Hydromorphone

Hydromorphone is a prescription medication used to relieve pain. Hydromorphone belongs to a group of drugs called narcotic analgesics. These work by changing the way that the brain and nervous system respond to pain.

This medication comes in oral solution and tablet forms and is taken up to 4 times a day.

Do not chew, divide, or break hydromorphone extended release tablets. Swallow these tablets whole.

This medication is also available in an injectable form to be given directly into a vein (IV), a muscle (IM), or under the skin (subcutaneous).

Common side effects of hydromorphone include nausea, vomiting, constipation, drowsiness, lightheadedness, anxiety, mood changes, rash, and itching.

Hydromorphone can also cause drowsiness and dizziness. Do not drive or operate heavy machinery until you know how hydromorphone affects you.

In the U.S.

• Dilaudid
• Dilaudid-5
• Exalgo
• Palladone

Available Dosage Forms:

• Liquid
• Tablet, Extended Release
• Capsule, Extended Release
• Tablet
• Solution

Therapeutic Class: Analgesic

Chemical Class: Opioid

Hydromorphone oral liquid and tablets are used to relieve pain. The hydromorphone extended-release capsules and extended-release tablets are used to relieve moderate to severe pain in opioid-tolerant patients who require around-the-clock pain relief for a long period of time.

Hydromorphone extended-release capsules and extended-release tablets should not be used if you need pain medicine for just a short time, such as when recovering from surgery. Do not use hydromorphone to relieve mild pain. hydromorphone should not be used to treat pain that you only have once in a while or "as needed".

Hydromorphone belongs to the group of medicines called narcotic analgesics (pain medicines). It acts on the central nervous system (CNS) to relieve pain.

When a narcotic medicine is used for a long time, it may become habit-forming, causing mental or physical dependence. However, people who have continuing pain should not let the fear of dependence keep them from using narcotics to relieve their pain. Mental dependence (addiction) is not likely to occur when narcotics are used for this purpose. Physical dependence may lead to withdrawal side effects if treatment is stopped suddenly. However, severe withdrawal side effects can usually be prevented by gradually reducing the dose over a period of time before treatment is stopped completely.

hydromorphone is available only with your doctor's prescription.

It is very important that your doctor check your progress while you are using hydromorphone. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it.

hydromorphone will add to the effects of alcohol and other CNS depressants (medicines that can make you drowsy or less alert). CNS depressants are medicines that slow down the nervous system, which may cause drowsiness or make you less alert. Some examples of CNS depressants are antihistamines or medicine for hay fever, allergies, or colds, sedatives, tranquilizers, or sleeping medicine, other prescription pain medicine or narcotics, medicine for seizures or barbiturates, muscle relaxants, or anesthetics (numbing medicines), including some dental anesthetics. This effect may last for a few days after you stop using hydromorphone. Check with your doctor before taking any of the other medicines listed above while you are using hydromorphone.

hydromorphone may be habit-forming. If you feel that the medicine is not working as well, do not use more than your prescribed dose. Call your doctor for instructions.

Dizziness, lightheadedness, or fainting may occur when you get up suddenly from a lying or sitting position. Getting up slowly may help lessen this problem. Also, lying down for a while may relieve dizziness or lightheadedness.

Using narcotics for a long time can cause severe constipation. To prevent this, your doctor may direct you to take laxatives, drink a lot of fluids, or increase the amount of fiber in your diet. Be sure to follow the directions carefully, because continuing constipation can lead to more serious problems.

hydromorphone may make you dizzy, drowsy, or lightheaded. Make sure you know how you react to hydromorphone before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert.

hydromorphone may cause serious allergic reactions, including anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth while you are using hydromorphone.

If you have been using hydromorphone regularly for several weeks or more, do not change your dose or suddenly stop using it without first checking with your doctor. You may be directed to gradually reduce the amount you are using before stopping treatment completely, or to take another narcotic for a while, to lessen the chance of withdrawal side effects (eg, abdominal or stomach cramps, anxiety, fever, nausea, runny nose, sweating, tremors, or trouble with sleeping).

Do not take too much of hydromorphone. This can be life-threatening. Symptoms of an overdose include: extreme dizziness or weakness, slow heartbeat or breathing, seizures, trouble breathing, and cold, clammy skin. Call your doctor right away if you notice these symptoms.

