(See also: CLINICAL PHARMACOLOGY)

MS CONTIN (MORPHINE SULFATE CONTROLLED-RELEASE) TABLETS ARE TO BE SWALLOWED WHOLE AND ARE NOT TO BE BROKEN, CHEWED, DISSOLVED, OR CRUSHED. TAKING BROKEN, CHEWED, DISSOLVED, OR CRUSHED MS CONTIN® TABLETS LEADS TO RAPID RELEASE AND ABSORPTION OF A POTENTIALLY FATAL DOSE OF MORPHINE.

MS CONTIN100 AND 200 mg Tablets ARE FOR USE IN OPIOID-TOLERANT PATIENTS ONLY. These tablet strengths may cause fatal respiratory depression when administered to patients not previously exposed to opioids.

MS CONTIN 100 AND 200 mg Tablets are for use only in opioid-tolerant patients requiring daily morphine equivalent dosages of 200 mg or more for the 100 mg tablet and 400 mg or more for the 200 mg tablet. Care should be taken in the prescribing of these tablet strengths. Patients should be instructed against use by individuals other than the patient for whom it was prescribed, as such inappropriate use may have severe medical consequences, including death.

Misuse, Abuse and Diversion of Opioids

Morphine is an opioid agonist and a Schedule II controlled substance. Such drugs are sought by drug abusers and people with addiction disorders and are subject to criminal diversion.

Morphine can be abused in a manner similar to other opioid agonists, legal or illicit. This should be considered when prescribing or dispensing MS CONTIN® in situations where the physician or pharmacist is concerned about an increased risk of misuse, abuse, or diversion.

MS CONTIN can be abused by crushing, chewing, snorting or injecting the dissolved product. These practices will result in the uncontrolled delivery of the opioid and pose a significant risk to the abuser that could result in overdose and death (see WARNINGS: Drug Abuse and Addiction).

Concerns about abuse, addiction, and diversion should not prevent the proper management of pain.

Healthcare professionals should contact their State Professional Licensing Board, or State Controlled Substances Authority for information on how to prevent and detect abuse or diversion of this product.

Interactions with Alcohol and Drugs of Abuse

Morphine may be expected to have additive effects when used in conjunction with alcohol, other opioids, or illicit drugs that cause central nervous system depression because respiratory depression, hypotension, and profound sedation or coma may result. (See WARNINGS: Interactions with other CNS Depressants.)

Drug Abuse and Addiction

MS CONTIN is a mu-agonist opioid with an abuse liability similar to other opioid agonists and is a Schedule II controlled substance. MS CONTIN and other opioids used in analgesia, can be abused and are subject to criminal diversion.

Drug addiction is characterized by compulsive use, use for non-medical purposes, and continued use despite harm or risk of harm. Drug addiction is a treatable disease, utilizing a multi-disciplinary approach, but relapse is common.

“Drug-seeking” behavior is very common in addicts and drug abusers. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing or referral, repeated “loss” of prescriptions, tampering with prescriptions and reluctance to provide prior medical records or contact information for other treating physician(s). “Doctor shopping” to obtain additional prescriptions is common among drug abusers and people suffering from untreated addiction.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Physicians should be aware that addiction may not be accompanied by concurrent tolerance and symptoms of physical dependence in all addicts. In addition, abuse of opioids can occur in the absence of true addiction and is characterized by misuse for non-medical purposes, often in combination with other psychoactive substances. MS CONTIN®, like other opioids, has been diverted for non-medical use. Careful record keeping of prescribing information, including quantity, frequency, and renewal requests is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic re-evaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

MS CONTIN is intended for oral use only as an intact tablet. Abuse of the crushed tablet poses a hazard of overdose and death. This risk is increased with concurrent abuse of alcohol and other substances. Due to the presence of talc as one of the excipients in tablets, parenteral abuse can be expected to result in local tissue necrosis, infection, pulmonary granulomas, and increased risk of endocarditis and valvular heart injury. Parenteral drug abuse is commonly associated with transmission of infectious diseases such as hepatitis and HIV.

Respiratory Depression

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 pre-existing 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 pre-existing increase in intracranial pressure. Morphine produces effects which may obscure neurologic signs of further increases in pressure in patients with head injuries.

Hypotensive Effect

MS CONTIN®, 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. MS CONTIN may produce orthostatic hypotension in ambulatory patients.

MS CONTIN, 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

MS CONTIN, 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.

Other

Although extremely rare, cases of anaphylaxis have been reported.

(See also: CLINICAL PHARMACOLOGY)

Special precautions regarding MS CONTIN 100 mg and 200 mg Tablets

MS CONTIN 100 mg and 200 mg Tablets are for use only in opioid-tolerant patients requiring daily morphine equivalent dosages of 200 or more for the 100 mg tablet and 400 mg or more for the 200 mg tablet. 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

MS CONTIN Tablets are a controlled-release oral formulation of morphine sulfate indicated for the management of moderate to severe pain when a continuous, around-the-clock analgesic is needed for an extended period of time. MS CONTIN does not release morphine continuously over the course of a dosing interval. The administration of single doses of MS CONTIN on a q12h 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.)

Selection of patients for treatment with MS CONTIN® 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 convulsions in patients with convulsive disorders, and all opioids may induce or aggravate seizures in some clinical settings.

Interactions with Mixed Agonist/Antagonist Opioid Analgesics

Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, and butorphanol) should be administered with caution to a patient who has received or is receiving a course of therapy with a pure opioid agonist analgesic such as morphine sulfate. In this situation, mixed agonist/antagonist analgesics may reduce the analgesic effect of morphine sulfate and/or may precipitate withdrawal symptoms in these patients.

Use in Pancreatic/Biliary Tract Disease

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.

Tolerance

Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug's effects over time. Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

Physical Dependence

Physical dependence is a state of adaptation that is manifested by an opioid specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist.

The opioid abstinence or withdrawal syndrome is characterized by some or all of the following: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, piloerection, myalgia, mydriasis, irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.

In general, opioids should not be abruptly discontinued (see DOSAGE AND ADMINISTRATION: Cessation of Therapy).

Use in Drug and Alcohol Addiction

MS CONTIN is an opioid with no approved use in the management of addiction disorders. Its proper usage in individuals with drug or alcohol dependence, either active or in remission, is for the management of pain requiring opioid analgesia.

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.

MS CONTIN® should be used in pregnant women only if the need for strong opioid analgesia clearly outweighs the potential risk to the fetus. (See also: PRECAUTIONS: Labor and Delivery, and WARNINGS: DRUG ABUSE AND ADDICTION.)

Labor and Delivery

MS CONTIN 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. 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 narcotic antagonist, naloxone, should be available for reversal of narcotic-induced respiratory depression in the neonate.

Neonatal Withdrawal Syndrome

Chronic maternal use of opioids during pregnancy can affect the fetus with subsequent withdrawal symptoms. Neonatal withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, abnormal crying, tremor, vomiting, diarrhea and subsequent weight loss or failure to gain weight, and may result in death. The onset, duration and severity of neonatal withdrawal syndrome varies based on the drug used, duration of use, the dose of last maternal use, and rate of elimination by the newborn. Use standard care as medically appropriate.

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 MS CONTIN since morphine may be excreted in the milk.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

MS CONTIN Tablets are not to be chewed, crushed, dissolved or divided for administration.

Geriatric Use

Clinical studies of MS CONTIN 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.

Bookmark this page: