MS Contin

MS CONTIN is indicated for the management of pain severe enough to require daily, around-theclock, long-term opioid treatment and for which alternative treatment options are inadequate.

Limitations of Use

• Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with extended-release opioid formulations, reserve MS CONTIN for use in patients for whom alternative treatment options (e.g., non-opioid analgesics or immediate-release opioids) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
• MS CONTIN is not indicated as an as-needed (prn) analgesic.

• Purdue Pharma LP

Addiction, Abuse, and Misuse 
MS Contin exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing MS Contin, and monitor all patients regularly for the development of these behaviors or conditions.

Life-Threatening Respiratory Depression 
Serious, life-threatening, or fatal respiratory depression may occur with use of MS Contin. Monitor for respiratory depression, especially during initiation of MS Contin or following a dose increase. Instruct patients to swallow MS Contin tablets whole; crushing, chewing, or dissolving MS Contin tablets can cause rapid release and absorption of a potentially fatal dose of MS Contin.

Accidental Ingestion 
Accidental ingestion of even one dose of MS Contin, especially by children, can result in a fatal overdose of MS Contin.

Neonatal Opioid Withdrawal Syndrome 
Prolonged use of MS Contin during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.

This section provides information on the proper use of a number of products that contain morphine. It may not be specific to MS Contin. Please read with care.

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. This is especially important for elderly patients, who may be more sensitive to the effects of pain medicines. If too much of this medicine is taken for a long time, it may become habit-forming (causing mental or physical dependence).

This medicine comes with a Medication Guide and patient instructions. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Avinza® is taken every 24 hours. Kadian® is taken every 12 or 24 hours at the same time each day. Morphabond™ is taken every 12 hours. Arymo™ ER is taken every 8 or 12 hours.

You may take this medicine with or without food.

Morphine extended-release capsules and tablets should only be used by patients who have already been taking narcotic pain medicines, also called opioids. These patients are called opioid-tolerant. If you are uncertain whether or not you are opioid-tolerant, check with your doctor before using this medicine.

Swallow the extended-release capsules and tablets whole. Do not crush, break, dissolve, or chew them. Do not use extended-release tablets that are broken.

If you cannot swallow the extended-release capsule, you may open it and pour the medicine into a small amount of applesauce. Stir this mixture well and swallow it right away without chewing. Do not receive this medicine through a nasogastric tube.

While taking the extended-release tablet, part of the tablet may pass into your stool. This is normal and nothing to worry about.

Morphine extended-release capsules or tablets work differently from the regular morphine oral solution or tablets, even at the same dose. Do not switch from one brand or form to the other unless your doctor tells you to.

Measure the oral liquid with a marked measuring spoon, oral syringe, or medicine cup. The average household teaspoon may not hold the right amount of liquid.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (extended-release capsules):
  • For moderate to severe pain:
    • Adults—
      • The total amount of milligrams (mg) per day is determined by your doctor. Your doctor may adjust your dose if needed.
      • Avinza®: The capsule is given every 24 hours.
      • Kadian®: The capsule is given every 12 or 24 hours.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage form (extended-release tablets):
  • For moderate to severe pain:
    • Adults—
      • The total amount of milligrams (mg) per day is determined by your doctor. Your doctor may adjust your dose if needed.
      • Arymo™ ER: The tablet is given every 8 or 12 hours.
      • Morphine sulfate: The tablet is given every 8 or 12 hours.
      • Morphabond™: The tablet is given every 12 hours.
      • MS Contin®: The tablet is given every 8 or 12 hours.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage form (solution):
  • For moderate to severe pain:
    • Adults—10 to 20 milligrams (mg) every 4 hours as needed. Your doctor may adjust your dose if needed.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage form (tablets):
  • For moderate to severe pain:
    • Adults—15 to 30 milligrams (mg) every 4 hours as needed. Your doctor may adjust your dose if needed.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss a dose of Arymo™ ER, Avinza®, Kadian®, Morphabond™, or MS Contin®, skip the missed dose and take your next dose at your usual time the next day. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Morphine can cause serious unwanted effects if taken by adults, children, or pets who are not used to strong narcotic pain medicines. Make sure you store the medicine in a safe and secure place to prevent others from getting it.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Abdominal or stomach pain
• blurred vision
• bulging soft spot on the head of an infant
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• change in the ability to see colors, especially blue or yellow
• chest pain or discomfort
• confusion
• cough
• decreased urination
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fainting
• fast, pounding, or irregular heartbeat or pulse
• headache
• hives, itching, or skin rash
• increased sweating
• loss of appetite
• nausea or vomiting
• nervousness
• pounding in the ears
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• severe constipation
• severe vomiting
• shakiness in the legs, arms, hands, or feet
• slow heartbeat
• sweating or chills

