"The the European Medicines Agency's (EMA's) Pharmacovigilance Risk Assessment Committee (PRAC) will review the risks and benefits of modified- and prolonged-release paracetamol (acetaminophen) tablets, the agency said today.
PALLADONE is indicated for the management of pain in opioid-tolerant patients severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
Patients considered opioid tolerant are those who are receiving, for one week or longer, at least 60 mg oral morphine per day, 25 mcg transdermal fentanyl/hour, 30 mg oral oxycodone/day, 8 mg oral hydromorphone/day, 25 mg oral oxymorphone/day or an equianalgesic dose of another opioid.
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, reserve PALLADONE 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.
- PALLADONE is not indicated as an as-needed (prn) analgesic.
DOSAGE AND ADMINISTRATION
PALLADONE should be prescribed only by healthcare professionals who are knowledgeable in the use of potent opioids for the management of chronic pain.
Due to the risk of respiratory depression, PALLADONE is only indicated for use in patients who are already opioid-tolerant. Discontinue or taper all other extended-release opioids when beginning PALLADONE therapy. As PALLADONE is only for use in opioid-tolerant patients, do not begin any patient on PALLADONE as the first opioid.
Patients considered opioid-tolerant are those who are taking at least 60 mg of morphine daily, or at least 30 mg of oral oxycodone daily, or at least 8 mg of oral hydromorphone daily or an equianalgesic dose of another opioid for a week or longer.
Initiate the dosing regimen for each patient individually; taking into account the patient's prior analgesic treatment experience and risk factors for addiction, abuse, and misuse [see WARNINGS AND PRECAUTIONS]. Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy with PALLADONE [see WARNINGS AND PRECAUTIONS].
PALLADONE extended-release capsules must be taken whole. Crushing, chewing, or dissolving PALLADONE capsules will result in uncontrolled delivery of hydromorphone and can lead to overdose or death [see WARNINGS AND PRECAUTIONS].
Conversion from Other Oral Opioids to PALLADONE
Discontinue all other around-the-clock opioid drugs when PALLADONE therapy is initiated.
While useful tables of opioid equivalents are readily available, there is substantial inter-patient variability in the relative potency of different opioid drugs and products. As such, it is preferable to underestimate a patient's 24-hour oral hydromorphone requirements and provide rescue medication (e.g., immediate-release opioid) than to overestimate the 24-hour oral hydromorphone requirements which could result in adverse reaction.
In a PALLADONE clinical trial with an open-label titration period, patients were converted from their prior opioid to PALLADONE using the Table 1 as a guide for the initial PALLADONE dose. The recommended starting dose of PALLADONE is 50% of the calculated estimate of daily hydromorphone requirement. Calculate the estimated daily hydromorphone requirement using Table 1.
Consider the following when using the information in Table 1:
- This is not a table of equianalgesic doses.
- The conversion factors in this table are only for the conversion from one of the listed oral opioid analgesics to PALLADONE.
- The table cannot be used to convert from PALLADONE to another opioid. Doing so will result in an overestimation of the dose of the new opioid and may result in fatal overdose.
Table 1: Conversion Factors to PALLADONE*
|Prior Oral Opioid||Approximate Oral Conversion Factor|
To calculate the estimated PALLADONE dose using Table 1:
- For patients on a single opioid, sum the current total daily dose of the opioid and then multiply the total daily dose by the conversion factor to calculate the approximate oral hydromorphone daily dose.
- For patients on a regimen of more than one opioid, calculate the approximate oral hydromorphone dose for each opioid and sum the totals to obtain the approximate total hydromorphone daily dose.
- For patients on a regimen of fixed-ratio opioid/non-opioid analgesic products, use only the opioid component of these products in the conversion.
Always round the dose down, if necessary, to the appropriate PALLADONE strength(s) available.
Example conversion from a single opioid to PALLADONE:
Step 1: Sum the total daily dose of the opioid
- 30 mg of oxycodone 2 times = 60 mg total daily dose of oxycodone
Step 2: Calculate the approximate equivalent dose of oral hydromorphone based on the total daily dose of the current opioid using Table 1
- 60 mg total daily dose of oxycodone x Conversion Factor of 0.25 =15 mg of oral hydromorphone daily
Step 3: Calculate the approximate starting dose of PALLADONE to be given every 24 hours, which is 50% of the calculated oral hydromorphone dose. Round down, if necessary, to the appropriate PALLADONE capsule strengths available.
- 50 % of 15 mg is an initial dose of 6 mg of PALLADONE once daily
- Adjust individually for each patient
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 or for signs of over-sedation/toxicity after converting patients to PALLADONE.
Conversion from Transdermal Fentanyl to PALLADONE
Eighteen hours following the removal of the transdermal fentanyl patch, PALLADONE treatment can be initiated. To calculate the 24-hour PALLADONE dose, use a conversion factor of 25 mcg/hr fentanyl transdermal patch to 12 mg of PALLADONE. Then reduce the PALLADONE dose by 50%.
Step 1: Identify the dose of transdermal fentanyl.
