Hydromorphone Hydrochloride 8 MG Oral Tablet
DRUG INTERACTIONS
7 Table 1 includes clinically significant drug interactions with Hydromorphone Hydrochloride.
Table 1: Clinically Significant Drug Interactions with Hydromorphone Hydrochloride Benzodiazepines and other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death.
Intervention: Reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
Limit dosages and durations to the minimum required.
Follow patients closely for signs of respiratory depression and sedation [see Warnings and Precautions ( 5.5 )] .
Examples: Benzodiazepines and other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol.
Serotonergic Drugs Clinical Impact: The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Intervention: If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation and dose adjustment.
Discontinue Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets if serotonin syndrome is suspected.
Examples: Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), triptans, 5-HT3 receptor antagonists, drugs that affect the serotonin neurotransmitter system (e.g., mirtazapine, trazodone, tramadol), monoamine oxidase (MAO) inhibitors (those intended to treat psychiatric disorders and also others, such as linezolid and intravenous methylene blue).
Monoamine Oxidase Inhibitors (MAOIs) Clinical Impact: MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma) [see Warnings and Precautions ( 5.3 )].
If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
Intervention: The use of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets is not recommended for patients taking MAOIs or within 14 days of stopping treatment.
Examples: Phenelzine, tranylcypromine, linezolid.
Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics Clinical Impact: May reduce the analgesic effect of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets and/or precipitate withdrawal symptoms.
Intervention: Avoid concomitant use.
Examples: Butorphanol, nalbuphine, pentazocine, buprenorphine.
Muscle Relaxants Clinical Impact: Hydromorphone may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.
Intervention: Monitor patients for signs of respiratory depression that may be greater than otherwise expected and decrease the dosage of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets and/or the muscle relaxant as necessary.
Diuretics Clinical Impact: Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone.
Intervention: Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.
Anticholinergic Drugs Clinical Impact: The concomitant use of anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.
Intervention: Monitor patients for signs of urinary retention or reduced gastric motility when Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets is used concomitantly with anticholinergic drugs.
• Serotonergic Drugs : Concomitant use may result in serotonin syndrome.
Discontinue Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets if serotonin syndrome is suspected.
( 7 ) • Monoamine Oxidase Inhibitors (MAOIs): Can potentiate the effects of hydromorphone.
Avoid concomitant use in patients receiving MAOIs or within 14 days of stopping treatment with an MAOI.
( 7 ) • Mixed Agonist/Antagonist and Partial Agonist Opioid Analgesics : Avoid use with Hydromorphone Hydrochloride because they may reduce analgesic effect of Hydromorphone Hydrochloride or precipitate withdrawal symptoms.
( 7 )
OVERDOSAGE
10 Clinical Presentation Acute overdose with Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets can be manifested by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and, in some cases, pulmonary edema, bradycardia, hypotension, partial or complete airway obstruction, atypical snoring, and death.
Marked mydriasis rather than miosis may be seen with hypoxia in overdose situations [see Clinical Pharmacology ( 12.2 )].
Treatment of Overdose In case of overdose, priorities are the reestablishment of a patent and protected airway and institution of assisted or controlled ventilation, if needed.
Employ other supportive measures (including oxygen and 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, naloxone or nalmefene, are specific antidotes to respiratory depression resulting from opioid overdose.
For clinically significant respiratory or circulatory depression secondary to hydromorphone overdose, administer an opioid antagonist.
Opioid antagonists should not be administered in the absence of clinically significant respiratory or circulatory depression secondary to hydromorphone overdose.
Because the duration of opioid reversal is expected to be less than the duration of action of hydromorphone in Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets, carefully monitor the patient until spontaneous respiration is reliably reestablished.
If the response to an opioid antagonist is suboptimal or only brief in nature, administer additional antagonist as directed by the product’s prescribing information.
In an individual physically dependent on opioids, administration of the recommended usual dosage of the antagonist will precipitate an acute withdrawal syndrome.
The severity of the withdrawal symptoms experienced 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 initiated with care and by titration with smaller than usual doses of the antagonist.
DESCRIPTION
11 Hydromorphone hydrochloride, a hydrogenated ketone of morphine, is an opioid analgesic.
Hydromorphone hydrochloride USP is a white to off-white powder.
It is soluble in water and sparingly soluble in alcohol.