• Black, tarry stools
• cold, clammy skin
• feeling of warmth or heat
• flushing or redness of the skin, especially on the face and neck
• irregular, fast or slow, or shallow breathing
• lightheadedness
• loss of consciousness
• low blood pressure or pulse
• painful urination
• pale or blue lips, fingernails, or skin
• pale skin
• pinpoint red spots on the skin
• pounding in the ears
• shakiness and unsteady walk
• unsteadiness, trembling, or other problems with muscle control or coordination
• unusual bleeding or bruising
• very slow heartbeat

Get emergency help immediately if any of the following symptoms of overdose occur:

• Constricted, pinpoint, or small pupils (black part of the eye)
• decreased awareness or responsiveness
• extreme drowsiness
• fever
• increased blood pressure
• increased thirst
• lower back or side pain
• muscle cramps or spasms
• muscle pain or stiffness
• no muscle tone or movement
• severe sleepiness
• swelling of the face, fingers, or lower legs
• weight gain

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Cramps
• difficulty having a bowel movement (stool)
• drowsiness
• false or unusual sense of well-being
• relaxed and calm feeling
• sleepiness or unusual drowsiness
• weight loss

• Absent, missed, or irregular menstrual periods
• agitation
• bad, unusual, or unpleasant (after) taste
• change in vision
• depression
• dry mouth
• face is warm or hot to touch
• floating feeling
• halos around lights
• heartburn or indigestion
• loss in sexual ability, desire, drive, or performance
• muscle stiffness or tightness
• night blindness
• overbright appearance of lights
• problems with muscle control
• redness of the skin
• skin rash
• stomach discomfort or upset
• trouble sleeping
• uncontrolled eye movements

• Abnormal dreams
• change in walking and balance
• change or problem with discharge of semen
• clumsiness or unsteadiness
• confusion as to time, place, or person
• delusions
• dementia
• feeling of constant movement of self or surroundings
• general feeling of discomfort or illness
• holding false beliefs that cannot be changed by fact
• problems with memory
• seeing, hearing, or feeling things that are not there
• sensation of spinning
• unusual excitement, nervousness, or restlessness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

• MS Contin® (morphine sulfate extended-release tablets) 15 mg
  Round, blue-colored, film-coated tablets bearing the symbol PF on one side and M 15 on the other
• MS Contin® (morphine sulfate extended-release tablets) 30 mg
  Round, lavender-colored, film-coated tablets bearing the symbol PF on one side and M 30 on the other
• MS Contin® (morphine sulfate extended-release tablets) 60 mg
  Round, orange-colored, film-coated tablets bearing the symbol PF on one side and M 60 on the other
• MS Contin® (morphine sulfate extended-release tablets) 100 mg
  Round, gray-colored, film-coated tablets bearing the symbol PF on one side and 100 on the other
• MS Contin® (morphine sulfate extended-release tablets) 200 mg
  Capsule-shaped, green-colored, film-coated tablets bearing the symbol PF on one side and M 200 on the other

Controlled Substance

MS Contin contains morphine, a Schedule II controlled substance.

Abuse

MS Contin contains morphine, a substance with a high potential for abuse similar to other opioids including fentanyl, hydrocodone, hydromorphone, methadone, oxycodone, oxymorphone, and tapentadol. MS Contin can be abused and is subject to misuse, addiction, and criminal diversion [see Warnings and Precautions (5.1)].

The high drug content in extended-release formulations adds to the risk of adverse outcomes from abuse and misuse.

All patients treated with opioids require careful monitoring for signs of abuse and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use.

Prescription drug abuse is the intentional non-therapeutic use of an over-the-counter or prescription drug, even once, for its rewarding psychological or physiological effects. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that develop after repeated substance use and includes: a strong desire to take the drug, difficulties in controlling its use, persisting in its use despite harmful consequences, a higher priority given to drug use than to other activities and obligations, increased tolerance, and sometimes a physical withdrawal.

"Drug-seeking" behavior is very common in persons with substance use disorders. 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 healthcare provider(s). "Doctor shopping" (visiting multiple prescribers to obtain additional prescriptions) is common among drug abusers and people suffering from untreated addiction. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with poor pain control.

