What is the difference between kadian and oxycontin

Subscribe today for unlimited access to exclusive investigations, breaking news, features and more. But in all the scrutiny of Purdue and OxyContin, the problem of the drug wearing off early was not addressed. In reports to headquarters, they wrote that many physicians were prescribing it for three or even four doses a day. Lawrence Robbins started prescribing OxyContin at his Chicago migraine clinic shortly after it hit the market. But insurance carriers often refused to cover the pharmacy bill for more than two pills a day, he said.

Over the years, he wrote insurance companies more than 25 times on behalf of patients who he believed needed OxyContin more frequently than every 12 hours, he said. In some cases, the insurers relented. When others did not, Robbins switched the patients to another drug.

In this letter, a Purdue regional manager writes that he is concerned about doctors prescribing OxyContin at 8-hour intervals. Sales reps should visit those physicians and convince them to go back to hour dosing, he writes. Data analyzed by company employees showed that one in five OxyContin prescriptions was for use every eight hours, or even more frequently. Purdue held closed-door meetings to retrain its sales force on the importance of hour dosing, according to training documents, some included in sealed court files and others described in FDA files.

In a petition to the FDA, attorneys for the state of Connecticut described the alarm inside Purdue when some doctors began prescribing OxyContin at more frequent intervals. There is no ceiling on the amount of OxyContin a patient can be prescribed, sales reps were to remind doctors, according to the presentation and other training materials. After some physicians began prescribing OxyContin more frequently than every 12 hours, Purdue summoned its sales force to special seminars.

As this presentation shows, company officials were concerned more frequent dosing would hurt business. Higher doses did mean more money for Purdue and its sales reps. Commissions and performance evaluations for the sales force were based in part on the proportion of sales from high-dose pills. In this memo entitled "It's Bonus Time in the Neighborhood," a Purdue sales manager told her staff to talk up stronger doses of OxyContin in conversations with doctors.

In the training materials reviewed by The Times, little was said about the effect of higher doses on patient health. Those on higher doses of opioids are more likely to overdose, according to numerous research studies.

An analysis of the medical records of more than 32, patients on OxyContin and other painkillers in Ontario, Canada, found that one in 32 patients on high doses fatally overdosed.

As a varsity athlete at the University of Central Florida and later a public school teacher, Burgess MacNamara was used to following rules. That changed in when he had knee surgery and his doctor put him on OxyContin. Your whole day revolves around that. Within a month, he was crushing and snorting the pills. Within a year, he was forging prescriptions. He eventually tried heroin, which was cheaper, and other drugs. MacNamara was arrested for forging prescriptions, possession of controlled substances, stealing pills from a school clinic and other drug-fueled crimes.

He lost his teaching career and spent 19 months behind bars. A separate study underwritten by a Purdue competitor, Janssen Pharmaceutica, reached a similar conclusion. In the real world practice of medicine, some doctors turned away from OxyContin entirely.

San Francisco public health clinics stopped dispensing the painkiller in , based in part on feedback from patients who said it wore off after eight hours.

The clinics switched to generic morphine, which has a similar duration and costs a lot less. Mitchell Katz, then head of the San Francisco public health department, said in an interview. One of the plaintiffs was a retired Alabama businessman named H.

Jerry Bodie. His doctor had Bodie on 30 milligrams of OxyContin every eight hours for chronic back pain. A Purdue sales rep persuaded him to switch Bodie to a higher dose every 12 hours, according to a judge's summary of the evidence.

The doctor kept raising the dose, eventually putting Bodie on milligrams a day. Purdue got suits dismissed by asserting, among other defenses, a legal doctrine which shields drug companies from liability when their products are prescribed by trained physicians. Purdue settled other lawsuits on confidential terms.

In a federal suit, Alabama businessman H. Jerry Bodie accused Purdue of overstating the duration of OxyContin, among other complaints. The lawsuit was dismissed. In these legal battles, the company successfully petitioned courts to have evidence sealed, citing the need to protect trade secrets.

