Morphine sulfate extended-release capsules may be administered once or twice daily.
Morphine sulfate extended-release capsules should be swallowed whole. The pellets in morphine sulfate extended-release capsules should not be chewed, crushed, or dissolved due to the risk of rapid release and absorption of a potentially fatal dose of morphine.
Alternatively, morphine sulfate extended-release capsules may be administered as a sprinkle on apple sauce or through a 16 French gastrostomy tube (see ALTERNATIVE METHODS OF ADMINISTRATION section).
The 100 mg capsules are for use only in opioid-tolerant patients.
Morphine sulfate extended-release capsules are not indicated for pre-emptive analgesia (administration pre-operatively for the management of post-operative pain), or for pain in the immediate post-operative period (the first 12 to 24 hours following surgery) for patients not previously taking the drug, because its safety in these settings have not been established.
Morphine sulfate extended-release capsules are only indicated for post-operative use if the patient is already receiving the drug prior to surgery or if the postoperative pain is expected to be moderate to severe and persist for an extended period of time.
Patients who are already receiving morphine sulfate extended-release capsules as part of ongoing analgesic therapy may be safely continued on the drug if appropriate dosage adjustments are made considering the procedure, other drugs given, and the temporary changes in physiology caused by the surgical intervention.
Initiating Therapy with Morphine sulfate extended-release Capsules
Physicians should individualize treatment using a progressive plan of pain management such as outlined by the World Health Organization, the American Pain Society and the Federation of State Medical Boards Model Guidelines. Health care professionals should follow appropriate pain management principles of careful assessment and ongoing monitoring.
It is critical to adjust the dosing regimen for each patient individually, taking into account the patient's prior analgesic treatment experience. In the selection of the initial dose of morphine sulfate extended-release capsules, USP, attention should be given to:
the total daily dose, potency and kind of opioid the patient has been taking previously;
the reliability of the relative potency estimate used to calculate the equivalent dose of morphine needed (Note: potency estimates may vary with the route of administration);
the patient's degree of opioid experience and opioid tolerance;
the general condition and medical status of the patient;
the type and severity of the patient's pain.
Care should be taken to use low initial doses of morphine sulfate extended-release capsules in patients who are not already opioid-tolerant, especially those who are receiving concurrent treatment with muscle relaxants, sedatives, or other CNS active medications (see PRECAUTIONS).
During periods of changing analgesic requirements including initial titration, frequent communication is recommended between physician, other members of the healthcare team, the patient, and the caregiver/family.
The following dosing recommendations, therefore, can only be considered suggested approaches to what is actually a series of clinical decisions over time in the management of the pain of an individual patient.
Conversion from Other Oral Morphine Formulations to Morphine sulfate extended-release capsules
Patients on other oral morphine formulations may be converted to morphine sulfate extended-release capsules by administering one-half of the patient's total daily oral morphine dose as morphine sulfate extended-release capsules every 12 hours (twice-a-day) or by administering the total daily oral morphine dose as morphine sulfate extended-release capsules every 24 hours (once-a-day). Morphine sulfate extended-release capsules should not be given more frequently than every 12 hours.
Conversion from Parenteral Morphine or Other Parenteral or Oral Opioids to Morphine sulfate extended-release capsules
Morphine sulfate extended-release capsules can be administered to patients previously receiving treatment with parenteral morphine or other opioids. While there are useful tables of oral and parenteral equivalents in cancer analgesia, there is substantial interpatient variation in the relative potency of different opioid drugs and formulations. For these reasons, it is better to underestimate the patient's 24-hour oral morphine requirement and provide rescue medication, than to overestimate and manage an adverse event. The following general points should be considered:
Parenteral to Oral Morphine Ratio: It may take anywhere from 2 to 6 mg of oral morphine to provide analgesia equivalent to 1 mg of parenteral morphine. A dose of oral morphine three times the daily parenteral morphine requirement may be sufficient in chronic use settings.
Other Parenteral or Oral Opioids to Oral Morphine Sulfate: There is lack of systematic evidence bearing on these types of analgesic substitutions. Therefore, specific recommendations are not possible. Physicians are advised to refer to published relative potency data, keeping in mind that such ratios are only approximate. In general, it is safest to give half of the estimated daily morphine demand as the initial dose, and to manage inadequate analgesia by supplementation with immediate-release morphine. (See discussion which follows.)
The first dose of morphine sulfate extended-release capsules may be taken with the last dose of any immediate-release (short-acting) opioid medication due to the long delay until the peak effect after administration of morphine sulfate extended-release capsules.
Use of morphine sulfate extended-release capsules as the First Opioid Analgesic
There has been no evaluation of morphine sulfate extended-release capsules as an initial opioid analgesic in the management of pain. Because it may be more difficult to titrate a patient to adequate analgesia using an extended-release morphine, it is ordinarily advisable to begin treatment using an immediate-release morphine formulation.
Individualization of Dosage
The best use of opioid analgesics in the management of chronic malignant and non-malignant pain is challenging, and is well described in materials published by the World Health Organization and the Agency for Health Care Policy and Research which are available from Alpharma Pharmaceuticals LLC upon request. Morphine sulfate extended-release capsules, USP are a third step drug which is most useful when the patient requires a constant level of opioid analgesia as a "floor" or "platform" from which to manage breakthrough pain. When a patient has reached the point where comfort cannot be provided with a combination of non-opioid medications (NSAIDs and acetaminophen) and intermittent use of moderate or strong opioids, the patient's total opioid therapy should be converted into a 24 hour oral morphine equivalent.
