Alert for Healthcare
Professionals
Hydromorphone Hydrochloride Extende-Release Capsules (marketed as Palladone)
This product is not currently available for purchase in the U.S. |
FDA ALERT [7/2005]: Alcohol-Palladone Interaction
Purdue Pharma has agreed to FDA’s
request that they voluntarily suspend sales and marketing of
Palladone in the United States. At this time, the Agency has
concluded that the overall risk versus benefit profile of
Palladone is unfavorable due to a potentially fatal interaction
with alcohol.
Pharmacokinetic data indicate that the co-ingestion of
Palladone and alcohol results in dangerous increases in the peak
plasma concentrations of hydromorphone. These elevated levels may
be lethal, even in opioid tolerant patients.
This information reflects FDA’s
current analysis of data available to FDA concerning this drug.
FDA intends to update this sheet when additional information or
analyses become available.
To
report any unexpected adverse or serious events associated with the
use of this drug, please contact the FDA MedWatch program at
1-800-FDA-1088 or
http://www.fda.gov/medwatch/report/hcp.htm
Recommendations
FDA recommends that healthcare
providers who have prescribed Palladone contact affected patients,
discuss how to use any remaining drug (that is, to use without any
concomitant alcohol intake), and prescribe an appropriate
substitute.
Data Summary
A pharmacokinetic study in healthy
subjects showed that co-ingestion of a 12-mg Palladone capsule with
240 mL (8 ounces) of 40% (80 proof) alcohol resulted in an average
peak hydromorphone concentration approximately six times greater
than when taken with water. One subject in this study experienced a
16-fold increase when the drug was ingested with 40% alcohol
compared with water. In certain subjects, 8 ounces of 4% alcohol
(equivalent to 2/3 of a typical serving of beer) resulted in almost
twice the peak plasma hydromorphone concentration than when the drug
was ingested with water.
This pharmacokinetic study was an open-label,
four-arm, crossover design study and included twenty-four healthy
adult subjects who were tested under fasted conditions and 24
healthy adult subjects who were tested under standardized fed
conditions. Subjects were pretreated with naltrexone to block the
opiate effects, and then administered one of the following four
treatments:
Group A
Palladone 12 mg + 240 mL of 40%
ethanol
Group B Palladone, 12 mg + 240 mL of
20% ethanol
Group C Palladone, 12 mg + 240 mL of
4% ethanol
Group D Palladone, 12 mg + 240 mL of
water
Plasma was sampled and analyzed for
hydromorphone concentration at appropriate intervals. Each subject
received each of the four treatments, thereby acting as his or her
own control (Group D).
The effects of alcohol co-ingestion were more
marked in the fasted state and are summarized below.
Pharmacokinetic Outcomes Resulting from
Co-ingestion of Palladone with Different Concentrations of Alcohol
(fasted state)
|
|
Ratio 40* |
Ratio 20** |
Ratio 4† |
Cmax‡ |
Mean |
6 |
2 |
1 |
|
Range |
1-16 |
1-6 |
1-2 |
AUC*** |
Mean |
1.3 |
1 |
1 |
|
Range |
0.6-3.4 |
0.4-1.5 |
0.5-1.9 |
*Ratio
of values when co-ingested with 240 mL of 40% ethanol
compared to co-ingestion with 240 mL of water, i.e. if the peak
plasma concentration was 6 ng/mL when administered with alcohol and
1 ng/mL when administered with water, this ratio would be 6
**Ratio
of values (as above) when co-ingested with 240 mL of 20%
ethanol compared to co-ingestion with 240 mL of water
†Ratio
of values (as above) when co-ingested with 240 mL of 4%
ethanol compared to co-ingestion with 240 mL of water
‡Peak
plasma concentration
***Measure
of total drug exposure
In the
fed state, the mean peak plasma concentration ratio (40%
alcohol:water) was 3.5 with a maximum of 6.
In summary, the study showed that ingesting Palladone with alcohol in clinically relevant amounts results in
significantly higher peak plasma concentrations of hydromorphone.
The effect is more pronounced with increasing concentrations of
alcohol and in a fasted state.
The effects of co-ingestion of smaller volumes
and with other concentrations of alcohol has not been studied.
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Date created: July 13, 2005, updated July, 2007 |