WARNINGS
IMPAIRED RESPIRATION:
Respiratory depression is the chief hazard of all morphine preparations. Respiratory depression occurs more frequently in the elderly and debilitated patients, as well as in those suffering from conditions accompanied by hypoxia or hypercapnia when even moderate therapeutic doses may dangerously decrease pulmonary ventilation.
Morphine should be used with extreme caution in patients who have a decreased respiratory reserve (e.g., emphysema, severe obesity, kyphoscoliosis, or paralysis of the phrenic nerve). ORAMORPH SR 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.
DRUG ABUSE AND DEPENDENCE - CONTROLLED SUBSTANCE:
Morphine sulfate is a Schedule II narcotic under the United States Controlled Substance Act (21 U.S.C. 801-886).
Morphine is the most commonly cited prototype for narcotic substances that possess an addiction-forming or addiction-sustaining liability. A patient may be at risk for developing a dependence to morphine if used improperly or for overly long periods of time. As with all potent opioids which are μ-agonists, tolerance as well as psychological and physical dependence to morphine may develop irrespective of the route of administration (oral, intravenous, intramuscular, intrathecal, or epidural). Individuals with a prior history of opioid or other substance abuse or dependence, being more apt to respond to euphorogenic and reinforcing properties of morphine, would be considered to be at greater risk.
Care must be taken to avert withdrawal symptoms when morphine is discontinued abruptly or upon administration of a narcotic antagonist.
PRECAUTIONS
General Precautions:
Selection of patients for treatment with ORAMORPH SR should be governed by the same principles that apply to the use of morphine or other potent opioid analgesics. Narcotic analgesics are drugs that have a narrow therapeutic index in the old, the sick, and the infirm, i.e., the very population in which their use is indicated. Physicians should individualize treatment with ORAMORPH SR in every case, weighing the need for analgesia against the risks of serious or fatal reactions to the drug.
Use in Patients with Increased Intracranial Pressure or with Head Injury:
ORAMORPH SR should be used with extreme caution in patients with increased intracranial pressure or with head injury. The respiratory depressant effects of morphine (increased pCO2) may result in elevation of cerebrospinal fluid pressure and may thus be markedly exaggerated in the presence of head injury, other intracranial lesions, or a pre-existing increased intracranial pressure. Morphine produces effects which may obscure neurologic signs of further increases in pressure in patients with head injuries. Pupillary changes (miosis), associated with morphine, may conceal the existence, extent, and course of intracranial pathology.
Use in Hepatic or Renal Disease:
The clearance of morphine may be reduced in patients with hepatic dysfunction, while the clearance of its metabolites may be decreased in renal dysfunction. This will be manifested by both a prolonged elimination half-life and the accumulation of levels of either morphine or its metabolites in excess of those produced in normals, with the potential for an increase of adverse effects (see WARNINGS and ADVERSE REACTIONS). These changes in morphine pharmacodynamics, in patients with hepatic or renal dysfunctions, should be considered when adjusting the dose and dosage intervals, taking also into account the slow-release character of ORAMORPH SR.
Drug Interactions:
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 oral morphine may increase the risk of respiratory depression, hypotension and profound sedation or coma.
Interaction with Mixed Agonist/Antagonist Opioid Analgesics:
Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, butorphanol, or buprenorphine) should NOT be administered to patients who have received or are receiving a course of therapy with a pure opioid agonist analgesic. In these patients, the mixed agonist/antagonist may alter the analgesic effect or may precipitate withdrawal symptoms.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Studies of morphine sulfate in animals to evaluate the drug's carcinogenic and mutagenic potential or the effect on fertility have not been conducted.
Pregnancy:
Teratogenic Effects - Category C: There are no well-controlled studies in women, but marketing experience does not include any evidence of adverse effects on the fetus following routine (short-term) clinical use of morphine sulfate products. Although there is no clearly defined risk, such experience cannot exclude the possibility of infrequent or subtle damage to the human fetus.
ORAMORPH SR should be used in pregnant women only when clearly needed. (See also: PRECAUTIONS: Labor and Delivery, and DRUG ABUSE AND DEPENDENCE CONTROLLED SUBSTANCE.)
Nonteratogenic Effects:
Infants born from mothers who have been taking morphine chronically may exhibit withdrawal symptoms.
Labor and Delivery:
ORAMORPH SR is not recommended for use in women during and immediately prior to labor. Occasionally, opioid analgesics may prolong labor through actions which temporarily reduce the strength, duration and frequency of uterine contractions.
Neonates, whose mothers received opioid analgesics during labor, should be observed closely for signs of respiratory depression. A specific narcotic antagonist, naloxone, should be available for reversal of narcotic-induced respiratory depression in the neonate.
Nursing Mothers:
ORAMORPH SR should not be given to nursing mothers because morphine is excreted in maternal milk. Effects on the nursing infant are not known, but withdrawal symptoms can occur in breast-fed infants when maternal administration of morphine sulfate is stopped.
Pediatric Use:
ORAMORPH SR has not been evaluated in children. Its use in the pediatric population is, therefore, not recommended.
Geriatric Use:
The pharmacodynamic effects of morphine in the aged 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. Individualization of doses must receive careful attention in elderly patients.
Information for Patients:
If clinically advisable, patients receiving ORAMORPH SR brand of morphine sulfate sustained release tablets, should be given the following instructions by the physician:
- Morphine may produce psychological and/or physical dependence. For this reason, the dose of the drug should not be increased without consulting a physician.
- Morphine may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating machinery).
- Morphine should not be taken with alcohol or other CNS depressants (sleep aids, tranquilizers) because additive effects, including CNS depression, may occur. A physician should be consulted if other prescription and/or over-the-counter medications are currently being used or are prescribed for future use.
- For women of childbearing potential, who become or are planning to become pregnant, a physician should be consulted regarding analgesics and other drug use.
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