DOSAGE AND ADMINISTRATION
KADIAN® may be administered once or twice
daily.
KADIAN
®
capsules should be swallowed whole.
The pellets in KADIAN
®
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, KADIAN® 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 and 200 mg capsules are for use only in
opioid-tolerant patients.
KADIAN
®
is 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.
KADIAN
®
is 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 KADIAN® 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 KADIAN® 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 KADIAN®, 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;
- concurrent medication;
- the type and severity of the patient's pain.
Care should be taken to use low initial doses of
KADIAN
®
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 KADIAN®
Patients on other oral morphine formulations may be converted to
KADIAN® by administering one-half of the patient's total
daily oral morphine dose as KADIAN® capsules every 12
hours (twice-a-day) or by administering the total daily oral morphine dose as
KADIAN® capsules every 24 hours (once-a-day). KADIAN® should not be given more frequently than every 12
hours.
Conversion from Parenteral Morphine or
Other Parenteral or Oral Opioids to KADIAN®
KADIAN® 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 2-6 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 KADIAN® 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 KADIAN®.
Use of KADIAN® as
the First Opioid Analgesic
There has been no evaluation of KADIAN® 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. KADIAN® is 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.
KADIAN® 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 KADIAN®
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, KADIAN®
pellets sprinkled over apple sauce were found to be bioequivalent to KADIAN® 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.
- Use immediately.
- 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 KADIAN® 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 KADIAN
®
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 KADIAN® is 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
KADIAN® should not be reduced below 12 hours.
Cessation of Therapy
When the patient no longer requires therapy with
KADIAN
®
capsules, doses should be tapered gradually to prevent signs and symptoms of
withdrawal in the physically dependent patient.
Conversion from KADIAN® to Other Extended-Release Oral Morphine Formulations
KADIAN® is not bioequivalent to other
extended-release morphine preparations. Although for a given dose the same
total amount of morphine is available from KADIAN® as
from morphine solution or extended-release morphine tablets, the slower release
of morphine from KADIAN® results in reduced maximum and
increased minimum plasma morphine concentrations than with shorter acting
morphine products. Conversion from KADIAN® to the same
total daily dose of 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 KADIAN® to Parenteral Opioids
When converting a patient from KADIAN® 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
KADIAN®, one would take the 24 hour KADIAN® 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 KADIAN® 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
KADIAN® 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 KADIAN® capsules that are no longer needed.
KADIAN® 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.
KADIAN® consists of closed hard gelatin capsules
containing polymer coated morphine sulfate pellets that pose no known handling
risk to health care workers. KADIAN® Capsules are liable
to diversion and misuse both by the general public and health care workers, and
should be handled accordingly.
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