervous system (CNS). Interaction with the mu-opioid receptor subtype is believed to be responsible for most of hydromorphone's clinical effects. There is no intrinsic limit to the analgesic effect of hydromorphone. Clinically, however, dosage limitations are imposed by the adverse effects, primarily respiratory depression, sedation, nausea, and vomiting, which can result from high doses.

Effects on the Central Nervous System

Hydromorphone produces dose-related respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the responsiveness of the brain stem respiratory centers to increases in carbon dioxide tension and to electrical stimulation.

Hydromorphone depresses the cough reflex by direct effect on the cough center in the medulla.

Hydromorphone causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomic. Marked mydriasis, rather than miosis, may be seen due to severe hypoxia in overdose situations.

Effects on the Gastrointestinal Tract and Other Smooth Muscle

Gastric, biliary and pancreatic secretions are decreased by hydromorphone. Hydromorphone causes a reduction in motility associated with an increase in tone in the antrum of the stomach and duodenum. Digestion of food in the small intestine is delayed and propulsive contractions are decreased. Propulsive peristaltic waves in the colon are decreased, while tone may be increased to the point of spasm. The end result is constipation. Hydromorphone also can cause an increase in biliary tract pressure as a result of spasm of the sphincter of Oddi.

Effects on the Cardiovascular System

Hydromorphone produces peripheral vasodilation which may result in orthostatic hypotension or syncope. Release of histamine may be induced by hydromorphone and can contribute to opioid-induced hypotension. Manifestations of histamine release or peripheral vasodilation may include pruritus, flushing, red eyes, and sweating.

Effects on the Endocrine System

Opioids inhibit the secretion of ACTH, cortisol, and luteinizing hormone (LH) in humans. They also stimulate prolactin, growth hormone (GH) secretion, and pancreatic secretion of insulin and glucagon.

Effects on the Immune System

Opioids have been shown to have a variety of effects on components of the immune system in in vitro and animal models. The clinical significance of these findings is unknown. Overall, the effects of opioids appear to be modestly immunosuppressive.

Pharmacodynamics

CNS Depressant/Alcohol Interaction

Additive pharmacodynamic effects may be expected when EXALGO is used in conjunction with alcohol, other opioids, legal or illicit drugs that cause central nervous system depression.

Pharmacokinetics

Absorption

EXALGO is an extended-release formulation of hydromorphone that produces a gradual increase in hydromorphone concentrations. Following a single-dose administration of EXALGO, plasma concentrations gradually increase over 6 to 8 hours, and thereafter concentrations are sustained for approximately 18 to 24 hours post-dose. The median Tmax values ranged from 12 to 16 hours. The mean half-life was approximately 11 hours, ranging from 8 to 15 hours in most individual subjects. Linear pharmacokinetics has been demonstrated for EXALGO over the dose range 8 to 64 mg, with a dose-proportional increase in Cmax and overall exposure (AUC0-∞) (see Table 4). Steady-state plasma concentrations are approximately twice those observed following the first dose, and steady state is reached after 3 to 4 days of once-daily dosing of EXALGO. At steady state, EXALGO given once daily maintained hydromorphone plasma concentrations within the same concentration range as the immediate-release tablet given 4 times daily at the same total daily dose and diminished the fluctuations between peak and trough concentrations seen with the immediate-release tablet (see Figure 1). The bioavailability of EXALGO once daily and immediate-release hydromorphone four times daily in adults is comparable, as presented in Table 4.