Using hydromorphone while you are pregnant may cause neonatal withdrawal syndrome in your newborn babies. Tell your doctor right away if your baby has an abnormal sleep pattern, diarrhea, a high-pitched cry, irritability, shakiness or tremors, weight loss, vomiting, or fails to gain weight.

Check with your doctor right away if you have anxiety, restlessness, a fast heartbeat, fever, sweating, muscle spasms, twitching, nausea, vomiting, diarrhea, or see or hear things that are not there. These may be symptoms of a serious condition called serotonin syndrome. Your risk may be higher if you also take certain other medicines that affect serotonin levels in your body.

Using too much of hydromorphone may cause infertility (unable to have children). Talk with your doctor before using hydromorphone if you plan to have children.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Hydromorphone Hydrochloride Tablets USP, 2 mg, 4 mg, and 8 mg are supplied in tablet form for oral administration.

Hydromorphone hydrochloride, a hydrogenated ketone of morphine, is an opioid analgesic.

The chemical name of Hydromorphone hydrochloride tablets USP is 4,5α-epoxy-3-hydroxy-17-methylmorphinan-6-one hydrochloride. The structural formula of Hydromorphone hydrochloride is:

Each Hydromorphone Hydrochloride Tablet USP, 2 mg contains: 
    Hydromorphone Hydrochloride USP . . . . . . . . . . . . 2 mg

Each Hydromorphone Hydrochloride Tablet USP, 4 mg contains: 
    Hydromorphone Hydrochloride USP . . . . . . . . . . . . 4 mg

Each Hydromorphone Hydrochloride Tablet USP, 8 mg contains: 
    Hydromorphone Hydrochloride USP . . . . . . . . . . . . 8 mg

In addition, each tablet contains the following inactive ingredients: lactose monohydrate, magnesium stearate, microcrystalline cellulose and stearic acid.

The precise mode of analgesic action of opioid analgesics is unknown. However, specific CNS opiate receptors have been identified. Opioids are believed to express their pharmacological effects by combining with these receptors.

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

Hydromorphone depresses the respiratory reflex by a direct effect on brain stem respiratory centers. The mechanism of respiratory depression also involves a reduction in the responsiveness of the brain stem respiratory centers to increases in carbon dioxide tension.

Hydromorphone causes miosis. Pinpoint pupils are a common sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origin may produce similar findings). Marked mydriasis rather than miosis may be seen with hypoxia in the setting of Hydromorphone hydrochloride tablets overdose.

Hydromorphone hydrochloride tablets USP are indicated for the management of pain in patients where an opioid analgesic is appropriate.

Special Risk Patients – Hydromorphone hydrochloride tablets should be given with caution and the initial dose should be reduced in the elderly or debilitated and those with severe impairment of hepatic, pulmonary or renal functions; myxedema or hypothyroidism; adrenocortical insufficiency (e.g., Addison's Disease); CNS depression or coma; toxic psychoses; prostatic hypertrophy or urethral stricture; gall bladder disease; acute alcoholism; delirium tremens; kyphoscoliosis or following gastrointestinal surgery.

The administration of opioid analgesics including Hydromorphone hydrochloride tablets may obscure the diagnoses or clinical course in patients with acute abdominal conditions and may aggravate preexisting convulsions in patients with convulsive disorders.

Reports of mild to severe seizures and myoclonus have been reported in severely compromised patients, administered high doses of parenteral Hydromorphone, for cancer and severe pain. Opioid administration at very high doses is associated with seizures and myoclonus in a variety of diseases where pain control is the primary focus.

Use in Drug and Alcohol Dependent Patients – Hydromorphone hydrochloride tablets should be used with caution in patients with alcoholism and other drug dependencies due to the increased frequency of opioid tolerance, dependence, and the risk of addiction observed in these patient populations. Abuse of Hydromorphone hydrochloride tablets in combination with other CNS depressant drugs can result in serious risk to the patient.

Hydromorphone is an opioid with no approved use in the management of addictive disorders.

Use in Ambulatory Patients – Hydromorphone hydrochloride tablets may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating machinery). Patients should be cautioned accordingly. Hydromorphone hydrochloride may produce orthostatic hypotension in ambulatory patients.

Use in Biliary Tract Disease – Opioid analgesics including Hydromorphone hydrochloride tablets should also be used with caution in patients about to undergo surgery of the biliary tract since it may cause spasm of the sphincter of Oddi.

