"Nov. 2, 2012 -- Safety steps taken in the wake of the fungal meningitis outbreak have worsened drug shortages, raising questions about whether the U.S. must choose between the safety and the availability of crucial medicines.
Risk of Medication Errors
DILAUDID-HP INJECTION is a 10 mg/mL concentrated solution of hydromorphone, and is intended for use in opioid-tolerant patients only. Patients considered opioid tolerant are those who are taking at least 60 mg oral morphine/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 one week or longer.
Do not confuse DILAUDID-HP INJECTION with standard parenteral formulations of DILAUDID INJECTION (1 mg/mL, 2 mg/mL, 4 mg/mL) or other opioids, as overdose and death could result.
Morphine does not convert to hydromorphone on a mg per mg basis. Use Table 1 when converting a patient from morphine to hydromorphone to avoid errors that can lead to overdose or death.
Respiratory depression is the chief hazard of DILAUDID INJECTION and DILAUDIDHP INJECTION. Respiratory depression occurs most frequently in the elderly, in the debilitated, and in those suffering from conditions accompanied by hypoxia or hypercapnia, or upper airway obstruction, in whom even moderate therapeutic doses may dangerously decrease pulmonary ventilation. Respiratory depression is also a particular problem following large initial doses in non opioid-tolerant patients or when opioids are given in conjunction with other agents that depress respiration.
Use DILAUDID INJECTION and DILAUDID-HP INJECTION with extreme caution in patients with chronic obstructive pulmonary disease or cor pulmonale, patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression. In such patients, even usual therapeutic doses of opioid analgesics may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea. Consider using non-opioid analgesics, and administer DILAUDID only under careful medical supervision at the lowest effective dose in such patients.
Misuse, Abuse and Diversion of Opioids
DILAUDID INJECTION and DILAUDID-HP INJECTION contain hydromorphone, an opioid agonist with an abuse liability similar to morphine, and a Schedule II, controlled substance. Hydromorphone has the potential for being abused, is sought by drug abusers and people with addiction disorders, and is subject to criminal diversion. Diversion of Schedule II products is an act subject to criminal penalty.
Abuse of DILAUDID INJECTION and DILAUDID-HP INJECTION, poses a hazard of overdose and death. This risk is increased with concurrent abuse of alcohol or other substances. Schedule II opioid agonists have the highest potential for abuse and risk of fatal respiratory depression.
DILAUDID INJECTION and DILAUDID-HP INJECTION can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing DILAUDID INJECTION and DILAUDID-HP INJECTION in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse or diversion.
Concerns about abuse, addiction, and diversion should not prevent the proper management of pain. 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.
Interactions with Alcohol and other CNS Depressants
The concurrent use of DILAUDID INJECTION or DILAUDID-HP INJECTION with other central nervous system (CNS) depressants, including but not limited to, other opioids, illicit drugs, sedatives, hypnotics, general anesthetics, phenothiazines, muscle relaxants, other tranquilizers, and alcohol, increases the risk of respiratory depression, hypotension, and profound sedation, potentially resulting in coma or death. Use with caution and in reduced dosages in patients taking CNS depressants.
Neonatal Withdrawal Syndrome
Infants born to mothers physically dependent on DILAUDID INJECTION or DILAUDID-HP INJECTION will also be physically dependent and may exhibit signs of withdrawal. 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. Neonatal opioid withdrawal syndrome may be life threatening and should be treated according to protocols developed by neonatology experts [see Drug Abuse And Dependence].
Use in Increased Intracranial Pressure or Head Injury
The respiratory depressant effects of DILAUDID INJECTION and DILAUDID-HP INJECTION promote carbon dioxide retention which results in elevation of cerebrospinal fluid pressure. This increase in intracranial pressure may be markedly exaggerated in the presence of head injury, intracranial lesions, or other conditions that predispose patients to increased intracranial pressure.
DILAUDID INJECTION and DILAUDID-HP INJECTION may produce effects on pupillary response and consciousness which can obscure the clinical course and neurologic signs of further increase in pressure in patients with head injuries.
DILAUDID INJECTION and DILAUDID-HP INJECTION may cause severe hypotension in patients whose ability to maintain blood pressure is compromised by a depleted blood volume, or a concurrent administration of drugs such as phenothiazines, general anesthetics, or other agents which compromise vasomotor tone [see DRUG INTERACTIONS].
DILAUDID INJECTION and DILAUDID-HP INJECTION may produce orthostatic hypotension in ambulatory patients.
DILAUDID INJECTION and DILAUDID-HP INJECTION 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 in Pancreatic/Biliary Tract Disease and Other Gastrointestinal Conditions
Use DILAUDID INJECTION and DILAUDID-HP with caution in patients who are at risk of developing ileus.
Use DILAUDID INJECTION and DILAUDID-HP INJECTION with caution in patients with biliary tract disease, including acute pancreatitis, as hydromorphone may cause spasm of the sphincter of Oddi and diminish biliary and pancreatic secretions.
Special Risk Patients
Give DILAUDID INJECTION and DILAUDID-HP INJECTION with caution and the initial dose should be reduced in the elderly or debilitated and those with severe impairment of hepatic, pulmonary or renal function; myxedema or hypothyroidism; adrenocortical insufficiency (e.g., Addison's Disease); CNS depression or coma; toxic psychoses; prostatic hypertrophy or urethral stricture; acute alcoholism; delirium tremens; or kyphoscoliosis associated with respiratory depression.
The administration of opioid analgesics including DILAUDID INJECTION and DILAUDID-HP INJECTION may aggravate preexisting convulsions in patients with convulsive disorders.
DILAUDID INJECTION and DILAUDID-HP INJECTION, as with other opioids, may aggravate convulsions in patients with convulsive disorders, and may induce or aggravate seizures in some clinical settings.
Reports of mild to severe seizures and myoclonus have been reported in severely compromised patients, administered high doses of parenteral hydromorphone.
Use in Drug and Alcohol Dependent Patients
Use DILAUDID INJECTION and DILAUDID-HP INJECTION 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 DILAUDID INJECTION or DILAUDID-HP INJECTION in combination with other CNS depressant drugs can result in serious risk to the patient.
DILAUDID INJECTION and DILAUDID-HP INJECTION contain hydromorphone, an opioid with no approved use in the management of addiction disorders. Its proper usage in individuals with drug or alcohol dependence, either active or in remission, is for the management of pain requiring opioid analgesia.
Use in Ambulatory Patients
DILAUDID INJECTION and DILAUDID-HP INJECTION 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. DILAUDID INJECTION and DILAUDID-HP INJECTION may produce orthostatic hypotension in ambulatory patients.
DILAUDID INJECTION may be given intravenously, but the injection should be given very slowly. Rapid intravenous injection of opioid analgesics increases the possibility of side effects such as hypotension and respiratory depression [see DOSAGE AND ADMINSTRATION].
Carcinogenesis, Mutagenesis, Impairment of Fertility
Long term studies in animals to evaluate the carcinogenic potential of hydromorphone have not been conducted.
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
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 3-fold higher than the human dose of 24 mg DILAUDID INJECTION (4 mg every 4 hours), on a body surface area basis.
Use In Specific Populations
Teratogenic Effects - Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. Hydromorphone crosses the placenta. DILAUDID INJECTION or DILAUDID-HP INJECTION should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
No effects on teratogenicity or embryotoxicity were observed in pregnant rats given oral doses up to 7 mg/kg/day which is 3-fold higher than the human dose of 24 mg DILAUDID INJECTION (4 mg every 4 hours), on a body surface area basis. Hydromorphone administration to pregnant Syrian hamsters and CF-1 mice during major organ development revealed teratogenic effects 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 8-10), doses ≥ 19 mg/kg of hydromorphone produced skull malformations (exencephaly and cranioschisis). In CF-1 mice, continuous infusion of hydromorphone ( > 15 mg/kg over 24 hours) via implanted osmotic pumps during organogenesis (gestation days 7-10) produced 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). The malformations and variations observed in the hamsters and mice were observed at doses approximately 6-fold and 3fold higher, respectively, than the human dose of 24 mg DILAUDID INJECTION (4 mg every 4 hours), on a body surface area basis.