- 75 mg of transdermal fentanyl
Step 2: Use the conversion factor of 25 mcg/hr fentanyl transdermal patch to 12 mg of PALLADONE.
- 75 mg of transdermal fentanyl : 36 mg total daily dose of PALLADONE
Step 3: Calculate the approximate starting dose of PALLADONE to be given every 24 hours, which is 50% of the converted dose. Round down, if necessary, to the appropriate PALLADONE tablet strengths available.
- 50% of 36 mg results in an initial dose of 18 mg, which would be rounded down to 16 mg of PALLADONE once daily
- Adjust individually for each patient
Conversion from Methadone to PALLADONE
Close monitoring is of particular importance when converting from 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.
Titration And Maintenance Of Therapy
Individually titrate PALLADONE to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving PALLADONE to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse. 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 chronic therapy, periodically reassess the continued need for opioid analgesics.
Plasma levels of PALLADONE are sustained for 18 to 24 hours. Dosage adjustments of PALLADONE may be made in increments of 4 to 8 mg every 3 to 4 days as needed to achieve adequate analgesia.
Patients who experience breakthrough pain may require a dose increase of PALLADONE, 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 PALLADONE dose.
If unacceptable opioid-related adverse reactions are observed, the subsequent doses may be reduced. Adjust the dose to obtain an appropriate balance between management of pain and opioid-related adverse reactions.
Discontinuation Of PALLADONE
When a patient no longer requires therapy with PALLADONE, taper doses gradually, by 25% to 50% every 2 or 3 days down to a dose of 12 mg before discontinuation of therapy, to prevent signs and symptoms of withdrawal in the opioid-tolerant patient.
To dispose of unused PALLADONE flush all remaining capsules down the toilet or remit to authorities at a certified drug take-back program.
Start patients with moderate hepatic impairment on 25% of the PALLADONE dose that would be prescribed for patients with normal hepatic function. Closely monitor patients with moderate hepatic impairment for respiratory and central nervous system depression during initiation of therapy with PALLADONE and during dose titration. Use of alternate analgesics is recommended for patients with severe hepatic impairment [see Use in Specific Populations].
Start patients with moderate renal impairment on 50% and patients with severe renal impairment on 25% of the PALLADONE dose that would be prescribed for patients with normal renal function. Closely monitor patients with renal impairment for respiratory and central nervous system depression during initiation of therapy with PALLADONE and during dose titration. As PALLADONE is only intended for once daily administration, consider use of an alternate analgesic that may permit more flexibility with the dosing interval in patients with severe renal impairment [see Use in Specific Populations].
Administration Of PALLADONE
Instruct patients to swallow PALLADONE capsules intact. The capsules are not to be crushed, dissolved, or chewed due to the risk of rapid release and absorption of a potentially fatal dose of hydromorphone [see WARNINGS AND PRECAUTIONS].
Dosage Forms And Strengths
PALLADONE extended-release capsules are available in 12 mg, 16 mg, 24 mg or 32 mg dosage strengths.
The 12 mg extended-release capsules are cinnamon-colored capsules imprinted with “P-XL” on the cap and “12 mg” on the body.
The 16 mg extended-release capsules are pink, imprinted with “P-XL” on the cap and 16 mg on the body.
The 24 mg extended-release capsules are blue, imprinted with “P-XL” on the cap and 24 mg on the body.
The 32 mg extended-release capsules are white, imprinted with “P-XL” on the cap and 32 mg on the body.
Storage And Handling
PALLADONE (hydromorphone hydrochloride) extended-release capsules are supplied as follows:
12 mg: cinnamon-colored capsules imprinted with “P-XL” on the cap and “12 mg” on the body and available as follows:
60 capsules, opaque plastic bottle ....…………. NDC 42858-008-06
20 capsules, Unit Dose (2 X 10) ......…………. NDC 42858-008-11
16 mg: pink-colored capsules imprinted with “P-XL” on the cap and “16 mg” on the body and available as follows:
60 capsules, opaque plastic bottle ....…………. NDC 42858-027-06
20 capsules, Unit Dose (2 X 10) ......…………. NDC 42858-027-11
24 mg: blue-colored capsules imprinted with “P-XL” on the cap and “24 mg” on the body and available as follows:
60 capsules, opaque plastic bottle ...…………. NDC 42858-039-06
20 capsules, Unit Dose (2 X 10) .....…………. NDC 42858-039-11
32 mg: white capsules imprinted with “P-XL” on the cap and “32 mg” on the body and available as follows:
60 capsules, opaque plastic bottle ..…………. NDC 42858-204-06
20 capsules, Unit Dose (2 X 10) ...…………. NDC 42858-204-11
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].
Avoid temperatures above 40°C (104°F) [See USP Excessive Heat]
Dispense in a tight, light-resistant container.
DEA ORDER FORM REQUIRED.
Marketed by: Rhodes Pharmaceuticals L.P. Coventry, RI 02816. Manufactured by: The PF Laboratories Inc. Totowa, New Jersey, 07512. Revision: April 2014This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 5/1/2014
Additional Palladone Information
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