Each mL of Roxanol™ contains:

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

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

Morphine Sulfate acts as a narcotic analgesic.

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

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, chronic pain 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.

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

20 mg per mL

NDC 66479-560-03: Bottles of 30 mL with calibrated dropper.

NDC 66479-560-12: Bottles of 120 mL with calibrated dropper.

NDC 66479-560-24: Bottles of 240 mL with calibrated spoon.

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 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. Rev.10-2005. FDA rev date:

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 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 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.

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 anaesthetics, hypnotics, barbiturates, phenothiazines, chloral hydrate, glutethimide, sedatives, MAO inhibitors (including procarbazine hydro-chloride), antihistamines, β-blockers (propranolol), alcohol, furazolidone and other narcotics may enhance the depressant effects of morphine.

Morphine may increase anticoagulant< activity of coumarin and other anticoagulants.

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.

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.

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.

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 narcotic antagonist naloxone 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.

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.

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

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

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 orthos-tatic hypotension in ambulatory patients.

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

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

MORPHINE 20 MG/ML CONCENTRATE - ORAL

(MORE-feen)

COMMON BRAND NAME(S): Roxanol

USES: Morphine is used to treat moderate to severe pain. It acts on certain centers in the brain to give you pain relief. This medication is a narcotic pain reliever (opiate-type).

HOW TO USE: Take this medication by mouth with or without food as directed by your doctor. If you have nausea, it may help to take this drug with food. Consult your doctor or pharmacist about other ways to decrease nausea (such as taking antihistamines, lying down for 1 to 2 hours with as little head movement as possible).

This product is very strong. Measure the dose carefully using the dropper provided with the medication. Be careful not to confuse the dose of morphine in milligrams (mg) with the dose in milliliters (mL). Each milliliter of this product contains 20 milligrams of morphine. Make sure to check and measure the dose carefully before taking it. Ask your doctor or pharmacist if you are not sure how to measure this medication.

The dosage is based on your medical condition and response to treatment. Do not increase your dose, take the medication more frequently, or take it for a longer time than prescribed. Properly stop the medication when so directed.

Pain medications work best if they are used when the first signs of pain occur. If you wait until the pain has worsened, the medication may not work as well.

You may also take long-acting narcotic medications or use narcotic patches for ongoing pain if so directed by your doctor. In that case, this medication might be used for sudden (breakthrough) pain only as needed. Also follow your doctor's or pharmacist's instructions for safely using non-narcotic pain relievers (such as naproxen, ibuprofen). Ask your doctor or pharmacist if you have any questions.

This medication may cause dependence, especially if it has been used regularly for a long time or in high doses. In such cases, withdrawal reactions (such as restlessness, watery eyes, widened pupils, sweating, runny nose) may occur if you suddenly stop this drug. To prevent withdrawal reactions, your doctor may reduce your dose gradually. Consult your doctor or pharmacist for more details, and report any withdrawal reactions immediately.

When this medication is used for a long time, it may not work as well. Your doctor may need to increase your dose or change your medication. Talk with your doctor if this medication stops working well.

Along with its benefits, this medication may rarely cause abnormal drug-seeking behavior (addiction). This risk may be increased if you have abused alcohol or drugs in the past. Take this medication exactly as prescribed to lessen the risk of addiction.

Tell your doctor if your pain persists or worsens.

SIDE EFFECTS: Nausea, vomiting, constipation, lightheadedness, dizziness, drowsiness, increased sweating, or dry mouth may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

To prevent constipation, maintain a diet adequate in fiber, drink plenty of water, and exercise. Consult your pharmacist for help in selecting a laxative (such as a stimulant type with stool softener).

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: slow/shallow breathing, fainting, mental/mood changes (such as agitation, hallucinations, confusion), difficulty urinating, vision changes, slow/fast heartbeat.

Tell your doctor immediately if any of these rare but very serious side effects occur: severe stomach/abdominal pain, change in the amount of urine, seizures.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking morphine, tell your doctor or pharmacist if you are allergic to it; or to other narcotic pain medications (such as codeine); or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: certain bowel diseases (paralytic ileus, infectious diarrhea).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, liver disease, lung diseases (such as asthma, chronic obstructive pulmonary disease-COPD), breathing problems (such as slow/shallow breathing, sleep apnea), a certain spinal problem (kyphoscoliosis), certain heart problems (irregular heartbeat), personal or family history of regular use/abuse of drugs/alcohol, brain disorders (such as seizures, head injury, tumor, increased intracranial pressure), underactive thyroid (hypothyroidism), difficulty urinating (for example, due to enlarged prostate or narrowed urethra), disease of the pancreas (such as pancreatitis), mental/mood disorders (such as toxic psychosis), gallbladder disease, adrenal gland problem (such as Addison's disease), intestinal disorders (such as colitis, blockage).

This drug may make you dizzy or drowsy. Use caution while driving, using machinery, or doing any activity that requires alertness. Avoid alcoholic beverages because they may increase the risk of this drug's side effects.

To lower your risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Before having surgery, tell your doctor or dentist that you are using this medication.

This product may contain sugar. Caution is advised if you have diabetes. Ask your doctor or pharmacist about using this product safely.

Older adults may be more sensitive to the effects of this drug, especially slow/shallow breathing and drowsiness.

During pregnancy, this medication should be used only when clearly needed. Using it for long periods or in high doses near the expected delivery date is not recommended because of possible harm to the unborn baby. Discuss the risks and benefits with your doctor. Infants born to mothers who have used this medication for a long time may have withdrawal symptoms such as irritability, abnormal/persistent crying, vomiting, or diarrhea. Tell your doctor immediately if you notice any of these symptoms in your newborn.

This drug passes into breast milk and the effect on a nursing infant is not known. Discuss the risks and benefits with your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

This drug should not be used with the following medication because a very serious interaction may occur: naltrexone.

If you are currently using this medication listed above, tell your doctor or pharmacist before starting morphine.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: cimetidine, rifampin, certain medications for pain (opiate partial agonists such as butorphanol, nalbuphine, pentazocine).

The risk of serious side effects (such as slow/shallow breathing, severe drowsiness/dizziness) may be increased if this medication is taken with other products that may also affect breathing or cause drowsiness. Therefore, tell your doctor or pharmacist if you are taking other products such as alcohol, anti-seizure drugs (such as phenobarbital), medicine for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants, other narcotic pain relievers (such as codeine), and psychiatric medicines (such as risperidone, amitriptyline, trazodone). Your medications or doses of your medications may need to be changed.

Check the labels on all your medicines (such as cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

This medication may interfere with certain laboratory tests (including amylase and lipase levels), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: slow/shallow breathing, severe drowsiness, slow heartbeat, severe dizziness, pinpoint pupils.

NOTES: Do not share this medication with others. It is against the law.

This medication has been prescribed for your current condition only. Do not use it later for another condition unless told to do so by your doctor. A different medication may be necessary in that case.

MISSED DOSE: If you take this medication regularly and miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.