Dilaudid-HP Lyophilized Powder 250 mg- Abbott - Marketed Lyophilized Drug Products

DILAUDID-HP should be used 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.
Head Injury and Increased Intracranial Pressure: The respiratory depressant effects of DILAUDID-HP with carbon dioxide retention and secondary elevation of cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions, or preexisting increase in intracranial pressure. Opioid analgesics including DILAUDID-HP may produce effects which can obscure the clinical course and neurologic signs of further increase in pressure in patients with head injuries.
Hypotensive Effect: Opioid analgesics, including DILAUDID-HP, may cause severe hypotension in an individual whose ability to maintain his blood pressure has already been compromised by a depleted blood volume, or a concurrent administration of drugs such as phenothiazines or general anesthetics (see also PRECAUTIONS -- Drug Interactions ). DILAUDlD-HP may produce orthostatic hypotension in ambulatory patients.
DILAUDlD-HP should be administered with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure.
Sulfites: Contains sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
PRECAUTIONS
General: Because of its high concentration, the delivery of precise doses of DILAUDID-HP may be difficult if low doses of hydromorphone are required. Therefore, DILAUDID-HP should be used only if the amount of hydromorphone required can be delivered accurately with this formulation.
Special Risk Patients : In general, opioids 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 function; 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; or kyphoscoliosis or following gastrointestinal surgery.
In the case of DILAUDID-HP, however, the patientis presumed to be receiving an opioid to which he or she exhibits tolerance and the initial dose of DILAUDID-HP selected should be estimated based on the relative potency of hydromorphone and the opioid previously used by the patient. (see DOSAGE AND ADMINISTRATION ).
The administration of opioid analgesics including DILAUDID-HP may obscure the diagnosis 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 Biliary Surgery: Opioid analgesics including DILAUDID-HP, 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.
Use in Drug and Alcohol Dependent Patients: DILAUDID-HP 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 DILAUDID-HP in combination with other CNS depressant drugs can result in serious risk to the patient.
Drug Interactions: The concomitant use of other central nervous system depressants including sedatives or hypnotics, general anesthetics, phenothiazines, tranquilizers and alcohol may produce additive depressant effects. Respiratory depression, hypotension and profound sedation or coma may occur. When such combined therapy is contemplated, the dose of one or both agents should be reduced. Opioid analgesics, including DILAUDID-HP may enhance the action of neuromuscular blocking agents and produce an increased degree of respiratory depression.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Animal carcinogenicity studies have not been performed with DILAUDID.
DILAUDID was not mutagenic in the in vitro Ames reverse mutation assay, in the in vitro chromosome aberration assay in human lymphocytes, or in the in vivo mouse bone marrow micronucleus test.
Fertility in male or female rats was not affected after daily oral administration at doses up to 7 mg/kg/day (41 mg/m 2 ). DILAUDID was dosed from 4 weeks prior to mating in males and 2 weeks prior to mating in females.
PREGNANCY-CATEGORY C:
Human: There are no well-controlled studies in women. Reports based on marketing experience do not identify any specific teratogenic risks following routine (short-term) clinical use. Although there is no clearly defined risk, such reports do not exclude the possibility of infrequent or subtle damage to the human fetus. DILAUDID-HP should be used in pregnant women only when clearly needed (see Labor and Delivery and DRUG ABUSE AND DEPENDENCE ).
Animal: Neither embryo-fetal toxicity nor teratogenic effects were observed following administration of DILAUDID at oral doses up to 7 mg/kg/day (41 mg/m 2 ) in rats from day 6 to day 17 of gestation and up to 25 mg/kg/day (315 mg/m 2 ) in rabbits from day 6 to day 20 of gestation.
Literature reports of hydromorphone hydrochloride administration to pregnant Syrian hamsters show that DILAUDID is teratogenic at a dose of 20 mg/kg which is 600 times the human dose. A maximal teratogenic effect (50% of fetuses affected) in the Syrian hamster was observed at a dose of 125 mg/kg.
Nonteratogenic effects: Babies born to mothers who have been taking opoiods regularly prior to delivery will be physically dependent. The withdrawal signs include irritability and excessive crying, tremors, hyperactive reflexes, increased respiratory rate, increased stools, sneezing, yawning, vomiting, and fever. The intensity of the syndrome does not always correlate with the duration of maternal opioid use or dose. There is no consensus on the best method of managing withdrawal. Approaches to the treatment of this syndrome have included supportive care and, when indicated, drugs such as paregoric or phenobarbital.
Labor and Delivery: DILAUDID-HP is contraindicated in Labor and Delivery (see CONTRAINDICATIONS ).
Nursing Mothers: 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-HP since it, and other drugs in this class, may be excreted in the milk.
Pediatric Use: Safety and effectiveness have not been established.
Geriatric Use: Clinical studies of DILAUDID 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. (see PRECAUTIONS ).
ADVERSE REACTIONS
The adverse effects of DILAUDID-HP are similar to those of other opioid analgesics, and represent established pharmacological effects of the drug class. The major hazards include respiratory depression and apnea. To a lesser degree, circulatory depression, respiratory arrest, shock and cardiac arrest have occurred.
The most frequently observed adverse effects are lightheadedness, dizziness, sedation, nausea, vomiting, and sweating. These effects seem to be more prominent in ambulatory patients and in those not experiencing severe pain. Syncopal reactions and related symptoms in ambulatory patients may be alleviated if the patient lies down.
Less Frequently Observed with Opioid Analgesics:
General and CNS: Dysphoria, euphoria, weakness, headache, agitation, tremor, uncoordinated muscle movements, alterations of mood (nervousness, apprehension, depression, floating feelings, dreams), muscle rigidity, paresthesia, muscle tremor, blurred vision, nystagmus, diplopia and miosis, transient hallucinations * and disorientation, visual disturbances, insomnia and increased intracranial pressure may occur.
*Hallucinations, although unusual with pure agonist opioids, have been observed in one patient following both a 6 mg and a 4 mg DILAUDID-HP (hydromorphone hydrochloride) dose. However, the patient was receiving several concomitant medications during the second episode and a causal relationship cannot be established.
Cardiovascular: Flushing of the face, chills, tachycardia, bradycardia, palpitation, faintness, syncope, hypotension and hypertension have been reported.
Respiratory: Bronchospasm and laryngospasm have been known to occur.
Gastrointestinal: Dry mouth, constipation, biliary tract spasm, ileus anorexia, diarrhea, cramps and taste alterations have been reported.
Genitourinary: Urinary retention or hesitancy, and antidiuretic effects have been reported.
Dermatologic: Pruritis, urticaria, other skin rashes, wheal and flare over the vein with intravenous injection, and diaphoresis have been reported with opioid analgesics.
Other: In clinical trials, neither local tissue ir