The chemical name of hydromorphone hydrochloride is 4,5-Epoxy-3-hydroxy-17-methylmorphinan-6-one hydrochloride.
The structural formula is: C 17 H 19 NO 3 ●HCl M.W.
321.80 Each Hydromorphone Hydrochloride Tablet USP for oral administration, contains 4 mg or 8 mg hydromorphone hydrochloride USP.
In addition, the tablets include lactose anhydrous and magnesium stearate.
Hydromorphone Hydrochloride Tablets USP may contain traces of sodium metabisulfite.
Each 5 mL (1 teaspoonful) of Hydromorphone Hydrochloride Oral Solution USP contains 5 mg of hydromorphone hydrochloride USP.
In addition, other ingredients include FD&C Red No.
40, methyl paraben, propylene glycol, propylparaben, purified water, raspberry blend, saccharin sodium and sorbitol solution.
Hydromorphone Hydrochloride Oral Solution USP may contain traces of sodium metabisulfite.
hydromorphone-chem.jpg
CLINICAL STUDIES
14 Analgesic effects of single doses of Hydromorphone Hydrochloride Oral Solution administered to patients with post-surgical pain have been studied in double-blind controlled trials.
In one study, both 5 mg and 10 mg of Hydromorphone Hydrochloride Oral Solution provided significantly more analgesia than placebo.
In another trial, 5 mg and 10 mg of Hydromorphone Hydrochloride Oral Solution were compared to 30 mg and 60 mg of morphine sulfate oral liquid.
The pain relief provided by 5 mg and 10 mg Hydromorphone Hydrochloride Oral Solution was comparable to 30 mg and 60 mg oral morphine sulfate, respectively.
HOW SUPPLIED
16 /STORAGE AND HANDLING Product: 63629-4521
RECENT MAJOR CHANGES
Boxed Warning 12/2016 Indications and Usage ( 1 ) 12/2016 Dosage and Administration ( 2 ) 12/2016 Warnings and Precautions ( 5 ) 12/2016
GERIATRIC USE
8.5 Geriatric Use Elderly patients (aged 65 years or older) may have increased sensitivity to hydromorphone.
In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.
Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration.
Titrate the dosage of Hydromorphone Hydrochloride slowly in geriatric patients and monitor closely for signs of central nervous system and respiratory depression [see Warnings and Precautions ( 5.6 )].
Hydromorphone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function.
Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
DOSAGE FORMS AND STRENGTHS
3 Hydromorphone Hydrochloride Oral Solution USP • 5 mg/5 mL (1 mg/mL) of hydromorphone hydrochloride USP in a clear, red solution.
Hydromorphone Hydrochloride Tablets USP • 4 mg tablets (white to off-white, round, flat-faced tablet with beveled edges; debossed with “4” on one side and “54 196” debossed on the other side) • 8 mg tablets (white to off-white, round, flat-faced tablet with beveled edges: scored on one side and “54 425” debossed on the other side) • Hydromorphone Hydrochloride Oral Solution: 5 mg/5 mL (1 mg/mL) • Hydromorphone Hydrochloride Tablets: 4 mg, 8 mg ( 3 )
MECHANISM OF ACTION
12.1 Mechanism of Action Hydromorphone is a full opioid agonist and is relatively selective for the mu-opioid receptor, although it can bind to other opioid receptors at higher doses.
The principal therapeutic action of hydromorphone is analgesia.
Like all full opioid agonists, there is no ceiling effect for analgesia with morphine.
Clinically, dosage is titrated to provide adequate analgesia and may be limited by adverse reactions, including respiratory and CNS depression.
The precise mechanism of the analgesic action is unknown.
However, specific CNS opioid receptors for endogenous compounds with opioid-like activity have been identified throughout the brain and spinal cord and are thought to play a role in the analgesic effects of this drug.
INDICATIONS AND USAGE
1 Hydromorphone Hydrochloride Oral Solution and Hydromorphone Hydrochloride Tablets are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.
Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see Warnings and Precautions ( 5.2 )], reserve Hydromorphone Hydrochloride Oral Solution and Hydromorphone Hydrochloride Tablets for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: • Have not been tolerated, or are not expected to be tolerated, • Have not provided adequate analgesia, or are not expected to provide adequate analgesia.
Hydromorphone Hydrochloride Tablets and Hydromorphone Hydrochloride Oral Solution contain hydromorphone, an opioid agonist, and are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.
( 1 ) Limitations of Use ( 1 ) Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, reserve Hydromorphone Hydrochloride Tablets or Hydromorphone Hydrochloride Oral Solution for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: • Have not been tolerated, or are not expected to be tolerated, • Have not provided adequate analgesia, or are not expected to provide adequate analgesia.
PEDIATRIC USE
8.4 Pediatric Use The safety and effectiveness of Hydromorphone Hydrochloride in pediatric patients have not been established.
PREGNANCY
8.1 Pregnancy Risk Summary Prolonged use of opioid analgesics during pregnancy may cause neonatal opioid withdrawal syndrome [see Warnings and Precautions ( 5.4 )].
There are no available data with Hydromorphone Hydrochloride in pregnant women to inform a drug-associated risk for major birth defects and miscarriage.
In animal reproduction studies, reduced postnatal survival of pups, and decreased were noted following oral treatment of pregnant rats with hydromorphone during gestation and through lactation at doses 0.8 times the human daily dose of 24 mg/day (HDD), respectively.
In published studies, neural tube defects were noted following subcutaneous injection of hydromorphone to pregnant hamsters at doses 6.4 times the HDD and soft tissue and skeletal abnormalities were noted following subcutaneous continuous infusion of 3 times the HDD to pregnant mice.
No malformations were noted at 4 or 40.5 times the HDD in pregnant rats or rabbits, respectively [see Data].
Based on animal data, advise pregnant women of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.
In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations Fetal/Neonatal Adverse Reactions : Prolonged use of opioid analgesics during pregnancy for medical or nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth.
Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea and failure to gain weight.
The onset, duration, and severity of neonatal opioid withdrawal syndrome vary based on the specific opioid used, duration of use, timing and amount of last maternal use, and rate of elimination of the drug by the newborn.
Observe newborns for symptoms of neonatal opioid withdrawal syndrome and manage accordingly [see Warnings and Precautions ( 5.4 )].
Labor or Delivery : Opioids cross the placenta and may produce respiratory depression and psycho-physiologic effects in neonates.
An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate.
Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate.
Opioid analgesics, including Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions.
However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor.
Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.
Data Animal Data : Pregnant rats were treated with hydromorphone hydrochloride from Gestation Day 6 to 17 via oral gavage doses of 1, 5, or 10 mg/kg/day (0.4, 2, or 4 times the HDD of 24 mg based on body surface area, respectively).
Maternal toxicity was noted in all treatment groups (reduced food consumption and body weights in the two highest dose groups).
There was no evidence of malformations or embryotoxicity reported.
Pregnant rabbits were treated with hydromorphone hydrochloride from Gestation Day 7 to 19 via oral gavage doses of 10, 25, or 50 mg/kg/day (8.1, 20.3, or 40.5 times the HDD of 24 mg based on body surface area, respectively).
Maternal toxicity was noted in the two highest dose groups (reduced food consumption and body weights).
There was no evidence of malformations or embryotoxicity reported.
In a published study, neural tube defects (exencephaly and cranioschisis) were noted following subcutaneous administration of hydromorphone hydrochloride (19 to 258 mg/kg) on Gestation Day 8 to pregnant hamsters (6.4 to 87.2 times the HDD of 24 mg/day based on body surface area).
The findings cannot be clearly attributed to maternal toxicity.
No neural tube defects were noted at 14 mg/kg (4.7 times the human daily dose of 24 mg/day).
In a published study, CF-1 mice were treated subcutaneously with continuous infusion of 7.5, 15, or 30 mg/kg/day hydromorphone hydrochloride (1.5, 3, or 6.1 times the human daily dose of 24 mg based on body surface area) via implanted osmotic pumps during organogenesis (Gestation Days 7 to 10).
Soft tissue malformations (cryptorchidism, cleft palate, malformed ventricles and retina), and skeletal variations (split supraoccipital, checkerboard and split sternebrae, delayed ossification of the paws and ectopic ossification sites) were observed at doses 3 times the human dose of 24 mg/day based on body surface area.
The findings cannot be clearly attributed to maternal toxicity.