Analgesics – Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, butorphanol, and buprenorphine) should be administered with caution to a patient who has received or is receiving a course of therapy with a pure opioid agonist analgesic such as Hydromorphone. In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of Hydromorphone and/or may precipitate withdrawal symptoms in these patients.

No carcinogenicity studies have been conducted in animals.

Hydromorphone was not mutagenic in the in vitro Ames reverse mutation assay or the human lymphocyte chromosome aberration assay. Hydromorphone was not clastogenic in the in vivo mouse micronucleus assay.

No effects on fertility, reproductive performance, or reproductive organ morphology were observed in male or female rats given oral doses up to 7 mg/kg/day, which is equivalent to the human dose of 2.5 to 10 mg every 3 to 6 hours for oral liquid, and 3-fold higher than the human dose of 2 to 4 mg every 4 to 6 hours for the tablet on a body surface area basis.

NDC 0406-3249-01

100 TABLETS

Hydromorphone HYDROCHLORIDE
TABLETS USP

CII

8 mg

Rx only

Each tablet contains: Hydromorphone Hydrochloride USP ..... 8 mg

Mallinckrodt™

L00H79

Rev 02/2016

• Dihydromorphinone
• Hydromorphone HCl
• Hydromorphone Hydrochloride
• Palladone

Extended release: Cmax and AUC are increased 2-fold in patients with moderate (CrCl 40 to 60 mL/minute) and 4-fold in patients with severe (CrCl <30 mL/minute) renal impairment.

Immediate release: Cmax and AUC0-48 are increased 2-fold in patients with moderate (CrCl 40 to 60 mL/minute) and 3-fold in patients with severe (CrCl <30 mL/minute) renal impairment.

Parenteral: Note: Vial stopper may contain latex. May be given SubQ or IM; IM route is not recommended (APS 2008). Hydromorphone HP (10 mg/mL) is a more concentrated solution of hydromorphone than hydromorphone 1, 2, or 4 mg/mL, and is for use in opioid-tolerant patients only. Do not confuse hydromorphone HP with standard parenteral formulations of hydromorphone or other opioids, as overdose and death could result.

IV: For IVP, must be given slowly over at least 2 to 3 minutes (rapid IVP has been associated with an increase in side effects, especially respiratory depression and hypotension)

Oral: Hydromorphone is available in an 8 mg immediate-release tablet and an 8 mg extended-release tablet. Extreme caution should be taken to avoid confusing dosage forms.

Hydromorphone ER, Jurnista [Canadian product]: Tablets should be swallowed whole; do not crush, break, chew, dissolve, snort, or inject. Administer with or without food.

Hydromorph Contin [Canadian product]: For oral use only. Capsule should be swallowed whole; do not crush or chew. Contents may be sprinkled on a tablespoon of applesauce (stored at room temperature or under refrigeration) or custard (stored at room temperature) and swallowed without chewing as soon as possible (discard if not consumed within 30 minutes); patient should then rinse mouth with water to ensure entire contents are swallowed.

Oral solution: Ensure accuracy when prescribing, dispensing, and administering. Dosing errors due to confusion between mg and mL can result in accidental overdose and death. A calibrated oral syringe/dosing cup that can measure and deliver the prescribed dose accurately should be used; do not use a household teaspoon or tablespoon to measure dose.

Some quinolones may produce a false-positive urine screening result for opioids using commercially-available immunoassay kits. This has been demonstrated most consistently for levofloxacin and ofloxacin, but other quinolones have shown cross-reactivity in certain assay kits. Confirmation of positive opioid screens by more specific methods should be considered.

Concerns related to adverse effects:

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Constipation: May cause constipation which may be problematic in patients with unstable angina and patients post-myocardial infarction. Consider preventive measures to reduce the potential for constipation. Use with extreme caution in patients with chronic constipation.

• Hypotension: May cause severe hypotension (including orthostatic hypotension and syncope); use with caution in patients with hypovolemia, cardiovascular disease (including acute myocardial infarction [MI]), or drugs that may exaggerate hypotensive effects (including phenothiazines or general anesthetics). Monitor for symptoms of hypotension following initiation or dose titration. Avoid use in patients with circulatory shock.

• Phenanthrene hypersensitivity: Use with caution in patients with hypersensitivity reactions to other phenanthrene derivative opioid agonists (codeine, hydrocodone, levorphanol, oxycodone, oxymorphone).