Abuse and addiction are separate and distinct from physical dependence and tolerance. Healthcare providers 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.

MS Contin, like other opioids, can be diverted for non-medical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, 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.

Risks Specific to Abuse of MS Contin

MS Contin is for oral use only. Abuse of MS Contin poses a risk of overdose and death. This risk is increased with concurrent abuse of MS Contin with alcohol and other central nervous system depressants. Taking cut, broken, chewed, crushed, or dissolved MS Contin enhances drug release and increases the risk of overdose and death.

Due to the presence of talc as one of the excipients in MS Contin, parenteral abuse can be expected to result in local tissue necrosis, infection, pulmonary granulomas, embolism and death, 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.

Dependence

Both tolerance and physical dependence can develop during chronic opioid therapy. Tolerance is the need for increasing doses of opioids to maintain a defined effect such as analgesia (in the absence of disease progression or other external factors). Tolerance may occur to both the desired and undesired effects of drugs, and may develop at different rates for different effects.

Physical dependence results in withdrawal symptoms after abrupt discontinuation or a significant dosage reduction of a drug. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity, (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued opioid usage.

MS Contin should not be abruptly discontinued [see Dosage and Administration (2.5)]. If MS Contin is abruptly discontinued in a physically-dependent patient, withdrawal syndrome may occur. Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis. Other signs and symptoms also may develop, including: irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see Use in Specific Populations (8.1)].

MS Contin (morphine sulfate extended-release tablets) is for oral use and contains morphine sulfate, an opioid agonist.

Each tablet contains the following inactive ingredients common to all strengths: cetostearyl alcohol, hydroxyethyl cellulose, hypromellose, magnesium stearate, polyethylene glycol, talc and titanium dioxide.

The tablet strengths describe the amount of morphine per tablet as the pentahydrated sulfate salt (morphine sulfate).

The 15 mg tablets also contain: FD&C Blue No. 2, lactose, polysorbate 80

The 30 mg tablets also contain: D&C Red No. 7, FD&C Blue No. 1, lactose, polysorbate 80

The 60 mg tablets also contain: D&C Red No. 30, D&C Yellow No. 10, hydroxypropyl cellulose, lactose

The 100 mg tablets also contain: black iron oxide

The 200 mg tablets also contain: D&C Yellow No. 10, FD&C Blue No. 1, hydroxypropyl cellulose

Morphine sulfate is an odorless, white, crystalline powder with a bitter taste. It has a solubility of 1 in 21 parts of water and 1 in 1000 parts of alcohol, but is practically insoluble in chloroform or ether. The octanol: water partition coefficient of morphine is 1.42 at physiologic pH and the pKb is 7.9 for the tertiary nitrogen (mostly ionized at pH 7.4). Its molecular weight is 758.83 and its structural formula is:

Attention Dispenser: Accompanying
Medication Guide must be provided to
the patient upon dispensing.

NDC 42858-631-01

MS Contin®
(morphine sulfate
extended-release tablets)

CII

30 mg

Rhodes

Rx Only

100 Tablets

Attention Dispenser: Accompanying
Medication Guide must be provided to
the patient upon dispensing.

NDC 42858-900-01

MS Contin®
(morphine sulfate
extended-release tablets)

CII

200 mg

Rhodes

Rx Only
100 Tablets

for use in opioid-
tolerant patients
only

MS Contin (morphine) is an opioid pain medication. An opioid is sometimes called a narcotic.

MS Contin extended-release tablets are a strong prescription pain medicine used to treat moderate to severe pain that requires around-the-clock, long-term treatment. MS Contin is used when other pain treatments such as non-opioid pain medicines or immediate-release opioid medicines do not treat the pain well enough or cannot be tolerated.

MS Contin extended-release tablets are for around-the-clock treatment of pain. This form of morphine is not for use on an as-needed basis for pain.

Narcotic (opioid) medication can interact with many other drugs and cause dangerous side effects or death. Be sure your doctor knows if you also use:

• other narcotic medications - opioid pain medicine or prescription cough medicine;

• drugs that make you sleepy or slow your breathing - a sleeping pill, muscle relaxer, sedative, tranquilizer, or antipsychotic medicine; or

• drugs that affect serotonin levels in your body - medicine for depression, Parkinson's disease, migraine headaches, serious infections, or prevention of nausea and vomiting.

This list is not complete. Other drugs may interact with morphine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.