Increased pup mortality and decreased pup body weights were noted at 0.8 and 2 times the human daily dose of 24 mg in a study in which pregnant rats were treated with hydromorphone hydrochloride from Gestation Day 7 to Lactation Day 20 via oral gavage doses of 0, 0.5, 2, or 5 mg/kg/day (0.2, 0.8, or 2 times the HDD of 24 mg based on body surface area, respectively).
Maternal toxicity (decreased food consumption and body weight gain) was also noted at the two highest doses tested.
BOXED WARNING
WARNING: RISK OF MEDICATION ERRORS; ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Risk of Medication Errors Ensure accuracy when prescribing, dispensing, and administering Hydromorphone Hydrochloride Oral Solution.
Dosing errors due to confusion between mg and mL can result in accidental overdose and death [see Dosage and Administration ( 2.1 ), Warnings and Precautions ( 5.1 )].
Addiction, Abuse, and Misuse Hydromorphone Hydrochloride Oral Solution and Hydromorphone Hydrochloride Tablets expose patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death.
Assess each patient’s risk prior to prescribing Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets, and monitor all patients regularly for the development of these behaviors and conditions [see Warnings and Precautions ( 5.2 )].
Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of Hydromorphone Hydrochloride Oral Solution and Hydromorphone Hydrochloride Tablets.
Monitor for respiratory depression, especially during initiation of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets or following a dose increase [see Warnings and Precautions ( 5.3 )].
Accidental Ingestion Accidental ingestion of even one dose of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets, especially by children, can result in a fatal overdose of hydromorphone [see Warnings and Precautions ( 5.3 )].
Neonatal Opioid Withdrawal Syndrome Prolonged use of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts.
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 [see Warnings and Precautions ( 5.4 )].
Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death [see Warnings and Precautions ( 5.5 ), Drug Interactions ( 7 )].
• Reserve concomitant prescribing of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.
• Limit dosages and durations to the minimum required.
• Follow patients for signs and symptoms of respiratory depression and sedation.
WARNING: RISK OF MEDICATION ERRORS; ADDICTION, ABUSE, AND MISUSE; LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS See full prescribing information for complete boxed warning.
• Ensure accuracy when prescribing, dispensing, and administering Hydromorphone Hydrochloride Oral Solution.
Dosing errors due to confusion between mg and mL can result in accidental overdose and death.
( 2.1 , 5.1 ) • Hydromorphone Hydrochloride Tablets or Hydromorphone Hydrochloride Oral Solution exposes users to risks of addiction, abuse, and misuse, which can lead to overdose and death.
Assess patient’s risk before prescribing and monitor regularly for these behaviors and conditions.
( 5.2 ) • Serious, life-threatening, or fatal respiratory depression may occur.
Monitor closely, especially upon initiation or following a dose increase.
( 5.3 ) • Accidental ingestion of Hydromorphone Hydrochloride Tablets or Hydromorphone Hydrochloride Oral Solution, especially by children, can result in a fatal overdose of hydromorphone.
( 5.3 ) • Prolonged use of Hydromorphone Hydrochloride Tablets or Hydromorphone Hydrochloride Oral Solution during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated.
If prolonged opioid use is required in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.
( 5.4 ) • Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.
Reserve concomitant prescribing for use in patients for whom alternative treatment options are inadequate; limit dosages and durations to the minimum required; and follow patients for signs and symptoms of respiratory depression and sedation.
( 5.5 , 7 )
WARNING AND CAUTIONS
5 WARNINGS AND PRECAUTIONS • Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients: Monitor closely, particularly during initiation and titration.
( 5.6 ) • Adrenal Insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid.
( 5.7 ) • Severe Hypotension : Monitor during dosage initiation and titration.
Avoid use of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets in patients with circulatory shock.
( 5.8 ) • Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness: Monitor for sedation and respiratory depression.
Avoid use of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets in patients with impaired consciousness or coma.
( 5.9 ) 5.1 Risk of Accidental Overdose and Death due to Medication Errors Dosing errors can result in accidental overdose and death.
Ensure that the dose is communicated clearly and dispensed accurately.
A household teaspoon or tablespoon is not an adequate measuring device.
Given the inexactitude of the household spoon measure and the possibility of using a tablespoon instead of a teaspoon, which could lead to overdosage, the enclosed measuring device should be used or a calibrated measuring device obtained from the pharmacist.