Figure 1: Mean Steady-State Plasma Concentration Profile

Mean Steady-State Plasma Concentration Profile - Illustration

Table 4: Mean (±SD) EXALGO Pharmacokinetic Parameters

Regimen Dosage Tmax* (hrs) Cmax (ng/mL) AUC (ng•hr/mL) T½ (hr)
Single Dose
(N = 31)
8 mg 12 (4-30) 0.93 (1.01) 18.1 (5.8) 10.6 (4.3)
16 mg 16 (6-30) 1.69 (0.78) 36.5 (11.3) 10.3 (2.4)
32 mg 16 (4-24) 3.25 (1.37) 72.2 (24.3) 11.0 (3.2)
64 mg 16 (6-30) 6.61 (1.75) 156.0 (30.6) 10.9 (3.8)
Multiple Dose†
(N = 29)
16 mg q24h 12 (6-24) 3.54 (0.96)‡ 57.6 (16.3) NA
IR 4 mg q6h 0.75 (0.5-2) 5.28 (1.37)§ 54.8 (14.8) NA
NA = not applicable
* Median (range) reported for Tmax
† Steady-state results on Day 5 (0-24 hours)
‡ Cmin 2.15 (0.87) ng/mL
§ Cmin 1.47 (0.42) ng/mL

Food Effect

The pharmacokinetics of EXALGO are not affected by food as indicated by bioequivalence when administered under fed and fasting conditions. Therefore, EXALGO may be administered without regard to meals. When a 16 mg dose of EXALGO was administered to healthy volunteers immediately following a high-fat meal, the median time to Cmax (Tmax) was minimally affected by the high-fat meal occurring at 16 hours compared to 18 hours while fasting.

Distribution

Following intravenous administration of hydromorphone to healthy volunteers, the mean volume of distribution was 2.9 (±1.3) L/kg, suggesting extensive tissue distribution. The mean extent of binding of hydromorphone to human plasma proteins was determined to be 27% in an in vitro study.

Metabolism

After oral administration of an immediate-release formulation, hydromorphone undergoes extensive first-pass metabolism and is metabolized primarily in the liver by glucuronidation to hydromorphone-3glucuronide, which follows a similar time course to hydromorphone in plasma. Exposure to the glucuronide metabolite is 35 to 40 times higher than exposure to the parent drug. In vitro data suggest that hydromorphone in clinically relevant concentrations has minimal potential to inhibit the activity of human hepatic CYP450 enzymes including CYP1A2, 2C9, 2C19, 2D6, 3A4, and 4A11.

Excretion

Approximately 75% of the administered dose is excreted in urine. Most of the administered hydromorphone dose is excreted as metabolites. Approximately 7% and 1% of the dose are excreted as unchanged hydromorphone in urine and feces, respectively.

Special Populations

Geriatric Patients

Based on data obtained from a study using immediate-release hydromorphone, the pharmacokinetics of hydromorphone in healthy elderly subjects (65 to 74 years old) are similar to the pharmacokinetics in healthy young subjects.

Pediatric Patients

The pharmacokinetics of EXALGO were not evaluated in a pediatric population.

Gender

Females appeared to have approximately 10% higher mean systemic exposure in terms of Cmax and AUC values.

Race

The effect of race on EXALGO pharmacokinetics has not been studied.

Hepatic Impairment

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). Pharmacokinetics of hydromorphone in severe hepatic impairment patients has not been studied. Further increase in Cmax and AUC0-∞ of hydromorphone in this group is expected. Start patients with moderate hepatic impairment on 25% of the usual dose of EXALGO and closely monitor for respiratory and central nervous system depression during dose titration. Consider alternate analgesic therapy for patients with severe hepatic impairment [see DOSAGE AND ADMINISTRATION and Use In Specific Populations].

Renal Impairment

Renal impairment affected the pharmacokinetics of hydromorphone and its metabolites following administration of a single 4 mg dose of immediate-release tablets. The effects of renal impairment on hydromorphone pharmacokinetics were 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 (40 hr) compared to subjects with normal renal function (15 hr). Start patients with moderate renal impairment on 50% of the usual EXALGO dose for patients with normal renal function and closely monitor for respiratory and central nervous system depression 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 and Use In Specific Populations].