• Respiratory depression: [US Boxed Warning]: Serious, life-threatening, or fatal respiratory depression may occur. Monitor closely for respiratory depression, especially during initiation or dose escalation. Swallow ER tablets whole; crushing, chewing, or dissolving can cause rapid release and a potentially fatal dose. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.

Disease-related concerns:

• Abdominal conditions: May obscure diagnosis or clinical course of patients with acute abdominal conditions.

• Adrenocortical insufficiency: Use with caution in patients with adrenal insufficiency, including Addison disease. Long-term opioid use may cause secondary hypogonadism, which may lead to sexual dysfunction, infertility, mood disorders, and osteoporosis (Brennan, 2013).

• Biliary tract impairment: Use with caution in patients with biliary tract dysfunction, including acute pancreatitis; opioids may cause constriction of sphincter of Oddi.

• CNS depression/coma: Avoid use in patients with impaired consciousness or coma, as these patients are susceptible to intracranial effects of CO2 retention.

• Delirium tremens: Use with caution in patients with delirium tremens.

• GI narrowing: Hydromorphone ER tablets are nondeformable; do not administer to patients with preexisting severe GI narrowing (eg, esophageal motility, small bowel inflammatory disease, short gut syndrome, history of peritonitis, cystic fibrosis, chronic intestinal pseudo-obstruction, Meckel’s diverticulum); obstruction may occur.

• Head trauma: Use with extreme caution in patients with head injury, intracranial lesions, or elevated intracranial pressure (ICP); exaggerated elevation of ICP may occur.

• Hepatic impairment: Use with caution in patients with hepatic impairment; dosage reduction recommended in moderate to severe impairment. ER tablets are not recommended in severe impairment.

• Mental health conditions: Use opioids with caution for chronic pain in patients with mental health conditions (eg, depression, anxiety disorders, post-traumatic stress disorder) due to increased risk for opioid use disorder and overdose; more frequent monitoring is recommended (Dowell [CDC 2016]).

• Obesity: Use with caution in patients who are morbidly obese.

• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture.

• Psychosis: Use with caution in patients with toxic psychosis.

• Renal impairment: Use with caution in patients with renal impairment; dosage reduction recommended. ER tablets are not recommended in severe impairment.

• Respiratory disease: Use with caution and monitor for respiratory depression in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression, particularly when initiating and titrating therapy; critical respiratory depression may occur, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

• Seizures: Use with caution in patients with a history of seizure disorders; may cause or exacerbate preexisting seizures.

• Sleep-disordered breathing: Use opioids with caution for chronic pain and titrate dosage cautiously in patients with risk factors for sleep-disordered breathing, including HF and obesity. Avoid opioids in patients with moderate to severe sleep-disordered breathing (Dowell [CDC 2016]).

• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Concurrent drug therapy issues:

• Benzodiazepines or other CNS depressants: [US Boxed Warning]: Concomitant use of opioids with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of hydromorphone and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Limit dosage and durations to the minimum required and follow patients for signs and symptoms of respiratory depression and sedation.

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Cachectic or debilitated patients: Use with caution in cachectic or debilitated patients; there is a greater potential for critical respiratory depression, even at therapeutic dosages. Consider the use of alternative nonopioid analgesics in these patients.

• Elderly: Use with caution in the elderly; may be more sensitive to adverse effects. Decrease initial dose. Use opioids for chronic pain with caution in this age group; monitor closely due to an increased potential for risks, including certain risks such as falls/fracture, cognitive impairment, and constipation. Clearance may also be reduced in older adults (with or without renal impairment) resulting in a narrow therapeutic window and increasing the risk for respiratory depression or overdose (Dowell [CDC 2016]). Consider the use of alternative nonopioid analgesics in these patients.

• Neonates: Neonatal withdrawal syndrome: [US Boxed Warning]: Prolonged use of opioids during pregnancy can cause neonatal withdrawal syndrome, which may be life-threatening if not recognized and treated according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available. Signs and symptoms include irritability, hyperactivity and abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. Onset, duration, and severity depend on the drug used, duration of use, maternal dose, and rate of drug elimination by the newborn.