Health care providers should recommend a calibrated device that can measure and deliver the prescribed dose accurately, and instruct caregivers to use extreme caution in measuring the dosage.
5.2 Addiction, Abuse, and Misuse Hydromorphone Hydrochloride Oral Solution and Hydromorphone Hydrochloride Tablets contain hydromorphone, a Schedule II controlled substance.
As an opioid, Hydromorphone Hydrochloride exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence ( 9 )].
Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets.
Addiction can occur at recommended dosages and if the drug is misused or abused.
Assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets, and monitor all patients receiving Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets for the development of these behaviors and conditions.
Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression).
The potential for these risks should not, however, prevent the proper management of pain in any given patient.
Patients at increased risk may be prescribed opioids such as Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets, but use in such patients necessitates intensive counseling about the risks and proper use of Hydromorphone Hydrochloride Oral Solution and Hydromorphone Hydrochloride Tablets along with intensive monitoring for signs of addiction, abuse, and misuse.
Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.
Consider these risks when prescribing or dispensing Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets.
Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see Patient Counseling Information ( 17 )].
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.
5.3 Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, even when used as recommended.
Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death.
Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status [see Overdosage ( 10 )].
Carbon dioxide (CO 2 ) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets, the risk is greatest during the initiation of therapy or following a dosage increase.
Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with and following dosage increases of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets.
To reduce the risk of respiratory depression, proper dosing and titration of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets are essential [see Dosage and Administration ( 2 )].
Overestimating the Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.
Accidental ingestion of even one dose of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets, especially by children, can result in respiratory depression and death due to an overdose of hydromorphone .
5.4 Neonatal Opioid Withdrawal Syndrome Prolonged use of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets during pregnancy can result in withdrawal in the neonate.
Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts.
Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly.
Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Use in Specific Populations ( 8.1 ), Patient Counseling Information ( 17 )].
5.5 Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Profound sedation, respiratory depression, coma, and death may result from the concomitant use of Hydromorphone Hydrochloride Oral Solution and Hydromorphone Hydrochloride Tablets with benzodiazepines or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol).
Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate.
Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone.
Because of similar pharmacological properties, it is reasonable to expect similar risk with the concomitant use of other CNS depressant drugs with opioid analgesics [see Drug Interactions ( 7 )].
If the decision is made to prescribe a benzodiazepine or other CNS depressant concomitantly with an opioid analgesic, prescribe the lowest effective dosages and minimum durations of concomitant use.
In patients already receiving an opioid analgesic, prescribe a lower initial dose of the benzodiazepine or other CNS depressant than indicated in the absence of an opioid, and titrate based on clinical response.
If an opioid analgesic is initiated in a patient already taking a benzodiazepine or other CNS depressant, prescribe a lower initial dose of the opioid analgesic, and titrate based on clinical response.
Follow patients closely for signs and symptoms of respiratory depression and sedation.
Advise both patients and caregivers about the risks of respiratory depression and sedation when Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets are used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs).
Advise patients not to drive or operate heavy machinery until the effects of concomitant use of the benzodiazepine or other CNS depressant have been determined.
Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [see Drug Interactions ( 7 ), Patient Counseling Information ( 17 )].
5.6 Life-Threatening Respiratory Depression in Patients with Chronic Pulmonary Disease or in Elderly, Cachectic, or Debilitated Patients The use of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets in patients with acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment is contraindicated.
Patients with Chronic Pulmonary Disease Hydromorphone Hydrochloride Oral Solution- or Hydromorphone Hydrochloride Tablet-treated patients with significant chronic obstructive pulmonary disease or cor pulmonale, and those with a substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression are at increased risk of decreased respiratory drive including apnea, even at recommended dosages of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets [see Warnings and Precautions ( 5.3 )].
Elderly, Cachectic, or Debilitated Patients Life-threatening respiratory depression is more likely to occur in elderly, cachectic, or debilitated patients because they may have altered pharmacokinetics or altered clearance compared to younger, healthier patients [see Warnings and Precautions ( 5.3 )].
Monitor such patients closely, particularly when initiating and titrating Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets and when Hydromorphone Hydrochloride is given concomitantly with other drugs that depress respiration [see Warnings and Precautions ( 5.3 )].
Alternatively, consider the use of non-opioid analgesics in these patients.
5.7 Adrenal Insufficiency Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.
Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure.
If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible.
If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids.
Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers.
Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency.
The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.
5.8 Severe Hypotension Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients.
There is 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 ( 7 )].
Monitor these patients for signs of hypotension after initiating or titrating the dosage of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets.
In patients with circulatory shock, Hydromorphone Hydrochloride may cause vasodilation that can further reduce cardiac output and blood pressure.
Avoid the use of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets in patients with circulatory shock.
5.9 Risks of Use in Patients with Increased Intracranial Pressure, Brain Tumors, Head Injury, or Impaired Consciousness In patients who may be susceptible to the intracranial effects of CO 2 retention (e.g., those with evidence of increased intracranial pressure or brain tumors), Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets may reduce respiratory drive, and the resultant CO 2 retention can further increase intracranial pressure.
Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy with Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets.
Opioids may also obscure the clinical course in a patient with a head injury.
Avoid the use of Hydromorphone Hydrochloride in patients with impaired consciousness or coma.
5.10 Risks of Use in Patients with Gastrointestinal Conditions Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets are contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus.
The hydromorphone in Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets may cause spasm of the sphincter of Oddi.
Opioids may cause increases in serum amylase.
Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.
5.11 Increased Risk of Seizures in Patients with Seizure Disorders The hydromorphone in Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures.
Monitor patients with a history of seizure disorders for worsened seizure control during Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets therapy.
5.12 Withdrawal Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets.
In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms [see Drug Interactions ( 7 )].
When discontinuing Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets in a physically-dependent patient, gradually taper the dosage [see Dosage and Administration ( 2.6 )].
Do not abruptly discontinue Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets in these patients.
[see Drug Abuse and Dependence ( 9.3 )].
5.13 Risks of Driving and Operating Machinery Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets may impair the mental 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 Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets and know how they will react to the medication.
5.14 Sulfites Hydromorphone Hydrochloride Oral Solution and Hydromorphone Hydrochloride Tablets contain 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 of Hydromorphone Hydrochloride Oral Solution and Hydromorphone Hydrochloride Tablets is contraindicated in patients with hypersensitivity to sulfite-containing medications .
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide).
Medication Errors Instruct patients how to measure and take the correct dose of Hydromorphone Hydrochloride, and to always use the enclosed cup when administering Hydromorphone Hydrochloride Oral Solution to ensure the dose is measured and administered accurately [see Warnings and Precautions ( 5.1 )].
If the prescribed concentration is changed, instruct patients on how to correctly measure the new dose to avoid errors which could result in accidental overdose and death.
Addiction, Abuse, and Misuse Inform patients that the use of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets, even when taken as recommended, can result in addiction, abuse, and misuse, which can lead to overdose and death [see Warnings and Precautions ( 5.2 )].
Instruct patients not to share Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets with others and to take steps to protect Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets from theft or misuse.
Life-Threatening Respiratory Depression Inform patients of the risk of life-threatening respiratory depression, including information that the risk is greatest when starting Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets or when the dosage is increased, and that it can occur even at recommended dosages [see Warnings and Precautions ( 5.3 )].
Advise patients how to recognize respiratory depression and to seek medical attention if breathing difficulties develop.
Accidental Ingestion Inform patients that accidental ingestion, especially by children, may result in respiratory depression or death [see Warnings and Precautions ( 5.3 )].
Instruct patients to take steps to store Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets securely and to dispose of unused Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets.
When Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets are no longer needed, the unused medication should be destroyed by flushing it down the toilet.
Interactions with Benzodiazepines and Other CNS Depressants Inform patients and caregivers that potentially fatal additive effects may occur if Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets are used with benzodiazepines or other CNS depressants, including alcohol, and not to use these concomitantly unless supervised by a health care provider [see Warnings and Precautions ( 5.4 ), Drug Interactions ( 7 )].
Serotonin Syndrome Inform patients that Hydromorphone Hydrochloride could cause a rare but potentially life-threatening condition resulting from concomitant administration of serotonergic drugs.
Warn patients of the symptoms of serotonin syndrome and to seek medical attention right away if symptoms develop.
Instruct patients to inform their healthcare providers if they are taking, or plan to take serotonergic medications.