Drug Interaction/Alcohol Interaction

An in vivo study examined the effect of alcohol (40%, 20%, 4% and 0%) on the bioavailability of a single dose of 16 mg of EXALGO in healthy, fasted or fed volunteers. The results showed that the hydromorphone mean AUC0-∞ was 5% higher and 4% lower (not statistically significant) in the fasted and fed groups respectively after co-administration of 240 mL of 40% alcohol. The AUC0-∞ was similarly unaffected in subjects following the co-administration of EXALGO and alcohol (240 mL of 20% or 4% alcohol).

The change in geometric mean Cmax with concomitant administration of alcohol and EXALGO ranged from an increase of 10% to 31% across all conditions studied. The change in mean Cmax was greater in the fasted group of subjects. Following concomitant administration of 240 mL of 40% alcohol while fasting, the mean Cmax increased by 37% and up to 151% in an individual subject. Following the concomitant administration of 240 mL of 20% alcohol while fasting, the mean Cmax increased by 35% and up to 139% in an individual subject. Following the concomitant administration of 240 mL of 4% alcohol while fasting, the mean Cmax increased by 19% on average and as much as 73% for an individual subject. The range of median Tmax for the fed and fasted treatments with 4%, 20% and 40% alcohol was 12 to 16 hours compared to 16 hours for the 0% alcohol treatments.

Clinical Studies

EXALGO was investigated in a double-blind, placebo-controlled, randomized withdrawal study in opioid tolerant patients with moderate-to-severe low back pain. Patients were considered opioid tolerant if they were currently on opioid therapy that was ≥ 60 mg/day of oral morphine equivalent for at least 2 months prior to screening. Patients entered an open-label conversion and titration phase with EXALGO, were converted to a starting dose that was approximately 75% of their total daily morphine equivalent dose, and were dosed once daily until adequate pain control was achieved while exhibiting tolerable side effects. Supplemental immediate-release hydromorphone tablets were allowed throughout the study. Patients who achieved a stable dose entered a 12-week, double-blind, placebo-controlled, randomized treatment phase. Mean daily dose at randomization was 37.8 mg/day (range of 12 mg/day to 64 mg/day). Fifty-eight (58) percent of patients were successfully titrated to a stable dose of EXALGO during the open-label conversion and titration phase.

During the double-blind treatment phase, patients randomized to EXALGO continued with the stable dose achieved in the conversion and titration phase of the study. Patients randomized to placebo received, in a blinded manner, EXALGO and matching placebo in doses tapering from the stable dose achieved in conversion and titration. During the taper down period, patients were allowed immediate-release hydromorphone tablets as supplemental analgesia to minimize opioid withdrawal symptoms in placebo patients. After the taper period, the number of immediate-release hydromorphone tablets was limited to two tablets per day. Forty-nine (49) percent of patients treated with EXALGO and 33% of patients treated with placebo completed the 12-week treatment period.

EXALGO provided superior analgesia compared to placebo. There was a significant difference between the mean changes from Baseline to Week 12 or Final Visit in average weekly pain intensity Numeric Rating Scale (NRS) scores obtained from patient diaries between the two groups. The proportion of patients with various degrees of improvement from screening to Week 12 or Final Visit is shown in Figure 2. For this analysis, patients who discontinued treatment for any reason prior to Week 12 were assigned a value of zero improvement.

Figure 2: Percent Reduction in Average Pain Intensity from Screening to Week 12 or Final Visit

Percent Reduction in Average Pain Intensity - Illustration

Last reviewed on RxList: 7/23/2012
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Medication Guide

EXALGO®
(eks-al-goh)
(hydromorphone hydrochloride) Extended-Release Tablets

EXALGO is:

  • A strong prescription pain medicine that contains an opioid (narcotic) that is used to treat moderate to severe around-the-clock pain, in people who are already regularly using opioid pain medicine.

