FDA Label for Morphine Sulfate

Other

(WARNING: MAY BE HABIT FORMING)

A Schedule CII Narcotic

DEA Order Form Required

Caution: Federal law prohibits transfer of this drug to any person other than the patient for whom it was prescribed.

Manufactured by

Perrigo®
Minneapolis, MN 55427
2124053

(05-12)

Description

Each suppository for rectal administration contains 5 mg, 10 mg, 20 mg, or 30 mg of Morphine Sulfate in a bland, specially formulated Hydrogenated Vegetable Oil Base with BHA and BHT as preservatives, as well as other ingredients.

Chemically, Morphine Sulfate is, Morphinan-3, 6-diol, 7,8-didehydro-4,5-epoxy-17-methyl-, (5a,6a)-, sulfate (2:1) (salt), pentahydrate, which can be represented by the following structural formula:

Clinical Pharmacology

Morphine is a potent narcotic analgesic; it's principal therapeutic effect is relief of pain. In addition to analgesia, narcotics produce drowsiness, changes in mood, and mental clouding; although neither sensory modalities nor motor activity are blocked at therapeutic doses. There is no intrinsic limit to the analgesic effect. Clinically, however, dosage limitations are imposed by the adverse effects, primarily respiratory depression, nausea, and vomiting, which can result from high doses.

Morphine has diverse additional actions. It depresses the respiratory center, stimulates the vomiting center, depresses the cough reflex, constricts the pupils, increases the tone of gastrointestinal and genitourinary tracts, and produces mild vasodilation. Morphine is detoxified in the liver by means of conjugation with glucuronic acid. Small amounts of the free drug and larger amounts of conjugated morphine are present in the urine, and these account for most of the administered drug. Ninety percent of the total excretion occurs within the first 24 hours.

Morphine is about two-thirds absorbed from the gastrointestinal tract with the maximum analgesic effect occuring 20-60 minutes post administration.

Indications And Usage

Morphine is indicated for the relief of severe chronic pain, and severe acute pain.

Contraindications

Hypersensitivity to morphine; respiratory insufficiency or depression; severe CNS depression; attack of bronchial asthma; heart failure secondary to chronic lung disease; cardiac arrhythmias; increased intracranial or cerebrospinal pressure; head injuries; brain tumor; acute alcoholism, delerium tremens; convulsive disorders; after biliary tract surgery; suspected surgical abdomen; surgical anastomosis; concomitantly with MAO inhibitors or within 14 days of such treatment.

Warnings

Morphine can cause tolerance, psychological and physical dependence. Withdrawal will occur on abrupt discontinuation or administration of a narcotic antagonist.

Interaction With Other Central-Nervous-System Depressants

Morphine should be used with caution and in reduced dosage in patients who are concurrently receiving other narcotic analgesics, general anesthetics, phenothiazines, other tranquilizers, sedative-hypnotics, tricyclic antidepressants, and other CNS depressants (including alcohol). Respiratory depression, hypotension, and profound sedation or coma may result.

Head Injury And Increased Intracranial Pressure

The respiratory depressant effects of morphine and its capacity to elevate cerebrospinal-fluid pressure may be markedly exaggerated in the presence of increased intracranial pressure. Furthermore, narcotics produce side effects that may obscure the clinical course of patients with head injuries. In such patients, morphine must be used with caution and only if it is deemed essential.

Asthma And Other Respiratory Conditions

Morphine should be used with caution in patients having an acute asthmatic attack, in those with chronic obstructive pulmonary disease or cor pulmonale, and in individuals with substantially decreased respiratory reserve, preexisting 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.

Hypotensive Effect

the administration of morphine may result in severe hypotension in an individual whose ability to maintain his blood pressure has already been compromised by a depleted blood volume or concurrent administration of such drugs as the phenothiazines or certain anesthetics.

Supraventricular Tachycardias

Caution should be used in patients with atrial flutter and other supraventricular tachycardias due to a possible vagolytic action which may produce a significant increase in the ventricular response rate.

Special Risk Patients

Morphine should be given with caution and the initial dose should be reduced in certain patients, such as the elderly or debilitated and those with severe impairment of hepatic or renal function, hypothyroidism, Addison's disease, prostatic hypertrophy, or urethral stricture.