[see Drug Interactions ( 7 )].
MAOI Interaction Inform patients to avoid taking Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets while using any drugs that inhibit monoamine oxidase.
Patients should not start MAOIs while taking Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets [see Drug Interactions ( 7 )].
Adrenal Insufficiency Inform patients that opioids could cause adrenal insufficiency, a potentially life-threatening condition.
Adrenal insufficiency may present with non-specific symptoms and signs such as nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure.
Advise patients to seek medical attention if they experience a constellation of these symptoms [see Warnings and Precautions ( 5.7 )].
Important Administration Instructions Instruct patients how to properly take Hydromorphone Hydrochloride.
• Advise patients to always obtain a calibrated oral syringe/dosing cup from the pharmacist for administering Hydromorphone Hydrochloride Oral Solution to ensure that the dose is measured and administered accurately [see Warnings and Precautions ( 5.1 )].
Advise patients never to use household teaspoons or tablespoons to measure Hydromorphone Hydrochloride Oral Solution.
• Advise patients not to adjust the dose of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets without consulting with a physician or other healthcare professional.
• If patients have been receiving treatment with Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets for more than a few weeks and cessation of therapy is indicated, counsel them on the importance of safely tapering the dose as abrupt discontinuation of the medication could precipitate withdrawal symptoms.
Provide a dose schedule to accomplish a gradual discontinuation of the medication [see Dosage and Administration ( 2.5 , 2.6 )].
Hypotension Inform patients that Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets may cause orthostatic hypotension and syncope.
Instruct patients how to recognize symptoms of low blood pressure and how to reduce the risk of serious consequences should hypotension occur (e.g., sit or lie down, carefully rise from a sitting or lying position) [see Warnings and Precautions ( 5.8 )].
Anaphylaxis Inform patients that anaphylaxis has been reported with ingredients contained in Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets.
Advise patients how to recognize such a reaction and when to seek medical attention [see Contraindications ( 4 ), Adverse Reactions ( 6 )].
Pregnancy Neonatal Opioid Withdrawal Syndrome : Inform female patients of reproductive potential that prolonged use of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated [see Warnings and Precautions ( 5.4 ), Use in Specific Populations ( 8.1 )].
Embryo-Fetal Toxicity : Inform female patients of reproductive potential that Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets can cause fetal harm and to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations ( 8.1 ), Warnings and Precautions ( 5.4 )] Lactation Advise nursing mothers to monitor infants for increased sleepiness (more than usual), breathing difficulties, or limpness.
Instruct nursing mothers to seek immediate medical care if they notice these signs [see Use in Specific Populations ( 8.2 )].
Infertility Inform patients that chronic use of opioids may cause reduced fertility.
It is not known whether these effects on fertility are reversible [see Use in Specific Population ( 8.3 )].
Driving or Operating Heavy Machinery Inform patients that Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets may impair the ability to perform potentially hazardous activities such as driving a car or operating heavy machinery.
Advise patients not to perform such tasks until they know how they will react to the medication [see Warnings and Precautions ( 5.13 )].
Constipation Advise patients of the potential for severe constipation, including management instructions and when to seek medical attention [see Adverse Reactions ( 6 ), Clinical Pharmacology ( 12.2 )].
Disposal of Unused Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets Advise patients to flush unused Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets down the toilet.
Distr.
by: West-Ward Pharmaceuticals Corp.
Eatontown, NJ 07724 10007362/03 Revised March 2017
DOSAGE AND ADMINISTRATION
2 • Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.
• Individualize dosing based on the severity of pain, patient response, prior analgesic experience, and risk factors for addiction, abuse, and misuse.
( 2.1 ) • Usual adult dosage of Hydromorphone Hydrochloride Oral Solution is one-half (2.5 mL) to two teaspoonsful (10 mL) (2.5 mg to 10 mg) every 3 to 6 hours.
( 2.2 ) • Usual adult starting dose for Hydromorphone Hydrochloride Tablets is 2 mg to 4 mg, orally, every 4 to 6 hours.
( 2.2 ) • Hepatic Impairment: Initiate treatment with one-fourth to one-half the usual starting dose, depending on degree of hepatic impairment.
( 2.3 ) • Renal Impairment: Initiate treatment with one-fourth to one-half the usual starting dose, depending on degree of renal impairment.