Morphine sulfate extended-release capsules should be started by administering one-half of the estimated total daily oral morphine dose every 12 hours (twice-a-day) or by administering the total daily oral morphine dose every 24 hours (once-a-day). The dose should be titrated no more frequently than every-other-day to allow the patients to stabilize before escalating the dose. If breakthrough pain occurs, the dose may be supplemented with a small dose (less than 20% of the total daily dose) of a short-acting analgesic. Patients who are excessively sedated after a once-a-day dose or who regularly experience inadequate analgesia before the next dose should be switched to twice-a-day dosing.
Patients who do not have a proven tolerance to opioids should be started only on the 10 mg or 20 mg strength, and usually should be increased at a rate not greater than 20 mg every-other-day. Most patients will rapidly develop some degree of tolerance, requiring dosage adjustment until they have achieved their individual best balance between baseline analgesia and opioid side effects such as confusion, sedation and constipation. No guidance can be given as to the recommended maximal dose, especially in patients with chronic pain of malignancy. In such cases the total dose of morphine sulfate extended-release capsules should be advanced until the desired therapeutic endpoint is reached or clinically significant opioid-related adverse reactions intervene.
Alternative Methods of Administration
In a study of healthy volunteers, morphine sulfate extended-release pellets sprinkled over apple sauce were found to be bioequivalent to morphine sulfate extended-release capsules swallowed whole with apple sauce under fasting conditions. Other foods have not been tested. Patients who have difficulty swallowing whole capsules or tablets may benefit from this alternative method of administration.
Sprinkle the pellets onto a small amount of apple sauce. Apple sauce should be room temperature or cooler.
The patient must be cautioned not to chew the pellets which could result in the immediate release of a potentially dangerous, even fatal dose of morphine.
Rinse mouth to ensure all pellets have been swallowed.
Patients should consume entire portion and should not divide apple sauce into separate doses.
The entire capsule contents may alternatively be administered through a 16 French gastrostomy tube.
Flush the gastrostomy tube with water to ensure that it is wet.
Sprinkle the morphine sulfate extended-release pellets into 10 mL of water.
Use a swirling motion to pour the pellets and water into the gastrostomy tube through a funnel.
Rinse the beaker with a further 10 mL of water and pour this into the funnel.
Repeat rinsing until no pellets remain in the beaker.
THE ADMINISTRATION OF MORPHINE SULFATE EXTENDED-RELEASE PELLETS THROUGH A NASOGASTRIC TUBE SHOULD NOT BE ATTEMPTED.
Considerations in the Adjustment of Dosing Regimens
If signs of excessive opioid effects are observed early in the dosing interval, the next dose should be reduced. If this adjustment leads to inadequate analgesia, that is, if breakthrough pain occurs when morphine sulfate extended-release capsules are administered on an every 24 hours dosing regimen, consideration should be given to dosing every 12 hours. If breakthrough pain occurs on a 12 hour dosing regimen a supplemental dose of a short-acting analgesic may be given. As experience is gained, adjustments in both dose and dosing interval can be made to obtain an appropriate balance between pain relief and opioid side effects. To avoid accumulation the dosing interval of morphine sulfate extended-release capsules should not be reduced below 12 hours.
Cessation of Therapy
When the patient no longer requires therapy with morphine sulfate extended-release capsules, doses should be tapered gradually to prevent signs and symptoms of withdrawal in the physically dependent patient.
Conversion from Morphine Sulfate Extended-Release Capsules to Other Extended-Release Oral Morphine Formulations
Morphine sulfate extended-release capsules are not bioequivalent to other extended-release morphine preparations. Although for a given dose the same total amount of morphine is available from morphine sulfate extended-release capsules as from morphine solution or extended-release morphine tablets, the slower release of morphine from morphine sulfate extended-release capsules results in reduced maximum and increased minimum plasma morphine concentrations than with shorter acting morphine products. Conversion from morphine sulfate extended-release capsules to the same total daily dose of other extended-release morphine preparations may lead to either excessive sedation at peak or inadequate analgesia at trough and close observation and appropriate dosage adjustments are recommended.
Conversion from Morphine Sulfate Extended-Release Capsules to Parenteral Opioids
When converting a patient from morphine sulfate extended-release capsules to parenteral opioids, it is best to calculate an equivalent parenteral dose, and then initiate treatment at half of this calculated value. For example, to estimate the required 24 hour dose of parenteral morphine for a patient taking morphine sulfate extended-release capsules, one would take the 24 hour morphine sulfate extended-release capsules dose, divide by an oral to parenteral conversion ratio of 3, divide the estimated 24 hour parenteral dose into six divided doses (for a four hour dosing interval), then halve this dose as an initial trial.
For example, to estimate the required parenteral morphine dose for a patient taking 360 mg of morphine sulfate extended-release capsules a day, divide the 360 mg daily oral morphine dose by a conversion ratio of 1 mg of parenteral morphine for every 3 mg of oral morphine. The estimated 120 mg daily parenteral requirement is then divided into six 20 mg doses, and half of this, or 10 mg, is then given every 4 hours as an initial trial dose.
This approach is likely to require a dosage increase in the first 24 hours for many patients, but is recommended because it is less likely to cause overdose than trying to establish an equivalent dose without titration.
Safety and Handling
Morphine sulfate extended-release capsules contain morphine sulfate which is a controlled substance under Schedule II of the Controlled Substances Act. Morphine, like all opioids, is liable to diversion and misuse and should be handled accordingly. Patients and their families should be instructed to flush any morphine sulfate extended-release capsules that are no longer needed.
Morphine sulfate extended-release capsules may be targeted for theft and diversion by criminals. 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.
Morphine sulfate extended-release capsules consists of closed hard gelatin capsules containing polymer coated morphine sulfate pellets that pose no known handling risk to health care workers. Morphine sulfate extended-release capsules are liable to diversion and misuse both by the general public and health care workers, and should be handled accordingly.