Dilaudid (Hydromorphone Hydrochloride) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

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/m²). DILAUDID was dosed from 4 weeks prior to mating in males and 2 weeks prior to mating in females.

Pregnancy

Pregnancy Category C

Neither embryo-fetal toxicity nor teratogenic effects were observed following administration of DILAUDID at oral doses up to 7 mg/kg/day (41 mg/m²) in rats from Day 6 to Day 17 of gestation and up to 25 mg/kg/day (315 mg/m²) 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 (738 mg/m²).

There are no well-controlled studies in women. Hydromorphone is known to cross placental membranes. DILAUDID ORAL LIQUID and DILAUDID 8 mg TABLETS should be used in pregnant women only if the potential benefit justifies the potential risk to the fetus (see Labor and Delivery and DRUG ABUSE AND DEPENDENCE).

OVERDOSAGE

Serious overdosage with DILAUDID ORAL LIQUID and DILAUDID 8 mg TABLETS is characterized by respiratory depression, somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and sometimes bradycardia and hypotension. In serious overdosage, particularly following intravenous injection, apnea, circulatory collapse, cardiac arrest and death may occur.

In the treatment of overdosage, primary attention should be given to the reestablishment of adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled ventilation. A potentially serious oral ingestion, if recent, should be managed with gut decontamination. In unconscious patients with a secure airway, instill activated charcoal (30-100 g in adults, 1-2 g/kg in infants) via a nasogastric tube. A saline cathartic or sorbitol may be added to the first dose of activated charcoal.

Opioid-Tolerant Patient

Since tolerance to the respiratory and CNS depressant effects of opioids develops concomitantly with tolerance to their analgesic effects, serious respiratory depression due to an acute overdose is unlikely to be seen in opioid-tolerant patients receiving the usual therapeutic dosage of DILAUDID ORAL LIQUID and DILAUDID 8 mg TABLETS for chronic pain.

NOTE: In such an individual who is physically dependent on opioids, administration of the usual dose of an opioid antagonist will precipitate an acute withdrawal syndrome. The severity will depend on the degree of physical dependence and the dose of the antagonist administered. Use of an opioid antagonist should be reserved for cases where such treatment is clearly needed. If necessary to treat serious respiratory depression in the physically-dependent patient, the opioid antagonist should be administered with extreme care and by titration, using fractional (one fifth to one tenth) doses of the antagonist.

Non-Tolerant Patient

The opioid antagonist, naloxone, is a specific antidote against respiratory depression which may result from overdosage, or unusual sensitivity to DILAUDID ORAL LIQUID and DILAUDID 8 mg TABLETS. A dose of naloxone (usually given as a test dose of 0.4 mg, followed by up to 2.0 mg if needed) should be administered intravenously, if possible, simultaneously with respiratory resuscitation. The dose can be repeated in 3 minutes. Naloxone should not be administered in the absence of clinically significant respiratory or circulatory depression. Naloxone should be administered cautiously to persons who are known, or suspected to be physically dependent on DILAUDID ORAL LIQUID and DILAUDID 8 mg TABLETS (see Opioid-Tolerant Patient). In such cases, an abrupt or complete reversal of narcotic effects may precipitate an acute abstinence syndrome. Since the duration of action of DILAUDID ORAL LIQUID and DILAUDID 8 mg TABLETS may exceed that of the antagonist, the patient should be kept under continued surveillance; repeated doses of the antagonist may be required to maintain adequate respiration. Apply other supportive measures when indicated.

Supportive measures (including oxygen, vasopressors) should be employed in the management of circulatory shock and pulmonary edema accompanying overdose as indicated. Cardiac arrest or arrhythmias may require cardiac massage or defibrillation.

CONTRAINDICATIONS

DILAUDID ORAL LIQUID and DILAUDID 8 mg TABLETS are contraindicated in: patients with known hypersensitivity to hydromorphone, patients with respiratory depression in the absence of resuscitative equipment, and in patients with status asthmaticus. DILAUDID ORAL LIQUID and DILAUDID 8 mg TABLETS are also contraindicated for use in obstetrical analgesia.