Important information about EXALGO:

  • Get emergency help right away if you take too much EXALGO (overdose). EXALGO overdose can cause life threatening breathing problems that can lead to death.
  • Never give anyone else your EXALGO. They could die from taking it. Store EXALGO away from children and in a safe place to prevent stealing or abuse. Selling or giving away EXALGO is against the law.

Do not take EXALGO if you have:

  • severe asthma, trouble breathing, or other lung problems.
  • a bowel blockage or have narrowing of the stomach or intestines.

Before taking EXALGO, tell your healthcare provider if you have a history of:

  • head injury, seizures
  • liver, kidney, thyroid problems
  • allergy to hydromorphone or sulfites
  • problems urinating
  • pancreas or gallbladder problems
  • abuse of street or prescription drugs, alcohol addiction, or mental health problems.

Tell your healthcare provider if you are:

  • pregnant or planning to become pregnant. EXALGO may harm your unborn baby.
  • breastfeeding. EXALGO passes into breast milk and may harm your baby.
  • taking prescription or over-the-counter medicines, vitamins, or herbal supplements.

When taking EXALGO:

  • Do not change your dose. Take EXALGO exactly as prescribed by your healthcare provider.
  • Take your prescribed dose at the same time every day. Do not take more than your prescribed dose in 24 hours. If you miss a dose, do not take EXALGO. Take your next dose at your usual time the next day.
  • Swallow EXALGO whole. Do not cut, break, chew, crush, dissolve, or inject EXALGO.
  • Call your healthcare provider if the dose you are taking does not control your pain.
  • Do not stop taking EXALGO without talking to your healthcare provider.
  • EXALGO is contained in a hard tablet shell that you may see in your bowel movement; this is normal.
  • After you stop taking EXALGO, flush any unused tablets down the toilet.

While taking EXALGO Do Not:

  • Drive or operate heavy machinery, until you know how EXALGO affects you. EXALGO can make you sleepy, dizzy, or lightheaded.
  • Drink alcohol or use prescription or over-the-counter medicines that contain alcohol.

The possible side effects of EXALGO are:

  • constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness. Call your healthcare provider if you have any of these symptoms and they are severe.

Get emergency medical help if you have:

  • trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue or throat, extreme drowsiness, or you are feeling faint.

These are not all the possible side effects of EXALGO. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov

Last reviewed on RxList: 7/23/2012
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

Medication Guide

EXALGO®
(eks-al-goh)
(hydromorphone hydrochloride) Extended-Release Tablets

EXALGO is:

  • A strong prescription pain medicine that contains an opioid (narcotic) that is used to treat moderate to severe around-the-clock pain, in people who are already regularly using opioid pain medicine.

Important information about EXALGO:

  • Get emergency help right away if you take too much EXALGO (overdose). EXALGO overdose can cause life threatening breathing problems that can lead to death.
  • Never give anyone else your EXALGO. They could die from taking it. Store EXALGO away from children and in a safe place to prevent stealing or abuse. Selling or giving away EXALGO is against the law.

Do not take EXALGO if you have:

  • severe asthma, trouble breathing, or other lung problems.
  • a bowel blockage or have narrowing of the stomach or intestines.

Before taking EXALGO, tell your healthcare provider if you have a history of:

  • head injury, seizures
  • liver, kidney, thyroid problems
  • allergy to hydromorphone or sulfites
  • problems urinating
  • pancreas or gallbladder problems
  • abuse of street or prescription drugs, alcohol addiction, or mental health problems.

Tell your healthcare provider if you are:

  • pregnant or planning to become pregnant. EXALGO may harm your unborn baby.
  • breastfeeding. EXALGO passes into breast milk and may harm your baby.
  • taking prescription or over-the-counter medicines, vitamins, or herbal supplements.