In the fall of , in a remote courthouse in Appalachia, the hour dosing issue came close to a public airing. In describing problems with OxyContin, many said the drug wore off hours early. All these efforts failed. Purdue had one final shot at avoiding trial: A motion for summary judgment. Stephens, son of a local coal miner and the first African American elected to the West Virginia circuit court. To make this critical argument, the company tapped Eric Holder Jr. On Oct. Stephens disagreed.

He ruled that there was enough evidence that a jury could find Purdue had made deceptive claims about OxyContin, including how long it lasted. His decision meant that for the first time, questions about OxyContin's duration would be aired at a trial. Sealed evidence would be laid out in public for class-action attorneys, government investigators, doctors and journalists to see. All the evidence under seal would remain confidential.

A week later, Judge Stephens ordered one more document withdrawn from public view: His Nov. This produces a three-dimensional interlocking network of LBG molecules in water [1].

When LBG is mixed with xanthan, a synergistic interaction occurs, which results in the rigid helices of xanthan in solution becoming incorporated into the true gel structure of the LBG molecules.

The interaction can be considered synergistic because the viscosity build that occurs when both polysaccharides are used together is significantly greater weight for weight than either material used alone. Also, when the two polysaccharides are mixed, gel formation develops at ambient temperature [1].

In TIMERx tablets, when a molecular valve is open, the drug can pass out of that part of the gel; but when a valve is closed, drug diffusion is stopped. A valve can be considered open when the intermolecular bonding between xanthan and LBG is either at a minimum or at a maximum e.

For example, a low degree of crosslinking between the polymer chains is likely to cause valves to be open, as there will be a large number of less tortuous channels in the gel. As the polymer chains crosslink, the pores become more tortuous and constricted, leading to valve closure [1]. This system is thought to help ensure reliable and steady drug release over 12 hours.

The retardants control the rate of release of the active ingredient oxycodone, in the case of OxyContin from the tablet matrix [8]. The AcroContin drug delivery system depends on two different types of retardants to control the rate of drug release. The two retarding ingredients are ammonio-methacrylate copolymer, a water-insoluble polymer, and stearyl alcohol, a water-insoluble wax.

Both ingredients are suitable retardants for oxycodone, as oxycodone is water-soluble. The oxycodone in an OxyContin tablet is contained in a homogenous mixture of the active drug oxycodone and retardants, that is, there are not two separate components to a tablet OxyContin does not contain a separate immediate-release component [7]. After ingestion, the GI fluid dissolves the tablet coating, exposing the hydrophobic acrylic matrix. After the film coating on the tablet has dissolved, GI fluid enters the tablet matrix release of oxycodone from OxyContin, resulting in the dissolution of the entrapped oxycodone and diffusion of oxycodone through the tablet matrix.

The water-insoluble matrix of the AcroContin delivery system renders the oxycodone release from the OxyContin tablets independent of surrounding pH [7]. Mandema et al. The resulting pharmacokinetic models were then used to predict mean concentration vs time profiles for dosing of OxyContin q12h and immediate-release oxycodone q6h for 3.

Unlike oxycodone immediate-release, the shape could not be accurately described mathematically using a single exponential term i.

However, the observed absorption profile for OxyContin could be accurately described mathematically as the sum of two exponential terms i. These proportions represent the mathematical factors that scale the contributions of the two exponential terms so that they sum to give the observed OxyContin absorption profile. Nor is there a specific relationship between the two retardants and the two terms in the absorption model.

At the start of oxycodone absorption, the rate of absorption for immediate-release oxycodone is more than eightfold higher than the rate for OxyContin.

The modeling indicates that absorption from a dose of an immediate-release oxycodone solution will be essentially complete approximately 1. Wallace et al. The elementary OROS osmotic pump delivery system consists of a tablet core of drug surrounded by a rate-controlling semi-permeable membrane coating that is pierced by a small 0.

The core table has two layers, one containing the drug the active layer and the other containing a polymeric osmotic agent the push layer , which operates on the principle of osmotic pressure. The semi-permeable membrane permits water to enter from the patient's stomach into the core tablet when the tablet is swallowed, thereby dissolving or suspending the drug. As pressure increases in the osmotic layer, it pumps the drug solution out of the delivery orifice at a constant rate of about one to two drops per hour.

