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2 DOSAGE AND ADMINISTRATION
Selection of patients for treatment with morphine sulfate should
be governed by the same principles that apply to the use of similar opioid
analgesics. Physicians should individualize treatment in every case, using
non-opioid analgesics, opioids on an as needed basis and/or combination
products, and chronic opioid therapy in a progressive plan of pain management
such as outlined by the World Health Organization and Federation of State
Medical Boards Model Guidelines.
Care should be taken to use low initial doses of EMBEDA in
patients who are not already opioid-tolerant, especially those who are receiving
concurrent treatment with muscle relaxants, sedatives, or other CNS active
medications.
The 100 mg/4 mg capsules are for use only in opioid-tolerant
patients.
EMBEDA is to be swallowed whole or the contents of the capsules sprinkled on
apple sauce and taken by mouth. The pellets in the capsules are not to be
crushed, dissolved, or chewed before swallowing.
2.1 Initiating Therapy with EMBEDA
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 EMBEDA, attention should be
given to:
1) the total daily dose, potency, and kind of opioid the patient has been
taking previously;
2) 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);
3) the patient's degree of opioid
experience and opioid tolerance;
4) the general condition and medical status
of the patient;
5) concurrent medication;
6) the type and severity of the
patient's pain.
The following dosing recommendations can be considered approaches to what is
actually a series of clinical decisions over time in the management of the pain
of an individual patient:
Use of EMBEDA as the First Opioid
Analgesic
The lowest dose of EMBEDA should be used as the initial opioid analgesic in
patients with chronic pain. Patients may subsequently be titrated to a once or
twice a day dosage which adequately manages their pain.
Conversion from Other Oral Morphine
Formulations to EMBEDA
Patients on other oral morphine formulations may be converted to EMBEDA by
administering one-half of the patient's total daily oral morphine dose as EMBEDA
every 12 hours (twice-a-day) or by administering the total daily oral morphine
dose as EMBEDA every 24 hours (once-a-day). EMBEDA should not be given more
frequently than every 12 hours.
Conversion from Oral Opioids,
Parenteral Morphine, or Other Parenteral Opioids to EMBEDA
EMBEDA 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 inter-patient
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 2-6 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 Oral or Parenteral 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.
The first dose of EMBEDA may be taken with the last dose of any
immediate-release (short-acting) opioid medication due to the extended-release
characteristics of EMBEDA.
2.2 Individualization of Dosage
Patients may develop some degree of tolerance, requiring dosage
adjustment until they have achieved their individual balance between effective
analgesia and opioid side effects such as confusion, sedation, and constipation.
- EMBEDA should be titrated no more frequently than every-other-day to allow
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 exhibit signs of excessive opioid side effects such as sedation
should have their dose reduced.
- Patients who experience inadequate analgesia on once-daily dosing should be
switched to twice-a-day.
- EMBEDA should not be dosed more frequently than every 12 hours.
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.
2.3 Alternative Methods of Administration
Patients who have difficulty swallowing whole capsules or tablets
may benefit from an alternative method of administration. EMBEDA pellets may be
sprinkled over apple sauce. Other foods have not been tested and should not be
substituted for apple sauce.
- Sprinkle the pellets onto a small amount of apple sauce and use immediately.
- The patient must be cautioned not to chew the pellets [see WARNINGS
AND PRECAUTIONS (5) ].
- Rinse mouth to ensure all pellets have been swallowed.
- Patients should consume entire portion and should not divide apple sauce
into separate doses.
Do not administer EMBEDA pellets through a nasogastric or gastric
tubes.
2.4 Maintenance of Therapy
Continual re-evaluation of the patient receiving morphine sulfate
is important, with special attention to the maintenance of pain control and the
relative incidence of side effects associated with therapy. If the level of pain
increases, effort should be made to identify the source of increased pain, while
adjusting the dose as described above to decrease the level of pain. During
chronic therapy, especially for non-cancer-related pain (or pain associated with
other terminal illnesses), the continued need for the use of opioid analgesics
should be re-assessed as appropriate.
2.5 Cessation of Therapy
In general, EMBEDA should not be abruptly discontinued. However,
EMBEDA, like other opioids, can be safely discontinued without the development
of withdrawal symptoms by slowly tapering the daily dose.
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