Hydromorphone extended release

Generic Name hydromorphone extended-release Proprietary Name Jurnista (OROS Push-Pull technology)... 

Vasili, V., S. Harris, A. El-Tahtawy, D. Wu, et al., Clinical pharmacology and pharmacokinetics of once-daily hydromorphone hydrochloride extended-release capsules, J. Clin. Pharmacol., 45(5), 547-554, 2005. 

Package insert. Extended release hydromorphone capsules. Purdue Pharma L. P. Stamford, CT, September 2004. 

In general the opioid analgesics can enhance the CNS depressant effects of alcohol, which has been fatal in some cases this appears to be a particular problem with dextropropoxyphene. Alcohol has been associated with rapid release of hydromorphone and morphine from extended-release preparations, which could result in potentially fatal doses. Acute administration of alcohol and methadone appears to increase the blood levels of methadone. The bioavailability of dextropropoxyphene is increased by alcohol... 

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-... 

Oral hydromorphone has a bioavailability of 62% regardless of whether it is given as regular hydromorphone or extended-release capsules. Food has no effect on peak levels. The drug is 20% protein-bound. The two distribution half-lives are 1.3 and 14.7 minutes. The volume of distribution is 4 L/kg [1,2]. 

Hydromorphone is primarily conjugated in the liver. Its metabolites are dihydroisomorphine and dihydromorphine. Excretion via the kidneys occurs up to 13% as unchanged parent compound, and 22-51% as conjugated hydromorphone. Total body clearance is 1.66 L/min. The elimination half-life is about 2.5 hours for the immediate-release compound and the intravenously administered drug, and about 19 hours for the extended-release drug [1,4]. 

Hydromorphone is easily available and titrateable, inexpensive (except extended release), and well tolerated. It causes less pruritus than morphine. It is equivocal whether it causes less nausea in cases where substantial doses are administered. Hydromorphone can be used in a multimodal approach to treat both acute and chronic pain. It carries less risk of toxic metabolites when compared to morphine and meperidine in patients with renal disease. Overdoses are readily treated with the antagonist naloxone. 

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. 

The adverse effects of extended-release hydromorphone are similar to other opioid medications with constipation, nausea, vomiting, pruritus, and urticaria being common. Other possible side effects include confusion, somnolence, euphoria, and respiratory depression. Respiratory depression is the most dangerous side effect of hydromorphone as it may result in hypoxia, coma, and death. Hydromophone should be used with caution in patients taking other CNS depressant medications. High doses of hydromorphone can result in the accumulation of neuroexcita-tory metabolites which may cause seizures and myoclonus. One advantage over morphine is that hepatic metabolites of hydromorphone have minimal analgesic or respiratory depressant activity. 

Extended-release hydromorphone, like other opioid-based medications, has a strong risk of physical dependence and abuse. In this regard the FDA labels hydromorphone as a Category C [3]. 

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]. 

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. 

Hydromorphone is more potent, has better oral absorption characteristics, and is more soluble than morphine, but its overall pharmacologic profile parallels that of morphine. A sustained-release hydromorphone product has recently become available. Oxymorphone can be administered rectally and by injection. Although it is more potent than morphine, it offers no real pharmacologic advantages. Levor-phanol has an extended half-life, bnt its overall therapeutic effects are similar to those of morphine. 

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