Convulsions

Morphine may aggravate preexisting convulsive disorders. Convulsions may occur in individuals without a history of convulsive disorders if dosage is substantially escalated above recommended levels because of tolerance development.

Acute Abdominal Conditions

The administration of morphine or other narcotics may obscure the diagnosis or clinical course in patients with acute abdominal conditions.

Use In Ambulatory Patients

Morphine may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car or operating machinery. The patient should be cautioned accordingly.

Morphine, like other narcotics, may produce orthostatic hypotension in ambulatory patients.

Patients should be cautioned about the combined effects of alcohol or other central nervous system depressants with morphine.

Drug Interactions

Generally, effects of morphine may be potentiated by alkalizing agents and antagonized by acidifying agents. Analgesic effect of morphine is potentiated by chlorpromazine and methocarbamol, CNS depressants such as anesthetics, hypnotics, barbiturates, phenothiazines, chloral hydrate, glutethimide, sedatives, MAO inhibitors (including procarbazine hydrochloride), antihistamines, beta-blockers (propranolol), alcohol, furazolidone and other narcotics may enhance the depressant effects of morphine.

Morphine may increase anticoagulant activity of Coumadin^® and other anticoagulants.

Carcinogenicity/Mutagenicity

Long-term studies to determine the carcinogenic and mutagenic potential of morphine are not available.

Pregnancy Category C:

Animal reproduction studies have not been conducted with morphine. It is also not known whether morphine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Morphine should be given to a pregnant woman only if clearly needed.

Labor And Delivery

Morphine readily crosses the placental barrier and if administered during labor may lead to respiratory depression in the neonate.

Nursing Mothers

Morphine has been detected in human milk. For this reason, caution should be exercised when morphine is administered to a nursing woman.

Pediatric Usage

Safety and effectiveness in children have not been established.

Adverse Reactions

THE MAJOR HAZARDS OF MORPHINE, AS WITH OTHER NARCOTIC ANALGESICS, ARE RESPIRATORY DEPRESSION AND, TO A LESSER DEGREE, CIRCULATORY DEPRESSION, RESPIRATORY ARREST, SHOCK, AND CARDIAC ARREST HAVE OCCURRED.

The most frequently observed adverse reactions include lightheadedness, dizziness, sedation, nausea, vomiting and sweating. These effects seem to be more prominent in ambulatory patients and in those who are not suffering severe pain. In such individuals, lower doses are advisable. Some adverse reactions may be alleviated in the ambulatory patient who lies down.

Other adverse reactions include the following:

Central Nervous System - Euphoria, dysphoria, weakness, headache, insomnia, agitation, disorientation, and visual disturbances.

Gastrointestinal - Dry mouth, anorexia, constipation, and biliary tract spasm.

Cardiovascular - Flushing of the face, bradycardia, palpitation, faintness and syncope.

Genitourinary - Urinary retention or hesitancy, anti-diuretic effect, and reduced libido and/or potency.

Allergic - Pruritus, urticaria, other skin rashes, edema, and rarely hemorrhagic urticaria.

Treatment of the most frequent adverse reactions:

Constipation - Ample intake of water or other liquids should be encouraged. Concomitant administration of a stool softener and a peristaltic stimulant with the narcotic analgesic can be an effective preventive measure for those patients in need of therapeutics. If elimination does not occur for two days, an enema should be administered to prevent impaction.

In the event diarrhea occurs, seepage around a fecal impaction is a possible cause to consider before antidiarrheal measures are employed.

Nausea and Vomiting - Phenothiazines and antihistamines can be effective treatments for nausea of the medullary and vestibular sources respectively. However, these drugs may potentiate the side effects of the narcotic or the antinauseant.

Drowsiness (sedation) - Once pain control is achieved, undesirable sedation can be minimized by titrating the dosage to a level that just maintains a tolerable pain or pain free state.

Drug Abuse And Dependence

Morphine Sulfate is a Schedule II controlled substance. As with other narcotics, some patients may develop a physical and psychological dependence on morphine. They may increase dosage without consulting a physician and subsequently may develop a physical dependence on the drug. In such cases, abrupt discontinuance may precipitate typical withdrawal symptoms, including convulsions. Therefore, the drug should be withdrawn gradually from any patient known to be taking excessive dosages over a long period of time.