Only the drug solution not the undissolved drug is capable of leaving through the small delivery orifice. The system is designed such that only a few drops of water are drawn into the tablet every hour. The rate of water inflow into the tablet as well as the release of drug solution from the tablet depends on an osmotic gradient between the contents of the two-layer core and the fluid in the GI tract.

The capsules were the first oral modified-release opioid product that contained hydromorphone HCl. The product used an around-the-clock matrix pellet formulation to achieve a biphasic release of drug that resulted in a relatively rapid rise to an initial peak concentration, followed by a second broad peak with therapeutic plasma concentrations maintained over the hour dosing interval [22].

During product development, results indicated that consuming ethanol while taking Palladone disrupted the modified-release mechanism of the product and resulted in the absorption of a potentially fatal dose of hydromorphone [21]. In July , the FDA advised Purdue that the risk of alcohol interaction cannot be adequately managed with warnings alone, and, at the request of the FDA, Purdue suspended all marketing and sales of Palladone [21].

After the withdrawal of Palladone from the market, the FDA recommended that makers of other ER formulations conduct investigations to determine the risk of alcohol-induced dose-dumping, whereby alcohol interacts with the ER characteristics to yield unintended, rapid drug release in a short period of time [24,25]. As a result, the Avinza label was revised to warn against consumption of alcohol and use of medications containing alcohol while taking the product [26,27].

Of interest was the high degree of variability of peak drug concentration C max during coadministration. On the basis of these data, the manufacturer cautions against coadministration of both formulations with ethanol [29,30]. The nature of the interaction of oxymorphone ER and alcohol is unknown.

In vitro dissolution studies suggest it is not caused by an ethanol-mediated deterioration of the formulation. Similar interactions have been seen with food suggesting that effects on gastric emptying or splanchnic blood flow may be contributing. Johnson et al. There were no serious adverse events or deaths reported during the study. The FDA has reviewed data from this study, has concurred that there is no interaction between Kadian and alcohol in vivo when administered concomitantly, and has not required any changes to the package insert [32].

Plasma samples taken predose and at regular intervals up to 48 hours after dosing were assayed for hydromorphone concentrations; a mixed-effect anova was done on log-transformed data [33]. Plasma hydromorphone concentrations were slightly higher after dosing with all alcohol treatments in both the fasted and fed subject groups. Median T max values were between 12 and 16 hours and ranges were similar for all treatments [33].

C max values increased after alcohol compared with no alcohol, with the increase slightly lower in the fed state. The greatest mean increase in C max observed was 1. Sathyan et al. The results indicate that the CR properties of this formulation are maintained in the presence of alcohol [33]. Purdue Pharma has conducted in vitro studies of the effect of alcohol on the dissolution profile of MSContin and OxyContin tablets.

These in vitro dissolution studies show that exposure to alcohol does not increase the rate at which morphine is released from MSContin tablets or at which oxycodone is released from OxyContin. Further, these in vitro dissolution studies demonstrate that the rate at which morphine is released from MSContin tablets or at which oxycodone is released from OxyContin tablets actually decreases as the concentration of alcohol is increased [7]. Therefore, Purdue Pharma has not conducted an in vivo study to assess the effect of alcohol on morphine release from MSContin tablets or OxyContin tablets in human subjects.

Other delivery system techniques e. The SABER delivery system is a biodegradable drug delivery platform that can be formulated for parenteral or enteral routes of administration, which appears to be especially well suited for small-molecule and protein delivery. After a single injection, an active agent may conceivably achieve a duration of action of up to 3 months small molecules or 30 days proteins. Opioids can currently be enterally administered in hourhour CR formulations.

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Am Fam Physician. Geneva, Switzerland: World Health Organization, Supernaw RB: Pain management: important principles in the drug management of pain. Hospital Physician. August ; Pain Med. McCarberg BH, Barkin RL: Long-acting opioids for chronic pain: pharmacotherapeutic opportunities to enhance compliance, quality of life, and analgesia. Am J Ther. New York: McGraw-Hill, J Pain Symptom Manage. West J Med. Clin Drug Invest. Abstract J Pain.