Hydromorphone extended release formulations

Pharmacokinetic data in healthy subjects has shown that consuming alcohol with a particular 24-hour extended-release formulation of hydromorphone (Palladone XL Capsules Purdue Pharma, USA) could lead to rapid release (dose dumping) and absorption of a potentially fatal dose of hydromorphone. Although no reports of serious problems had been re-... 

Weinstein SM. A new extended release formulation (OROS ) of hydromorphone in the management of pain. Iher Clin Risk Manage 2009 5 75-80. 

Drover DR, Angst MS, Valle M, Ramaswamy B, Naidu S, Stanski DR, Verotta D. Input characteristics and bioavailability after administration of immediate and a new extended-release formulation of hydromorphone in healthy volunteers. Anesthesiology 2002 97(4) 827-36. 

Hydrocodone has a half-life of 3.8 boms, peak effect at 1.3 hours, and a duration of 4.6 hours. It is metabolized by the liver and excreted primarily in urine. Hydrocodone is oxidized to hydromorphone by cytochrome P450 2D6. The extended-release formulation has measurably different pharmacokinetics following a single dose of 1,2 or 3 HC/ APAP CR tablet(s), the mean maximum plasma concentration (C ) ranged from 13.3 to 36.8 ng/mL for HC and 2.01 to 6.68 ng/mL for APAP. The mean time to reach (T ) was 6.0-6.7 hours for HC and 1.1-1.3 hours for APAP. Following twice-daily dosing of 2 HC/APAP CR tablets for 3 days, steady-state HC/APAP concentrations were attained by 24 hours [3,4]. The mean on day 3 was 37.0 ng/mL for HC and 4.96 ng/mL for APAP. Systemic exposures of HC and APAP demonstrated a dose-proportional increase from one to three tablets. Steady-state concentrations were reached by 24 hours with minimal accumulation following twice-daily administration. Thus, it can be taken every 12 hours [4]. 

Recently two new formulations of extended-release hydromorphone, Palladone and Exalgo , have been... 

Two formulations of extended-release hydromorphone have been evaluated and filed for FDA approval in the USA. These formulations have been marketed under the names Palladone , manufactured by Purdue Pharma Inc., and Exalgo , produced by Neu-romed Pharmaceuticals Inc. Palladone was initially approved for sale in the USA in 2004, but was voluntarily withdrawn from the market due to safety concerns. Exalgo is currently in the final stages of FDA approval as a once-daily administered analgesic for the management of chronic pain. 

Toxicity a previous formulation of extended-release hydromorphone marketed under the name Palladone utilized a distinct technology but was pulled from... 

Palangio M, Northfelt D, Portenoy R, BrookofF D, Doyle R, Dornseif B, Damask M. Dose conversion and titration with a novel, once-daUy, OROS osmotic technology, extended-release hydromorphone formulation in the treatment of chronic malignant or nonmalignant pain. / Pain Symptom Manage 2002 23(5) 355-368. 

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