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Morphine (Morphine Sulfate) - Warnings and Precautions

 
 



WARNINGS

(See also: CLINICAL PHARMACOLOGY)

Impaired Respiration

Respiratory depression is the chief hazard of all morphine preparations. Respiratory depression occurs most 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 with chronic obstructive pulmonary disease or cor pulmonale, and in patients having a substantially decreased respiratory reserve, hypoxia, hypercapnia, or preexisting respiratory depression. In such patients, even usual therapeutic doses of morphine 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 morphine 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. Morphine produces effects which may obscure neurologic signs of further increases in pressure in patients with head injuries.

Hypotensive Effect

Morphine sulfate extended-release tablets, like all opioid analgesics, 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.) Morphine sulfate extended-release tablets may produce orthostatic hypotension in ambulatory patients.

Morphine sulfate extended-release tablets, like all opioid analgesics, should be administered with caution to patients in circulatory shock, since vasodilation produced by the drug may further reduce cardiac output and blood pressure.

Interactions with other CNS Depressants

Morphine sulfate extended-release tablets, like all opioid analgesics, should be used with great caution and in reduced dosage in patients who are concurrently receiving other central nervous system depressants including sedatives or hypnotics, general anesthetics, phenothiazines, other tranquilizers and alcohol because respiratory depression, hypotension and profound sedation or coma may result.

Interactions with Mixed Agonist/Antagonist Opioid Analgesics

From a theoretical perspective, agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, butorphanol and buprenorphine) should NOT be administered to a patient who has received or is receiving a course of therapy with a pure opioid agonist analgesic. In these patients, mixed agonist/antagonist analgesics may reduce the analgesic effect or may precipitate withdrawal symptoms.

Drug Dependence

Morphine can produce drug dependence and has a potential for being abused. Tolerance as well as psychological and physical dependence may develop upon repeated administration. Physical dependence, however, is not of paramount importance in the management of terminally ill patients or any patients in severe pain. Abrupt cessation or a sudden reduction in dose after prolonged use may result in withdrawal symptoms. After prolonged exposure to opioid analgesics, if withdrawal is necessary, it must be undertaken gradually. (See DRUG ABUSE AND DEPENDENCE.)

Infants born to mothers physically dependent on opioid analgesics may also be physically dependent and exhibit respiratory depression and withdrawal symptoms. (See DRUG ABUSE AND DEPENDENCE.)

Other

Although extremely rare, cases of anaphylaxis have been reported.

PRECAUTIONS

(See also: CLINICAL PHARMACOLOGY)

Special Precautions Regarding Morphine Sulfate Extended-Release Tablets, 200 mg.

Morphine sulfate extended-release tablets, 200 mg are for use only in opioid tolerant patients requiring daily morphine equivalent dosages of 400 mg or more. Care should be taken in its prescription and patients should be instructed against use by individuals other than the patient for whom it was prescribed, as this may have severe medical consequences for that individual.

General

Morphine sulfate extended-release tablets are intended for use in patients who require more than several days continuous treatment with a potent opioid analgesic. The extended-release nature of the formulation allows it to be administered on a more convenient schedule than conventional immediate-release oral morphine products. (See CLINICAL PHARMACOLOGY: Pharmacokinetics and Metabolism.) However, morphine sulfate extended-release tablets do not release morphine continuously over the course of a dosing interval. The administration of single doses of morphine sulfate extended-release tablets on a ql2h dosing schedule will result in higher peak and lower trough plasma levels than those that occur when an identical daily dose of morphine is administered using conventional oral formulations on a q4h regimen. The clinical significance of greater fluctuations in morphine plasma level has not been systematically evaluated. (See DOSAGE AND ADMINISTRATION.)

