Morphine sulfate may be habit forming. (See DRUG ABUSE AND DEPENDENCE.) Overdoses may cause respiratory depression, coma and death.
DURAMORPH administration should be limited to use by those familiar with the management of respiratory depression. Rapid intravenous administration may result in chest wall rigidity.
Prior to any epidural or intrathecal drug administration, the physician should be familiar with patient conditions (such as infection at the injection site, bleeding diathesis, anticoagulant therapy, etc.) which call for special evaluation of the benefit versus risk potential.
In the case of epidural or intrathecal administration, DURAMORPH should be administered by or under the direction of a physician experienced in the techniques and familiar with the patient management problems associated with epidural or intrathecal drug administration. Because epidural administration has been associated with less potential for immediate or late adverse effects than intrathecal administration, the epidural route should be used whenever possible.
SEVERE RESPIRATORY DEPRESSION UP TO 24 HOURS FOLLOWING EPIDURAL OR INTRATHECAL ADMINISTRATION HAS BEEN REPORTED.
| BECAUSE OF THE RISK OF SEVERE ADVERSE EFFECTS WHEN THE EPIDURAL OR INTRATHECAL ROUTE OF ADMINISTRATION IS EMPLOYED, PATIENTS MUST BE OBSERVED IN A FULLY EQUIPPED AND STAFFED ENVIRONMENT FOR AT LEAST 24 HOURS AFTER THE INITIAL DOSE. |
THE FACILITY MUST BE EQUIPPED TO RESUSCITATE PATIENTS WITH SEVERE OPIATE OVERDOSAGE, AND THE PERSONNEL MUST BE FAMILIAR WITH THE USE AND LIMITATIONS OF SPECIFIC NARCOTIC ANTAGONISTS (NALOXONE, NALTREXONE) IN SUCH CASES.
Tolerance and Myoclonic Activity
PATIENTS SOMETIMES MANIFEST UNUSUAL ACCELERATION OF NEURAXIAL MORPHINE REQUIREMENTS, WHICH MAY CAUSE CONCERN REGARDING SYSTEMIC ABSORPTION AND THE HAZARDS OF LARGE DOSES; THESE PATIENTS MAY BENEFIT FROM HOSPITALIZATION AND DETOXIFICATION. TWO CASES OF MYOCLONIC-LIKE SPASM OF THE LOWER EXTREMITIES HAVE BEEN REPORTED IN PATIENTS RECEIVING MORE THAN 20 MG/DAY OF INTRATHECAL MORPHINE. AFTER DETOXIFICATION, IT MIGHT BE POSSIBLE TO RESUME TREATMENT AT LOWER DOSES, AND SOME PATIENTS HAVE BEEN SUCCESSFULLY CHANGED FROM CONTINUOUS EPIDURAL MORPHINE TO CONTINUOUS INTRATHECAL MORPHINE. REPEAT DETOXIFICATION MAY BE INDICATED AT A LATER DATE. THE UPPER DAILY DOSAGE LIMIT FOR EACH PATIENT DURING CONTINUING TREATMENT MUST BE INDIVIDUALIZED.
Control of pain by neuraxial opiate delivery is always accompanied by considerable risk to the patients and requires a high level of skill to be successfully accomplished. The task of treating these patients must be undertaken by experienced clinical teams, well-versed in patient selection, evolving technology and emerging standards of care. For safety reasons, it is recommended that administration of DURAMORPH by the epidural or intrathecal routes be limited to the lumbar area. Intrathecal use has been associated with a higher incidence of respiratory depression than epidural use.
Seizures may result from high doses. Patients with known seizure disorders should be carefully observed for evidence of morphine-induced seizure activity.
Use in Patients with Increased Intracranial Pressure or Head Injury
DURAMORPH should be used with extreme caution in patients with head injury or increased intracranial pressure. Pupillary changes (miosis) from morphine may obscure the existence, extent and course of intracranial pathology. High doses of neuraxial morphine may produce myoclonic events (see WARNINGS and ADVERSE REACTIONS). Clinicians should maintain a high index of suspicion for adverse drug reactions when evaluating altered mental status or movement abnormalities in patients receiving this modality of treatment.