In treating the terminally ill patient the benefit of pain relief may outweigh the possibility of drug dependence. The chance of drug dependence is substantially reduced when the patient is placed on scheduled narcotic programs instead of a "pain to relief of pain" cycle typical of a PRN regimen.

Signs And Symptoms:

Serious overdosage is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, Cheyne-Stokes respiration, cyanosis), extreme somnolence progressing to stupor or coma, maximally constricted pupils, skeletal muscle flaccidity, cold and clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, particularly by the IV route, apnea, circulatory collapse, cardiac arrest, and death may occur.

Treatment Of Overdose:

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. If depressed respiration is associated with muscular rigidity, an IV neuromuscular blocking agent may be required to facilitate assisted or controlled respiration.

The narcotic antagonists-nalorphine, naloxone, and levallorphan are specific antidotes against respiratory depression resulting from overdosage or unusual sensitivity to narcotics. Thus, an antagonist should be administered, preferably by the IV route, simultaneously with efforts at respiratory resuscitation. Since the duration of action of morphine may exceed that of the antagonist, repeated doses of the antagonist may be required to maintain adequate respiration; the patient must be kept under surveillance.

Oxygen, intravenous fluids, vasopressors, and other supportive measures should be employed as indicated. In cases of oral overdose, the stomach should be evacuated by emesis or gastric lavage if treatment can be instituted within 2 hours following ingestion. The patient should be observed closely for a rise in temperature or pulmonary complications that may signal the need for institution of antibiotic therapy.

Dosage And Administration For Morphine Sulfate Suppositories

Usual Adult Dose: 10 to 20 mg every 4 hours or as directed by physician.

Dosage is a patient dependent variable, therefore increased dosage may be required to achieve adequate analgesia.

Note: Medication may suppress respiration in the elderly, the very ill, and those patients with respiratory problems, therefore lower doses may be required.

Morphine Dosage Reduction

During the first two to three days of effective pain relief, the patient may sleep for many hours. This can be misinterpreted as the effect of excessive analgesic dosing rather than the first sign of relief of a pain exhausted patient. The dose, therefore, should be maintained for at least three days before reduction, if respiratory activity and other vital signs are adequate.

Following successful relief of severe pain, periodic attempts to reduce the narcotic dose should be made. Smaller doses or complete discontinuation of the narcotic analgesic may become feasible due to a physiologic change or the improved mental state of the patient.

How Supplied

Morphine Sulfate Suppositories are available in cartons of 12. Easy-to-open, color-coded:

5 mg Suppositories (Red)
12's NDC 0574-7110-12

10 mg Suppositories (Light Blue)
12's NDC 0574-7112-12

20 mg Suppositories (Light Green)
12's NDC 0574-7114-12

30 mg Suppositories (Purple)
12's NDC 0574-7116-12

Principal Display Panel - 5 Mg Suppository Carton

Rx Only

NDC 0574-7110-12

Morphine Sulfate
Suppositories 5 mg
CII

FOR RECTAL USE ONLY
Warning: May be habit forming.

12 Suppositories
UNIT DOSE

Perrigo^®

Principal Display Panel - 10 Mg Suppository Carton

Rx Only

NDC 0574-7112-12

Morphine Sulfate
Suppositories 10 mg
CII

FOR RECTAL USE ONLY
Warning: May be habit forming.

12 Suppositories
UNIT DOSE

Perrigo^®

Principal Display Panel - 20 Mg Suppository Carton

Rx Only

NDC 0574-7114-12

Morphine Sulfate
Suppositories 20 mg
CII

FOR RECTAL USE ONLY
Warning: May be habit forming.

12 Suppositories
UNIT DOSE

Perrigo^®

Principal Display Panel - 30 Mg Suppository Carton

Rx Only

NDC 0574-7116-12

Morphine Sulfate
Suppositories 30 mg
CII

FOR RECTAL USE ONLY
Warning: May be habit forming.

12 Suppositories
UNIT DOSE

Perrigo^®