As with any potent opioid, it is critical to adjust the dosing regimen for each patient individually, taking into account the patient’s prior analgesic treatment experience. Although it is clearly impossible to enumerate every consideration that is important to the selection of the initial dose and dosing interval of morphine sulfate extended-release tablets, attention should be given to 1) the daily dose, potency, and characteristics of the opioid the patient has been taking previously (e.g., whether it is pure agonist or mixed agonist/antagonist), 2) the reliability of the relative potency estimate used to calculate the dose of morphine needed [N.B. potency estimates may vary with the route of administration], 3) the degree of opioid tolerance, if any, and 4) the general condition and medical status of the patient.

Selection of patients for treatment with morphine sulfate extended-release tablets should be governed by the same principles that apply to the use of morphine or other potent opioid analgesics. Specifically, the increased risks associated with its use in the following populations should be considered: 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 psychosis; prostatic hypertrophy or urethral stricture; acute alcoholism; delirium tremens; kyphoscoliosis; or inability to swallow.

The administration of morphine, like all opioid analgesics, may obscure the diagnosis or clinical course in patients with acute abdominal conditions.

Morphine may aggravate pre-existing convulsions in patients with convulsive disorders. Morphine should be used with caution in patients about to undergo surgery of the biliary tract since it may cause spasm of the sphincter of Oddi. Similarly, morphine should be used with caution in patients with acute pancreatitis secondary to biliary tract disease.

Information for Patients

If clinically advisable, patients receiving morphine sulfate extended-release tablets should be given the following instructions by the physician:

  1. Appropriate pain management requires changes in the dose to maintain best pain control. Patients should be advised of the need to contact their physician if pain control is inadequate, but not to change the dose of morphine sulfate extended-release tablets without consulting their physician.
  2. Morphine may impair mental and/or physical ability required for the performance of potentially hazardous tasks (e.g., driving, operating machinery). Patients started on morphine sulfate extended-release tablets or whose dose has been changed should refrain from dangerous activity until it is established that they are not adversely affected.
  3. 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 medications are currently being used or are prescribed for future use.
  4. For women of childbearing potential who become or are planning to become pregnant, a physician should be consulted regarding analgesics and other drug use.
  5. Upon completion of therapy, it may be appropriate to taper the morphine dose, rather than abruptly discontinue it.
  6. While psychological dependence ("addiction") to morphine used in the treatment of pain is very rare, morphine is one of a class of drugs known to be abused and should be handled accordingly.
  7. The morphine sulfate extended-release tablet, 200 mg is for use only in opioid-tolerant patients requiring daily morphine equivalent dosages of 400 mg or more. Special care must be taken to avoid accidental ingestion or the use by individuals (including children) other than the patient for whom it was originally prescribed, as such unsupervised use may have severe, even fatal, consequences.

Drug Interactions

(See also: WARNINGS)

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 morphine sulfate extended-release tablets, may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression.

Carcinogenicity / Mutagenicity / 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

Adequate animal studies on reproduction have not been performed to determine whether morphine affects fertility in males or females. 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.

Morphine sulfate extended-release tablets should be used in pregnant women only when clearly needed. (See also: PRECAUTIONS: Labor and Delivery, and DRUG ABUSE AND DEPENDENCE.)

Nonteratogenic effects

Infants born of mothers who have been taking morphine chronically may exhibit withdrawal symptoms.

Labor and Delivery

Morphine sulfate extended-release tablets are 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. However, this effect is not consistent and may be offset by an increased rate of cervical dilatation which tends to shorten labor.

Neonates whose mothers received opioid analgesics during labor should be observed closely for signs of respiratory depression. A specific opioid antagonist, naloxone, should be available for reversal of opioid-induced respiratory depression in the neonate.

Nursing Mothers

Low levels of morphine have been detected in the breast milk. Withdrawal symptoms can occur in breast-feeding infants when maternal administration of morphine sulfate is stopped. Ordinarily, nursing should not be undertaken while a patient is receiving morphine sulfate extended-release tablets since morphine may be excreted in the milk.

Pediatric Use

Use of morphine sulfate extended-release tablets has not been evaluated systematically in pediatric patients.

Geriatric Use

Clinical studies of morphine sulfate extended-release tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. 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.

Page last updated: 2006-04-07

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