DESCRIPTION

Each mL of RoxanolTM contains:

Morphine Sulfate...................................20 mg

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:

Morphine Sulfate acts as a narcotic analgesic.

CLINICAL PHARMACOLOGY

The major effects of morphine are on the central nervous system and the bowel.  Opioids act as agonists, interacting with sterospecific and saturable bind sites or receptors in the brain and other tissues.

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

INDICATIONS AND USAGE

Morphine is indicated for the relief of severe acute and severe chronic 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; delirium 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 narcoticantagonist.

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.

PRECAUTIONS

General

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 a substantially decreased respiratory re-serve, 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.

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 hy-pertrophy, or urethral stricture

Acute Abdominal Conditions

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

Information for Patients

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 product 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 acififying agents.  Analgesic effect of morphine is potentiated by chlorpromazine and methocarbamol.  CNS depressants such as anaesthetics, hypnotics, barbiiturates, phenothiazines, chloral hydrate, glutethimide, sedatives, MAO inhibitors (including procarbazine hydrochloride), antihistamines, B-blockers (propranolol), alcohol, furazolidone and other narcotics may enhance the depressant effects of morphine.

Morphine may increase anticoagulant activity of courmarin and other anticoagulants.

Carcinogenicity/Mutagenicity

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

Pregnancy

Teratogenic Effects:  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 OF OTHER NARCOTIC ANALGESICS, ARE RESPIRA-TORY 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 suffering severe pain. In such individuals, lower doses are available. Some adverse reactions may be alleviated in the ambulatory patient if he 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.

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

Treatment of the most frequent adverse reactionsConstipation

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 fecal impaction is a possible cause to consider before antidiarrheal measures are employed.

Nausea and Vomiting

Phenothiazines and antihistamines can be effective treatments of 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, a narcotic, is a Schedule II controlled substance under the Federal Controlled Substance Act. 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.

OVERDOSAGE

Signs and Symptoms

Serious overdose with morphine 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, skeletal muscle flaccidity, cold or clammy skin, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur.

Treatment

In all cases of suspected overdosage, call 800-222-1222 to obtain the most up-to-date information about the treatment of overdose. By calling this number, you will be automatically connected to your local Poison Control Center.

Primary attention should be given to the re-establishment of adequate respiratory exchange through provision of a patent airway and the institution of assisted or controlled ventilation. The narcoticantagonistnaloxone is a specific antidote against respiratory depression which may result from overdosage or unusual sensitivity to narcotics, including morphine. Therefore, an appropriate dose of naloxone (usual initial adult dose: 0.4 mg) should be administered, prefer-ably by the intravenous route and simultaneously with efforts at respiratory resuscitation. Since the duration of action of morphine may exceed that of the antagonist, the patient should be kept under continued surveillance and repeated doses of the antagonist should be administered as needed to maintain adequate respiration.

An antagonist should not be administered in the absence of clinically significant respiratory or cardio-vascular depression.

Oxygen, intravenous fluids, vasopressors and other supportive measures should be employed as indicated.

Gastric emptying may be useful in removing unabsorbed drug.

DOSAGE AND ADMINISTRATION

CAUTION: Roxanol™ (Morphine Sulfate 20 mg/mL) is a HIGHLY CONCENTRATED solution of Morphine Sulfate for Oral Administration.Error in dosage or confusion between milligrams (mg) of morphine and milliliters (mL) of solution may cause significant over-dosage. Dosing instructions should be clearly pre-scribed in milligrams (mg) of morphine and milliliters (mL) of solution. VERIFY CORRECT DOSE AND VOLUME BEFORE ADMINISTRATION TO PATIENT.

Usual Adult Oral Dose

10 to 30 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.

For control of severe, chronicpain in patients with certain terminal diseases, this drug should be administered on a regularly scheduled basis, every 4 hours, at the lowest dosage level that will 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 in a pain exhausted patient. The dose, therefore, should be maintained for at least three days before reduction, if respiratory activity and other vitals 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

Roxanol™
Morphine Sulfate (Immediate Release)
Oral Solution (Concentrate)

20 mg per mL

NDC 54868-3416-0: Bottles of 30 mL with calibrated dropper.

Store at 25°C (77°F);excursions are permitted to 15°-30°C (59°-86°F) [See USP Controlled Room Temperature]

DEA Order Form Required.

ROXANOL (morphine sulfate) is a trademark of Xanodyne Pharmaceuticals, Inc.

© 2005 Xanodyne Pharmaceuticals, Inc.,

Manufactured by:
Boehringer Ingelheim Roxane, Inc.
Columbus, OH 43216

Marketed by:
Xanodyne Pharmaceuticals, Inc.
Newport, KY 41071.

10002854/01

Rev. 10-2005

PRINCIPAL DISPLAY PANEL

Roxanol™
Morphine Sulfate (Immediate Release)
Oral Solution (Concentrate)

20 mg per mL