Hydromorphone Hydrochloride

INDICATIONS AND USAGE Hydromorphone Hydrochloride Injection is indicated for the relief of moderate to severe pain such as that due to: surgery, cancer, trauma (soft tissue and bone), biliary colic, myocardial infarction, burns, renal colic.

DOSAGE AND ADMINISTRATION The usual starting dose is 1-2 mg subcutaneously or intramuscularly every 4 to 6 hours as necessary for pain control. The dose should be adjusted according to severity of pain, as well as the patient’s underlying disease, age and size. Severe pain can usually be controlled by 3-4 mg every 4 to 6 hours as required. Patients with terminal cancer may become tolerant to narcotic analgesics and may, therefore, require higher doses for adequate pain relief. Should intravenous administration be necessary, the injection should be given very slowly (over at least 3 to 5 minutes, depending on the dose) [see WARNINGS, INTRAVENOUS USE ]. A gradual increase in dosage may be required if analgesia is inadequate, tolerance occurs or if pain severity increases. The first sign of tolerance is usually a reduced duration of effect. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

WARNINGS RESPIRATORY DEPRESSION Hydromorphone produces dose-related respiratory depression by acting directly on brain stem respiratory centers. Hydromorphone also affects centers that control respiratory rhythm and may produce irregular and periodic breathing. HEAD INJURY AND INCREASED INTRACRANIAL PRESSURE The respiratory depressant effects of hydromorphone and its capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure. Furthermore, hydromorphone produces adverse reactions which may obscure the clinical course of patients with head injuries. In such patients, hydromorphone must be used with extreme caution and only if its use is deemed essential. ACUTE ABDOMINAL CONDITIONS The administration of hydromorphone may obscure the diagnosis or clinical course of patients with acute abdominal conditions. ASTHMA AND OTHER RESPIRATORY CONDITIONS Hydromorphone should be used with extreme caution in patients having an acute asthmatic attack, patients with chronic obstructive pulmonary disease or cor pulmonale, patients having a substantially decreased respiratory reserve and patients with pre-existing respiratory depression, hypoxia or hypercapnia. In such patients, even usual therapeutic doses of narcotics may decrease respiratory drive while simultaneously increasing airway resistance to the point of apnea. INTRAVENOUS USE If necessary, hydromorphone may be given intravenously, but the injection should be given very slowly (over a period of at least 3 to 5 minutes). Rapid intravenous injection of narcotic analgesics, including hydromorphone, increases the incidence of adverse reactions; severe respiratory depression, apnea, hypotension, peripheral circulatory collapse, cardiac arrest, as well as anaphylactoid reactions, have occurred. Hydromorphone should not be administered intravenously unless a narcotic antagonist and the facilities for resuscitation and assisted or controlled respiration are immediately available. When hydromorphone is given parenterally, especially intravenously, the patient should be lying down. HYPOTENSIVE EFFECT The administration of hydromorphone may result in severe hypotension in an individual whose ability to maintain blood pressure has already been compromised by a depleted blood volume or concurrent administration of drugs such as the phenothiazines or certain anesthetics. Hydromorphone may produce orthostatic hypotension in ambulatory patients.

CONTRAINDICATIONS Hydromorphone Hydrochloride Injection is contraindicated in patients with a known hypersensitivity to hydromorphone, in the presence of an intracranial lesion associated with increased intracranial pressure and whenever ventilatory function is depressed (chronic obstructive pulmonary disease, cor pulmonale, emphysema, kyphoscoliosis, status asthmaticus). [See WARNINGS . ] Narcotic analgesics, including hydromorphone, are contraindicated in premature infants or during labor when delivery of a premature infant is anticipated.

DRUG INTERACTIONS Hydromorphone should be administered cautiously and in reduced dosage to avoid additive effects when other central nervous system depressants including other narcotic analgesics, general anesthetics, phenothiazines, tricyclic antidepressants, sedative-hypnotics or other CNS depressants (including alcohol) are given concomitantly. Whenever concomitant therapy with MAO inhibitors and narcotic analgesics, including hydromorphone is to be used, an initial small test dose is advisable to allow observation of excessive narcotic effects or MAOI interaction.

PREGNANCY Teratogenic Effects - Pregnancy Category C. Hydromorphone has been shown to be teratogenic in golden hamsters with a minimal effective teratogenic dose of 19 mg/kg, when given in doses 600 times the usual therapeutic dose in humans. There are no adequate and well-controlled studies in pregnant women. Hydromorphone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nonteratogenic Effects. Dependence has been reported in newborns whose mothers took opiates regularly during pregnancy. The withdrawal signs include irritability and excessive crying, tremors, hyperactive reflexes, increased respiratory rate, increased stools, sneezing, yawning, vomiting and fever. Signs usually appear during the first few days of life.

ADVERSE REACTIONS The major hazards of hydromorphone, as with other narcotic analgesics, are respiratory depression and, to a lesser degree, circulatory depression; respiratory arrest, shock and cardiac arrest have occurred, particularly with overdosage or rapid intravenous administration. Anaphylactoid reactions have been reported when phenanthrene alkaloids of opium are administered intravenously. CENTRAL NERVOUS SYSTEM: Sedation, drowsiness, mental clouding, headache, tremor, visual disturbances, weakness, agitation, lethargy, impairment of mental and physical performance, uncoordinated muscle movements, anxiety, fear, euphoria, dysphoria, dizziness, psychological dependence and mood changes. GASTROINTESTINAL SYSTEM: Nausea and vomiting occur more frequently in ambulatory than in recumbent patients. Hydromorphone may produce constipation, biliary tract spasm and can increase intraluminal pressure which may endanger surgical anastomosis. Patients with chronic ulcerative colitis may experience increased colonic motility; in patients with acute ulcerative colitis, toxic dilatation has been reported with narcotics. CARDIOVASCULAR SYSTEM: Circulatory depression, peripheral circulatory collapse and cardiac arrest have occurred after rapid intravenous injection. Orthostatic hypotension and fainting may occur, especially if a patient stands up suddenly after receiving an injection of hydromorphone. Additionally, hydromorphone may cause tachycardia, bradycardia and palpitations. GENITOURINARY SYSTEM: Oliguria, ureteral spasm, spasm of vesical sphincters and urinary retention have been reported. RESPIRATORY DEPRESSION: Hydromorphone produces dose-related respiratory depression by acting directly on brain stem respiratory centers. Hydromorphone also affects centers that control respiratory rhythm and may produce irregular and periodic breathing. If significant respiratory depression occurs, it may be antagonized by the use of naloxone hydrochloride. In patients who are physically dependent, small doses of naloxone may be sufficient not only to antagonize respiratory depression but also to precipitate withdrawal phenomena. The dose of naloxone should, therefore, be adjusted accordingly in such patients. Since the duration of action of hydromorphone 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. ALLERGIC: Allergic reactions to opiates occur infrequently; pruritus, urticaria and other skin rashes are most common. Anaphylactoid reactions have been reported following intravenous administration of opiates. OTHER: Opiate-induced histamine release may be responsible for the flushing of the face, sweating and pruritus often seen with these drugs. Wheals and urticaria at the site of injection are probably related to histamine release. Local tissue irritation, pain and induration have been reported following repeated subcutaneous injection.