Dosage form specific issues:

• Extended-release tablets: Therapy should only be prescribed by health care professionals familiar with the use of potent opioids for chronic pain. Tablets may be visible on abdominal x-rays, especially when digital enhancing techniques are used. The tablet shell may appear in the excreted stool.

• Oral solution: [US Boxed Warning]: Ensure accuracy when prescribing, dispensing, and administering hydromorphone oral solution. Dosing errors due to confusion between mg and mL can result in accidental overdose and death.

• Injection: [US Boxed Warning]: High-potency hydromorphone (10 mg/mL) is a more concentrated solution of hydromorphone than hydromorphone 1, 2, or 4 mg/mL, and is for use in opioid-tolerant patients only. Do not confuse high-potency hydromorphone with standard parenteral formulations of hydromorphone or other opioids, as overdose and death could result.

• Lactose: Some formulations may contain lactose.

• Latex: Vial stoppers of single-dose injectable vials may contain latex.

• Sodium metabisulfite: Some dosage forms may contain trace amounts of sodium metabisulfite, which may cause allergic reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible individuals.

Other warnings/precautions:

• Abuse/misuse/diversion: [US Boxed Warning]: Hydromorphone exposes patients and other users to the risks of addiction, abuse, and misuse, potentially leading to overdose and death. Assess each patient’s risk prior to prescribing; monitor all patients regularly for development of these behaviors or conditions. Use with caution in patients with a history of drug abuse or acute alcoholism; potential for drug dependency exists. Other factors associated with increased risk for misuse include younger age, concomitant depression (major), and psychotropic medication use. Consider offering naloxone prescriptions in patients with factors associated with an increased risk for overdose, such as history of overdose or substance use disorder, higher opioid dosages (≥50 morphine milligram equivalents/day orally), and concomitant benzodiazepine use (Dowell [CDC 2016]).

• Accidental exposure: [US Boxed Warning]: Accidental ingestion of even one dose, especially in children, can result in a fatal overdose of hydromorphone.

• Appropriate use: Chronic pain (outside of end-of-life or palliative care, active cancer treatment, sickle cell disease, or medication-assisted treatment for opioid use disorder) in outpatient setting in adults: Opioids should not be used as first-line therapy for chronic pain management (pain >3-month duration or beyond time of normal tissue healing) due to limited short-term benefits, undetermined long-term benefits, and association with serious risks (eg, overdose, MI, auto accidents, risk of developing opioid use disorder). Preferred management includes nonpharmacologic therapy and nonopioid therapy (eg. NSAIDs, acetaminophen, certain anticonvulsants and antidepressants). If opioid therapy is initiated, it should be combined with nonpharmacologic and nonopioid therapy, as appropriate. Prior to initiation, known risks of opioid therapy should be discussed and realistic treatment goals for pain/function should be established, including consideration for discontinuation if benefits do not outweigh risks. Therapy should be continued only if clinically meaningful improvement in pain/function outweighs risks. Therapy should be initiated at the lowest effective dosage using immediate-release opioids (instead of extended-release/long-acting opioids). Risk associated with use increases with higher opioid dosages. Risks and benefits should be re-evaluated when increasing dosage to ≥50 morphine milligram equivalents (MME)/day orally; dosages ≥90 MME/day orally should be avoided unless carefully justified (Dowell [CDC 2016]).

• IM administration: Variable absorption and a lag time to peak effect may result from IM use.

• IV administration: Administer IV very slowly; rapid IV injection of opioid analgesics increases the possibility of side effects such as hypotension and respiratory depression.

• Optimal regimen: An opioid-containing analgesic regimen should be tailored to each patient's needs and based upon the type of pain being treated (acute versus chronic), the route of administration, degree of tolerance for opioids (naive versus chronic user), age, weight, and medical condition. The optimal analgesic dose varies widely among patients; doses should be titrated to pain relief/prevention.

• Surgery: Use immediate-release formulations with caution in the perioperative setting; severe pain may antagonize the respiratory depressant effects of hydromorphone. Opioids decrease bowel motility; monitor for decreased bowel motility in postop patients receiving opioids. Use with caution in the perioperative setting; individualize treatment when transitioning from parenteral to oral analgesics.

• Withdrawal: Concurrent use of mixed agonist/antagonist analgesics (eg, pentazocine, nalbuphine, butorphanol) or partial agonist (eg, buprenorphine) analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with mu opioid agonists. Taper dose gradually when discontinuing.