When taking EXALGO:

  • Do not change your dose. Take EXALGO exactly as prescribed by your healthcare provider.
  • Take your prescribed dose at the same time every day. Do not take more than your prescribed dose in 24 hours. If you miss a dose, do not take EXALGO. Take your next dose at your usual time the next day.
  • Swallow EXALGO whole. Do not cut, break, chew, crush, dissolve, or inject EXALGO.
  • Call your healthcare provider if the dose you are taking does not control your pain.
  • Do not stop taking EXALGO without talking to your healthcare provider.
  • EXALGO is contained in a hard tablet shell that you may see in your bowel movement; this is normal.
  • After you stop taking EXALGO, flush any unused tablets down the toilet.

While taking EXALGO Do Not:

  • Drive or operate heavy machinery, until you know how EXALGO affects you. EXALGO can make you sleepy, dizzy, or lightheaded.
  • Drink alcohol or use prescription or over-the-counter medicines that contain alcohol.

The possible side effects of EXALGO are:

  • constipation, nausea, sleepiness, vomiting, tiredness, headache, dizziness. Call your healthcare provider if you have any of these symptoms and they are severe.

Get emergency medical help if you have:

  • trouble breathing, shortness of breath, fast heartbeat, chest pain, swelling of your face, tongue or throat, extreme drowsiness, or you are feeling faint.

These are not all the possible side effects of EXALGO. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. For more information go to dailymed.nlm.nih.gov

Last reviewed on RxList: 7/23/2012
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Exalgo Consumer

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.

HYDROMORPHONE EXTENDED RELEASE - ORAL

(hye-droe-MOR-fone)

COMMON BRAND NAME(S): Exalgo

WARNING: See also How to Use section.

Hydromorphone has a high risk for abuse and severe, possibly fatal, breathing problems. The risk for harm is higher if you take the wrong dose/strength, or if you take it along with other drugs that might also affect breathing. Be sure you know how to take hydromorphone and what other drugs you should avoid taking with it. Get immediate medical help if you notice unusual slow/shallow breathing.

Keep this medicine in a safe place to prevent theft, misuse, or abuse. If a child accidentally swallows this drug, get emergency medical help right away.

Hydromorphone extended-release should be used only if you have been regularly taking moderate to large amounts of narcotic pain medication. This medication may cause overdose (even death) if taken by a person who has not been regularly taking narcotic medication. This medication should be used only for ongoing pain that requires strong narcotic pain medication at all times for an extended period. It should not be used for quick relief (for use as needed) of sudden, short-term or "breakthrough" pain.

This product is designed to slowly release hydromorphone. Do not break, crush, or chew this medication. Taking broken, crushed, or chewed forms of extended-release hydromorphone could cause overdose.

USES: This medication contains hydromorphone in a long-acting form. It is used to help relieve moderate to severe ongoing pain (such as due to cancer). Hydromorphone belongs to a class of drugs known as narcotic (opiate) analgesics. It works in the brain to change how your body feels and responds to pain.

HOW TO USE: See also Warning section.

Read the Medication Guide and, if available, the Patient Information Leaflet provided by your pharmacist before you start taking this product and each time you get a refill. If you have any questions regarding the information, consult your doctor or pharmacist.

Take this medication by mouth as directed by your doctor, usually once daily at the same time each day, not as needed for sudden (breakthrough) pain. You may take this drug with or without food. If you have nausea, it may help to take this drug with food. Ask your doctor or pharmacist about other ways to decrease nausea (such as lying down for 1 to 2 hours with as little head movement as possible).

Swallow the tablet whole. Do not crush, break, chew, or dissolve the tablet. Doing so can release all of the drug at once, increasing the risk of side effects.

Hydromorphone comes in a rapid-acting form and a slow-release form. Check with your pharmacist to make sure you are taking the correct form.

The dosage is based on your medical condition and response to treatment. Do not increase your dose, take the medication more frequently, or take it for a longer time than prescribed. Properly stop the medication when so directed. If you do not take this medication for 3 days in a row, call your doctor before restarting the medication. Your restarting dose may need to be lower.