( 2.4 ) • Do not stop Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets abruptly in a physically-dependent patient.
( 2.5 ) 2.1 Important Dosage and Administration Instructions Ensure accuracy when prescribing, dispensing, and administering Hydromorphone Hydrochloride Oral Solution to avoid dosing errors due to confusion between mg and mL, which could result in accidental overdose and death.
Ensure the proper dose is communicated and dispensed.
When writing prescriptions, include both the total dose in mg and the total dose in volume.
Instruct patients to obtain a calibrated measuring cup/syringe for administering Hydromorphone Hydrochloride Oral Solution to ensure that the dose is measured and administered accurately.
Do not use household teaspoons or tablespoons to measure Hydromorphone Hydrochloride Oral Solution, as using a tablespoon instead of a teaspoon could lead to overdosage [see Warnings and Precautions ( 5.1 )].
• Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see Warnings and Precautions ( 5 )].
• Initiate the dosing regimen for each patient individually, taking into account the patient’s severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions ( 5.2 )].
• Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy and following dosage increases with Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets and adjust the dosage accordingly [see Warnings and Precautions ( 5.3 )].
2.2 Initial Dosage Initiating Treatment with Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets Hydromorphone Hydrochloride Oral Solution Initiate treatment with Hydromorphone Hydrochloride Oral Solution in a dosing range of one-half (2.5 mL) to two teaspoonsful (10 mL) (2.5 mg to 10 mg) every 3 to 6 hours as needed for pain.
Hydromorphone Hydrochloride Tablets Initiate treatment with Hydromorphone Hydrochloride Tablets in a dosing range of 2 mg to 4 mg, orally, every 4 to 6 hours.
Conversion from Other Opioids to Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets There is inter-patient variability in the potency of opioid drugs and opioid formulations.
Therefore, a conservative approach is advised when determining the total daily dosage of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets.
It is safer to underestimate a patient’s 24-hour Hydromorphone Hydrochloride dosage than to overestimate the 24-hour dosage and manage an adverse reaction due to overdose.
In general, it is safest to start Hydromorphone Hydrochloride therapy by administering half of the usual starting dose every 3 to 6 hours for Hydromorphone Hydrochloride Oral Solution; and every 4 to 6 hours for Hydromorphone Hydrochloride Tablets.
The dose of Hydromorphone Hydrochloride can be gradually adjusted until adequate pain relief and acceptable side effects have been achieved [See Dosage and Administration ( 2.4 )].
Conversion from Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets to Extended-Release Hydromorphone Hydrochloride The relative bioavailability of Hydromorphone Hydrochloride Oral Solution and Hydromorphone Hydrochloride Tablets compared to extended-release hydromorphone hydrochloride is unknown, so conversion to extended-release tablets must be accompanied by close observation for signs of excessive sedation and respiratory depression.
2.3 Dosage Modifications in Patients with Hepatic Impairment Initiate treatment with one-fourth to one-half the usual Hydromorphone Hydrochloride starting dose depending on the degree of impairment [see Use in Specific Populations ( 8.6 ), and Clinical Pharmacology ( 12.3 )].
2.4 Dosage Modifications in Patients with Renal Impairment Initiate treatment with one-fourth to one-half the usual Hydromorphone Hydrochloride starting dose depending on the degree of impairment [see Use in Specific Populations ( 8.7 ), and Clinical Pharmacology ( 12.3 )].
2.5 Titration and Maintenance of Therapy Individually titrate Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets to a dose that provides adequate analgesia and minimizes adverse reactions.
Continually reevaluate patients receiving Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [see Warnings and Precautions ( 5.2 )].
Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration.
If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets dosage.
If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage.
Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions.
For chronic pain, doses should be administered around-the-clock.
A supplemental dose of 5% to 15% of the total daily usage may be administered every two hours on an as-needed basis.
2.6 Discontinuation of Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets When a patient who has been taking Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets regularly and may be physically dependent no longer requires therapy with Hydromorphone Hydrochloride, taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal.
If the patient develops these signs and symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both.
Do not abruptly discontinue Hydromorphone Hydrochloride Oral Solution or Hydromorphone Hydrochloride Tablets in a physically dependent patient [see Warnings and Precautions ( 5.12 ), Drug Abuse and Dependence ( 9.3 )].