Use in Chronic Pulmonary Disease
Care is urged in using this drug in patients who have a decreased respiratory reserve (e.g., emphysema, severe obesity, kyphoscoliosis or paralysis of the phrenic nerve). DURAMORPH should not be given in cases of chronic asthma, upper airway obstruction or in any other chronic pulmonary disorder without due consideration of the known risk of acute respiratory failure following morphine administration in such patients.
Use in Hepatic or Renal Disease
The elimination half-life of morphine may be prolonged in patients with reduced metabolic rates and with hepatic and/or renal dysfunction. Hence, care should be exercised in administering DURAMORPH epidurally to patients with these conditions, since high blood morphine levels, due to reduced clearance, may take several days to develop.
Use in Biliary Surgery or Disorders of the Biliary Tract
As significant morphine is released into the systemic circulation from neuraxial administration, the ensuing smooth muscle hypertonicity may result in biliary colic.
Use with Disorders of the Urinary System
Initiation of neuraxial opiate analgesia is frequently associated with disturbances of micturition, especially in males with prostatic enlargement. Early recognition of difficulty in urination and prompt intervention in cases of urinary retention is indicated.
Use in Ambulatory Patients
Patients with reduced circulating blood volume, impaired myocardial function or on sympatholytic drugs should be monitored for the possible occurrence of orthostatic hypotension, a frequent complication in single-dose neuraxial morphine analgesia.
Use with Other Central Nervous System Depressants
The depressant effects of morphine are potentiated by the presence of other CNS depressants such as alcohol, sedatives, antihistaminics or psychotropic drugs. Use of neuroleptics in conjunction with neuraxial morphine may increase the risk of respiratory depression.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Morphine is without known carcinogenic or mutagenic effects and is not known to impair fertility at non-narcotic doses in animals, but studies of the carcinogenic and mutagenic potential or the effect on fertility of DURAMORPH have not been conducted.
Teratogenic Effects—Pregnancy Category C
Morphine sulfate is not teratogenic in rats at 35 mg/kg/day (thirty-five times the usual human dose) but does result in increased pup mortality and growth retardation at doses that narcotize the animal (> 10 mg/kg/day, ten times the usual human dose). DURAMORPH should only be given to pregnant women when no other method of controlling pain is available and means are at hand to manage the delivery and perinatal care of the opiate-dependent infant.
Infants born to mothers who have been taking morphine chronically may exhibit withdrawal symptoms.
Labor and Delivery
Intravenous morphine readily passes into the fetal circulation and may result in respiratory depression in the neonate. Naloxone and resuscitative equipment should be available for reversal of narcotic-induced respiratory depression in the neonate. In addition, intravenous morphine may reduce the strength, duration and frequency of uterine contraction resulting in prolonged labor.
Epidurally and intrathecally administered morphine readily passes into the fetal circulation and may result in respiratory depression of the neonate. Controlled clinical studies have shown that epidural administration has little or no effect on the relief of labor pain.
Morphine is excreted in maternal milk. Effects on the nursing infant are not known.
Adequate studies, to establish the safety and effectiveness of spinal morphine in pediatric patients, have not been performed, and usage in this population is not recommended.
The pharmacodynamic effects of neuraxial morphine in the elderly are more variable than in the younger population. Patients will vary widely in the effective initial dose, rate of development of tolerance and the frequency and magnitude of associated adverse effects as the dose is increased. Initial doses should be based on careful clinical observation following “test doses”, after making due allowances for the effects of the patient’s age and infirmity on his/her ability to clear the drug, particularly in patients receiving epidural morphine.
Elderly patients may be more susceptible to respiratory depression and/or respiratory arrest following administration of morphine.