Before you start taking this medication, ask your doctor or pharmacist if you should stop or change the dose of your other narcotic medication(s). For added pain relief, your doctor may direct you to also take quick-acting narcotic or non-narcotic pain medications (such as acetaminophen, ibuprofen). Ask your doctor or pharmacist if you have any questions about using hydromorphone safely with other drugs.

This medication may cause withdrawal reactions, especially if it has been used regularly for a long time or in high doses. In such cases, withdrawal symptoms (such as restlessness, watery eyes, runny nose, nausea, sweating, muscle aches) may occur if you suddenly stop using this medication. To prevent withdrawal reactions, your doctor may reduce your dose gradually. Consult your doctor or pharmacist for more details, and report any withdrawal reactions immediately.

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.

Along with its benefits, this medication may rarely cause abnormal drug-seeking behavior (addiction). This risk may be increased if you have abused alcohol or drugs in the past. Take this medication exactly as prescribed to lessen the risk of addiction.

Tell your doctor if your pain persists or worsens.

Disclaimer

Exalgo Consumer (continued)

SIDE EFFECTS: Nausea, vomiting, constipation, lightheadedness, dizziness, or drowsiness may occur. Some of these side effects may decrease after you have been using this medication for a while. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To prevent constipation, eat a diet adequate in fiber, drink plenty of water, and exercise. Consult your pharmacist for help in selecting a laxative (such as a stimulant type with stool softener).

To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

You may notice an empty tablet shell in your stool. This is harmless because your body has already absorbed the medicine.

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 immediately if any of these unlikely but serious side effects occur: mental/mood changes (such as agitation, hallucinations, confusion), severe stomach/abdominal pain, difficulty urinating.

Seek immediate medical attention if any of these rare but serious side effects occur: fainting, slow/shallow breathing, unusual drowsiness/difficulty waking up, seizures.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention 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.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Exalgo (hydromorphone hydrochloride extended release tablets) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking hydromorphone, tell your doctor or pharmacist if you are allergic to hydromorphone; or to other narcotic pain medications (such as morphine); or if you have any other allergies. This product may contain inactive ingredients (such as sulfites), 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: brain disorders (such as head injury, tumor, seizures), breathing problems (such as asthma, sleep apnea, chronic obstructive pulmonary disease-COPD), kidney disease, liver disease, mental/mood disorders (such as confusion, depression), personal or family history of regular use/abuse of drugs/alcohol, stomach/intestinal problems (such as blockage, stomach or bypass surgery, constipation, diarrhea due to infection, paralytic ileus), difficulty swallowing, difficulty urinating (such as due to enlarged prostate).

This drug may make you dizzy or drowsy. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Alcohol may worsen this effect. Avoid alcoholic beverages.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Older adults may be more sensitive to the effects of this drug, especially dizziness, drowsiness, urinary problems.

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, take the smallest effective dose for the shortest possible time. Tell the doctor right away if you notice any symptoms in your newborn baby such as slow/shallow breathing, irritability, abnormal/persistent crying, vomiting, or diarrhea.

This drug passes into breast milk and may have undesirable effects on a nursing infant. Tell the doctor immediately if your baby develops unusual sleepiness, difficulty feeding, or trouble breathing. Consult your doctor before breast-feeding.

Disclaimer

Exalgo Consumer (continued)

DRUG INTERACTIONS: See also Warning section.

The effects of some drugs can change if you take other drugs or herbal products at the same time. This can increase your risk for serious side effects or may cause your medications not to work correctly. These drug interactions are possible, but do not always occur. Your doctor or pharmacist can often prevent or manage interactions by changing how you use your medications or by close monitoring.

To help your doctor and pharmacist give you the best care, be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products) before starting treatment with this product. While using this product, do not start, stop, or change the dosage of any other medicines you are using without your doctor's approval.