Labor and Delivery
DILAUDID should be used with caution during labor. Opioids cross the placenta and may produce respiratory depression and physiologic effects in neonates. Sinusoidal fetal heart rate patterns may occur with the use of opioid analgesics.
Occasionally, opioid analgesics, including DILAUDID INJECTION and DILAUDID-HP INJECTION, may 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 dilatation, which tends to shorten labor.
Opioid analgesics, including DILAUDID INJECTION and DILAUDID-HP INJECTION, may cause respiratory depression in the newborn. Closely observe neonates whose mothers received opioid analgesics during labor for signs of respiratory depression. Have a specific opioid antagonist, such as naloxone or nalmefene, available for reversal of opioid-induced respiratory depression in the neonate.
Neonates whose mothers have been taking opioids chronically may also exhibit withdrawal signs, either at birth or in the nursery, because they have developed physical dependence. This is not, however, synonymous with addiction [see Drug Abuse And Dependence]. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening and should be treated according to protocols developed by neonatology experts [see WARNINGS AND PRECAUTIONS]. The effect of DILAUDID, if any, on the later growth, development, and functional maturation of the child is unknown.
Low levels of opioid analgesics have been detected in human milk. As a general rule, nursing should not be undertaken while a patient is receiving DILAUDID INJECTION or DILAUDID-HP INJECTION since it, and other drugs in this class, may be excreted in the milk.
The safety and effectiveness of DILAUDID INJECTION and DILAUDID-HP INJECTION in pediatric patients has not been established.
Clinical studies of DILAUDID INJECTION and DILAUDID-HP INJECTION did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, 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 in elderly or debilitated patients, usually the result of large initial doses in non-opioid-tolerant patients. Titration in these patients should proceed cautiously [see DOSAGE AND ADMINISTRATION and WARNINGS AND PRECAUTIONS].
The pharmacokinetics of hydromorphone following an oral administration of hydromorphone at a single 4 mg dose (2 mg hydromorphone immediate-release tablets) are affected by renal impairment. Mean exposure to hydromorphone (Cmax and AUC0-∝) is increased by 2-fold in patients with moderate (CLcr = 40 - 60 mL/min) renal impairment and increased by 4-fold in patients with severe (CLcr < 30 mL/min) renal impairment compared with normal subjects (CLcr > 80 mL/min). In addition, in patients with severe renal impairment, hydromorphone appeared to be more slowly eliminated with a longer terminal elimination half-life (40 hr) compared to patients with normal renal function (15 hr). Start patients with renal impairment on one-fourth to one-half the usual starting dose depending on the degree of impairment. Patients with renal impairment should be closely monitored during dose titration [see CLINICAL PHARMACOLOGY].
The pharmacokinetics of hydromorphone following an oral administration of hydromorphone at a single 4 mg dose (2 mg hydromorphone immediate-release tablets) are affected by hepatic impairment. Mean exposure to hydromorphone (Cmax and AUC∞) is increased 4-fold in patients with moderate (Child-Pugh Group B) hepatic impairment compared with subjects with normal hepatic function. Due to increased exposure of hydromorphone, patients with moderate hepatic impairment should be started at one-fourth to one-half the recommended starting dose depending on the degree of hepatic dysfunction and closely monitored during dose titration. The pharmacokinetics of hydromorphone in patients with severe hepatic impairment has not been studied. A further increase in Cmax and AUC of hydromorphone in this group is expected and should be taken into consideration when selecting a starting dose [see CLINICAL PHARMACOLOGY].
Last reviewed on RxList: 8/12/2011
This monograph has been modified to include the generic and brand name in many instances.
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