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`Home Drugs Drug Safety and Availability Postmarket Drug Safety Information for Patients and Providers
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`Drugs
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`Information for Healthcare Professionals: Hydromorphone Hydrochloride Extended-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 ’5 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 using the information at the bottom of the page.
`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 lZ-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 4i
`i
`Ratio 20“
`Ratio 40*
`
`2
`i
`6
`
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`1
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`http ://www.fda. govmrugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandP . ..
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`10/22/2014
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`ENDO - Ex. 2055
`
`Amneal v. Endo
`
`|PR2014-00360
`
`ENDO - Ex. 2055
`Amneal v. Endo
`IPR2014-00360
`
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`Postmarket Drug Safety Information for Patients and Providers > Information for Healthc... Page 2 of 2
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`I
`
`0.5-1.9
`I
`0.4—1.5
`0.6-3.4
`I
`Range
`I
`*Ratio of values when co—ingested with 240 mL of 40% ethanol compared to co—ingestlon 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
`MRatio 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
`
`:Pfak 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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`Page Last Updated: 11/25/2011
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