Some products that may interact with this drug include: certain medications for pain (narcotic agonists/antagonists such as butorphanol, nalbuphine, pentazocine), narcotic antagonists (such as naltrexone).

The risk of serious side effects (such as slow/shallow breathing, severe drowsiness/dizziness) may be increased if this medication is taken with other products that may also affect breathing or cause drowsiness. Therefore, tell your doctor or pharmacist if you are taking other products such as alcohol, allergy or cough-and-cold products, anti-seizure drugs (such as phenobarbital), medicine for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants, other narcotic pain relievers (such as codeine), and psychiatric medicines (such as risperidone, amitriptyline, trazodone). Your medications or doses of your medications may need to be changed.

This medication may interfere with certain laboratory tests, possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible drug interactions. Keep a list of all the products you use. Share this list with your doctor and pharmacist to lessen your risk for serious medication problems.

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: slow breathing, slow heartbeat, loss of consciousness.

NOTES: Do not share this medication with others. 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.

MISSED DOSE: If you miss a dose, skip the missed dose and resume your usual dosing schedule. Do not take 2 doses in 24 hours. Do not double the dose to catch up.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. 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 September 2011. Copyright(c) 2011 First Databank, Inc.

Exalgo Patient Information Including Side Effects

Brand Names: Dilaudid, Dilaudid-5, Exalgo

Generic Name: hydromorphone (oral) (Pronunciation: HYE droe MOR fone)

What is hydromorphone (Exalgo)?

Hydromorphone is in a group of drugs called narcotic pain relievers, also called opioids. It is similar to morphine.

Hydromorphone is used to treat moderate to severe pain. The extended-release form of this medication is for around-the-clock treatment of pain.

Hydromorphone may also be used for other purposes not listed in this medication guide.

Dilaudid 2 mg ABB

round, orange, imprinted with 2, a

Dilaudid 2 mg

round, orange, imprinted with K, 2

Dilaudid 4 mg

round, yellow, imprinted with 4, a

Dilaudid 8 mg

triangular, white, imprinted with 8, double Abbott Logo (aa)

Hydromorphone 2 mg-ETH

round, blue, imprinted with 2, E

Hydromorphone 2 mg-MAL

round, white, imprinted with M, 2

Hydromorphone 2 mg-ROX

round, white, imprinted with 54 743, 2

Hydromorphone 4 mg-ETH

round, beige, imprinted with 4, E

Hydromorphone 4 mg-MAL

round, white, imprinted with M, 4

Hydromorphone 4 mg-ROX

round, white, imprinted with 4, 54 609

Hydromorphone 8 mg-ETH

round, white, imprinted with E, 8

Hydromorphone 8 mg-ROX

round, white, imprinted with 54 403

What are the possible side effects of hydromorphone (Exalgo)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • shallow breathing, slow heartbeat;
  • seizure (convulsions);
  • cold, clammy skin;
  • confusion;
  • severe weakness or dizziness; or
  • feeling light-headed, fainting.

Less serious side effects are more likely to occur, such as:

  • nausea, vomiting, constipation, loss of appetite;
  • warmth, tingling, or redness under your skin;
  • dizziness, headache;
  • dry mouth;
  • sweating; or
  • itching.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

Read the Exalgo (hydromorphone hydrochloride extended release tablets) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about hydromorphone (Exalgo)?

Hydromorphone may be habit-forming and should be used only by the person it was prescribed for. Never share hydromorphone with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it.

Never take hydromorphone in larger amounts, or for longer than recommended by your doctor. Follow the directions on your prescription label. Tell your doctor if the medicine seems to stop working as well in relieving your pain.

Hydromorphone may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Do not stop using hydromorphone suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to avoid withdrawal symptoms when you stop using hydromorphone.

Side Effects Centers

Exalgo Patient Information including How Should I Take

What should I discuss with my healthcare provider before using hydromorphone (Exalgo)?

