MS Contin

2 DOSAGE AND ADMINISTRATION MS CONTIN should be prescribed only by healthcare providers who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. ( 2.1 ) MS CONTIN 100 mg and 200 mg tablets, a single dose greater than 60 mg, or a total daily dose greater than 120 mg, are only for use in patients in whom tolerance to an opioid of comparable potency has been established. ( 2.1 ) Patients considered opioid-tolerant are those taking, for one week or longer, at least 60 mg of morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg of oral oxycodone per day, 8 mg of oral hydromorphone per day, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid. ( 2.1 ) Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals. Reserve titration to higher doses of MS CONTIN for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. ( 2.1 , 5 ) Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse. ( 2.1 , 5.1 ) Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with MS CONTIN. Consider this risk when selecting an initial dose and when making dose adjustments. ( 2.1 , 5.2 ) Instruct patients to swallow MS CONTIN tablets intact and not to cut, break, chew, crush, or dissolve MS CONTIN (risk of potentially fatal dose). ( 2.1 , 5.1 ) Discuss opioid overdose reversal agents and options for acquiring them with the patient and/or caregiver, both when initiating and renewing treatment with MS CONTIN, especially if the patient has additional risk factors for overdose, or close contacts at risk for exposure and overdose. ( 2.2 , 5.1 , 5.2 , 5.3 ) MS CONTIN is administered orally once every 8 or 12 hours. ( 2.3 ) For patients who are not opioid tolerant, initiate with 15 mg tablets orally every 8 to 12 hours. ( 2.3 ) Periodically reassess patients receiving MS CONTIN to evaluate the continued need for opioid analgesics to maintain pain control, for the signs or symptoms of adverse reactions, and for the development of addiction, abuse, or misuse. ( 2.4 ) Do not rapidly reduce or abruptly discontinue MS CONTIN in a physically dependent patient because rapid reduction or abrupt discontinuation of opioid analgesics has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. ( 2.5 , 5.14 ) 2.1 Important Dosage and Administration Instructions MS CONTIN should be prescribed by healthcare professionals who are knowledgeable about the use of extended-release/long-acting opioids and how to mitigate the associated risks. MS CONTIN 100 mg and 200 mg tablets, a single dose greater than 60 mg, or a total daily dose greater than 120 mg, are only for use in patients in whom tolerance to an opioid of comparable potency has been established. Patients considered opioid-tolerant are those taking, for one week or longer, at least 60 mg morphine per day, 25 mcg transdermal fentanyl per hour, 30 mg oral oxycodone per day, 8 mg oral hydromorphone daily, 25 mg oral oxymorphone per day, 60 mg oral hydrocodone per day, or an equianalgesic dose of another opioid. Use the lowest effective dosage for the shortest duration of time consistent with individual patient treatment goals [see Warnings and Precautions (5) ]. Because the risk of overdose increases as opioid doses increase, reserve titration to higher doses of MS CONTIN for patients in whom lower doses are insufficiently effective and in whom the expected benefits of using a higher dose opioid clearly outweigh the substantial risks. Initiate the dosing regimen for each patient individually, taking into account the patient's underlying cause and severity of pain, prior analgesic treatment and response, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1) ]. Respiratory depression can occur at any time during opioid therapy, especially when initiating and following dosage increases with MS CONTIN. Consider this risk when selecting an initial dose and when making dose adjustments [see Warnings and Precautions (5.2) ]. MS CONTIN is administered orally once every 8 or 12 hours. Instruct patients to swallow MS CONTIN tablets whole. Crushing, chewing, or dissolving MS CONTIN tablets will result in uncontrolled delivery of morphine and can lead to overdose or death [see Warnings and Precautions (5.1) ]. 2.2 Patient Access to an Opioid Overdose Reversal Agent for the Emergency Treatment of Opioid Overdose Inform patients and caregivers about opioid overdose reversal agents (e.g., naloxone, nalmefene). Discuss the importance of having access to an opioid overdose reversal agent, especially if the patient has risk factors for overdose (e.g., concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose) or if there are household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose. The presence of risk factors for overdose should not prevent the management of pain in any patient [see Warnings and Precautions (5.1 , 5.2 , 5.3) ] . Discuss the options for obtaining an opioid overdose reversal agent (e.g., prescription, over-the-counter, or as part of a community-based program) [see Warnings and Precautions (5.2) ]. There are important differences among the opioid overdose reversal agents, such as route of administration, product strength, approved patient age range, and pharmacokinetics. Be familiar with these differences, as outlined in the approved labeling for those products, prior to recommending or prescribing such an agent. 2.3 Initial Dosage It is safer to underestimate a patient's 24-hour oral morphine dosage and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral morphine dosage and manage an adverse reaction due to an overdose. While useful tables of opioid equivalents are readily available, there is inter-patient variability in the potency of opioid drugs and opioid formulations. Frequently reevaluate patients for signs and symptoms of opioid withdrawal and for signs of oversedation/toxicity after converting patients to MS CONTIN. Use of MS CONTIN in Patients who are not Opioid Tolerant The starting dose for patients who are not opioid tolerant is MS CONTIN 15 mg orally every 8 to 12 hours. Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression [see Warnings and Precautions (5.2) ] . Conversion from Other Oral Morphine Formulations to MS CONTIN Patients receiving other oral morphine formulations may be converted to MS CONTIN by administering one-half of the patient's 24-hour requirement as MS CONTIN on an every-12-hour schedule or by administering one-third of the patient's daily requirement as MS CONTIN on an every-8-hour schedule. Conversion from Parenteral Morphine or Other Parenteral Opioid Analgesics to MS CONTIN When converting from parenteral morphine or other parenteral non-morphine opioids to MS CONTIN, consider the following general points: Parenteral to oral morphine ratio : Between 2 to 6 mg of oral morphine may be required to provide analgesia equivalent to 1 mg of parenteral morphine. Typically, a dose of morphine that is approximately three times the previous daily parenteral morphine requirement is sufficient. Other parenteral non-morphine opioid analgesics to oral morphine ratios : Specific recommendations are not available because of a lack of systematic evidence for these types of analgesic substitutions. Published relative potency data are available, but such ratios are approximations. In general, begin with half of the estimated daily morphine requirement as the initial dose, managing inadequate analgesia by supplementation with immediate-release morphine. Conversion from Methadone to MS CONTIN Regular evaluation is of particular importance when converting methadone to other opioid agonists. The ratio between methadone and other opioid agonists may vary widely as a function of previous dose exposure. Methadone has a long half-life and can accumulate in the plasma. Conversion from Other Oral Opioid Analgesics to MS CONTIN When MS CONTIN therapy is initiated, discontinue all opioid analgesics other than those used on an as needed basis for breakthrough pain when appropriate. There are no established conversion ratios for conversion from other opioid analgesics to MS CONTIN defined by clinical trials. Initiate dosing using MS CONTIN 15 mg orally every 8 to 12 hours. 2.4 Titration and Maintenance of Therapy Individually titrate MS CONTIN to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving MS CONTIN to assess the maintenance of pain control, signs and symptoms of opioid withdrawal, and other adverse reactions, as well as to reassess for the development of addiction, abuse, or misuse [see Warnings and Precautions (5.1 , 5.14) ] . Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. During use of opioid therapy for an extended period of time, periodically reassess the continued need for the use of opioid analgesics. Patients who experience breakthrough pain may require a dosage adjustment of MS CONTIN or may need rescue medication with an appropriate dose of an immediate-release analgesic. If the level of pain increases after dose stabilization, attempt to identify the source of increased pain before increasing the MS CONTIN dosage. If after increasing the dosage, unacceptable opioid- related adverse reactions are observed (including an increase in pain after a dosage increase), consider reducing the dosage [see Warnings and Precautions (5) ]. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions. Because steady-state plasma concentrations are approximated in 1 day, MS CONTIN dosage adjustments may be done every 1 to 2 days. 2.5 Dosage Modifications with Concomitant Use of Central Nervous System Depressants If the patient is currently taking a central nervous system (CNS) depressant and the decision is made to begin MS CONTIN, start with the lowest possible dose, 15 mg every 12 hours, monitor patients for signs of respiratory depression, sedation, and hypotension, and consider using a lower dosage of the concomitant CNS depressant [see Warnings and Precautions (5.3) , Drug Interactions (7) ]. 2.6 Safe Reduction or Discontinuation of MS CONTIN Do not rapidly reduce or abruptly discontinue MS CONTIN in patients who may be physically dependent on opioids. Rapid reduction or abrupt discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid reduction or abrupt discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances. When a decision has been made to decrease the dose or discontinue therapy in an opioid dependent patient taking MS CONTIN, there are a variety of factors that should be considered, including the total daily dose of opioid (including MS CONTIN) the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate, and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with co-morbid pain and substance use disorders may benefit from referral to a specialist. There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on MS CONTIN who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper. It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms include 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. If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, evaluate patients for any changes in mood, emergence of suicidal thoughts, or use of other substances. When managing patients taking opioid analgesics, particularly those who have been treated for an extended period of time and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic [see Warnings and Precautions (5.14) , Drug Abuse and Dependence (9.3) ].

See official label

1 INDICATIONS AND USAGE MS CONTIN is indicated for the management of severe and persistent pain that requires an opioid analgesic and that cannot be adequately treated with alternative options, including immediate-release opioids.