Morphine Sulfate

MORPHINE SULFATE- morphine sulfate tablet, film coated, extended release
Lupin Pharmaceuticals,Inc.

1 INDICATIONS AND USAGE

Morphine sulfate extended-release tablets is indicated for the management of pain severe enough to require daily, around-the-clock, 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 [see Warnings and Precautions (5.1)] , reserve morphine sulfate extended-release tablets 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.
• Morphine sulfate extended-release tablets is not indicated as an as-needed (prn) analgesic.

2 DOSAGE AND ADMINISTRATION

2.1 Important Dosage and Administration Instructions

Morphine sulfate extended-release tablets should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.

Morphine sulfate extended-release tablets100 mg and 200 mg capsules, 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 consistent with individual patient treatment goals [see Warnings and Precautions (5)].
• Initiate the dosing regimen for each patient individually, taking into account the patient’s severity of pain, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see Warnings and Precautions (5.1)].
• Monitor patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with morphine sulfate extended-release tablets and adjust the dosage accordingly [see Warnings and Precautions (5.2)].

Instruct patients to swallow morphine sulfate extended-release tablets whole [see Patient Counseling Information (17)]. Crushing, chewing, or dissolving morphine sulfate extended-release tablets will result in uncontrolled delivery of morphine and can lead to overdose or death [see Warnings and Precautions (5.1)].

Morphine sulfate extended-release tablets is administered orally once every 8 or 12 hours.

2.2 Initial Dosage

Use of morphine sulfate extended-release tablets as the First Opioid Analgesic (opioid-naïve patients)

Initiate treatment with morphine sulfate extended-release tablets with 15 mg tablets orally every 8 or 12 hours.

Use of morphine sulfate extended-release tablets in Patients who are not Opioid Tolerant (opioid non-tolerant patients)

The starting dose for patients who are not opioid tolerant is morphine sulfate extended-release tablets15 mg orally every 12 hours.

Use of higher starting doses in patients who are not opioid tolerant may cause fatal respiratory depression.

Conversion from Other Oral Morphine to Morphine sulfate extended-release tablets

Patients receiving other oral morphine formulations may be converted to morphine sulfate extended-release tablets by administering one-half of the patient’s 24-hour requirement as morphine sulfate extended-release tablets on an every-12-hour schedule or by administering one-third of the patient’s daily requirement as morphine sulfate extended-release tablets on an every-8-hour schedule.

Conversion from Other Opioids to Morphine sulfate extended-release tablets

Discontinue all other around-the-clock opioid drugs when morphine sulfate extended-release tablets therapy is initiated.

There are no established conversion ratios for conversion from other opioids to morphine sulfate extended-release tablets defined by clinical trials. Initiate dosing using morphine sulfate extended-release tablets 15 mg orally every 8 to 12 hours.

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. Close observation and frequent titration are warranted until pain management is stable on the new opioid. Monitor patients for signs and symptoms of opioid withdrawal and for signs of oversedation/toxicity after converting patients to morphine sulfate extended-release tablets.

Conversion from Parenteral Morphine or Other Opioids (Parenteral or Oral) to Morphine sulfate extended-release tablets

When converting from parenteral morphine or other non-morphine opioids (parenteral or oral) to Morphine sulfate extended-release tablets, 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 or oral non-morphine opioids 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 Morphine sulfate extended-release tablets

Close monitoring 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.