Do not use this medication if you have ever had an allergic reaction to a narcotic medicine (examples include codeine, methadone, morphine, Oxycontin, Darvocet, Percocet, Vicodin, Lortab, and many others). You should also not take hydromorphone if you are having an asthma attack or if you have a bowel obstruction called paralytic ileus.

Hydromorphone may be habit-forming and should be used only by the person it was prescribed for. Never share hydromorphone with another person, especially someone with a history of drug abuse or addiction. Keep the medication in a place where others cannot get to it.

If you have any of these other conditions, you may need a hydromorphone dose adjustment or special tests:

  • asthma, COPD, sleep apnea, or other breathing disorders;
  • liver or kidney disease;
  • underactive thyroid;
  • curvature of the spine;
  • a history of head injury or brain tumor;
  • epilepsy or other seizure disorder;
  • low blood pressure;
  • gallbladder disease;
  • Addison's disease or other adrenal gland disorders;
  • enlarged prostate, urination problems;
  • mental illness; or
  • a history of drug or alcohol addiction.

FDA pregnancy category C. It is not known whether hydromorphone will harm an unborn baby. Hydromorphone may cause addiction or withdrawal symptoms in a newborn if the mother takes the medication during pregnancy. Tell your doctor if you are pregnant or plan to become pregnant while using hydromorphone.

Hydromorphone can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

You should not use an extended-release form of hydromorphone (such as Palladone) unless you are already being treated with a similar opioid pain medicine and your body is tolerant to it. Talk with your doctor if you are not sure you are opioid-tolerant.

Older adults may be more sensitive to the effects of this medicine.

How should I use hydromorphone (Exalgo)?

Take exactly as prescribed. Never take hydromorphone in larger amounts, or for longer than recommended by your doctor. Follow the directions on your prescription label. Tell your doctor if the medicine seems to stop working as well in relieving your pain.

Take the pill form of this medicine with a full glass of water.

Do not crush, chew, or break an extended-release tablet. Swallow it whole. Breaking the pill may cause too much of the drug to be released at one time.

Measure liquid medicine with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one. Avoid getting hydromorphone liquid on your skin. It can be absorbed through your skin, and you may get too large a dose.

Do not stop using hydromorphone suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to avoid withdrawal symptoms when you stop using hydromorphone.

Store this medication at room temperature, away from heat, moisture, and light.

Keep track of the amount of medicine used from each new bottle. Hydromorphone is a drug of abuse and you should be aware if anyone is using your medicine improperly or without a prescription.

After you have stopped using this medication, flush any unused pills down the toilet.

Throw away any unused liquid hydromorphone that is older than 90 days.

Side Effects Centers

Exalgo Patient Information including If I Miss a Dose

What happens if I miss a dose (Exalgo)?

Since hydromorphone is taken as needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Extended-release hydromorphone is not for use on an as-needed basis for pain.

What happens if I overdose (Exalgo)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of hydromorphone can be fatal.

Overdose symptoms may include extreme drowsiness, pinpoint pupils, confusion, cold and clammy skin, weak pulse, shallow breathing, fainting, or breathing that stops.

What should I avoid while using hydromorphone (Exalgo)?

Hydromorphone may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

What other drugs will affect hydromorphone (Exalgo)?

Do not take hydromorphone with other narcotic pain medications, sedatives, tranquilizers, muscle relaxers, or other medicines that can make you sleepy or slow your breathing. Dangerous side effects may result.

Before taking hydromorphone, tell your doctor if you are using pentazocine (Talwin), nalbuphine (Nubain), butorphanol (Stadol), or buprenorphine (Buprenex, Subutex). If you are using any of these drugs, you may not be able to use hydromorphone, or you may need dosage adjustments or special tests during treatment.

This list is not complete and other drugs may interact with hydromorphone. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about hydromorphone.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 6.02. Revision date: 12/15/2010.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

Healthwise

Side Effects Centers

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