Archive for the ‘new pill formulation’ Category

FDA Approves Zubsolv, New Brand of Sublingual Buprenorphine

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Suboxone is getting competition from the generic preparations of buprenorphine/naloxone, and now another name-brand preparation has just been approved by the FDA.

It’s called Zubsolv, and the manufacturer, Orexo, says it takes less time to dissolve, is a smaller tablet, and tastes better. The company added a menthol taste. They also say their preparation has higher bioavailability, and the tablets come in two strengths: 5.7/1.4 buprenorphine to naloxone ratio, and 1.4/.36 ratio. The lower doses of buprenorphine per tablet are due to the higher bioavailability. Also, each tablet is contained in unit dose packaging, to reduce the risk of pediatric exposures.

Interestingly, the package insert says not to switch from one buprenorphine preparation to another, because other tablets have different amounts of buprenorphine than Zubsolv. That’s a problem for established patients. I’d like the manufacturer to give prescribers some information on how blood levels of their tablets compare to blood levels of other preparations of buprenorphine. I guess new patients could be started on Zubsolv.

On the company’s website, they claim that nine out of ten people prefer Zubsolv to Suboxone.

This medication should be available in pharmacies by September of this year.

I’m glad for every new buprenorphine product that’s released to the market, because I hope it brings the price down. Lower cost of medication means more opioid addicts could afford treatment.

I’m curious to see how this new preparation will be greeted by patients on buprenorphine.

New Drug, Old Problems?

The internet is abuzz with dire predictions surrounding the release of a more potent form of hydrocodone. Two drug companies have announced their intent to release a hydrocodone pill with a higher content of hydrocodone, with no acetaminophen. Currently, hydrocodone is available in doses of 5, 10, and 7.5mg per pill, combined with 325 or 500mg of acetaminophen (generic drug name of Tylenol). Teva Pharmaceuticals, based in Israel, has announced their intention to release a newer, higher potency form of hydrocodone that contains 45mg per pill.  If it’s approved by the FDA, it will contain over four times the opioid firepower in one pill that the next highest dose now on the market. Teva pharmaceutical is predicting up to $500 million in sales.

It’s a little early to start saying we’re going to have another OxyContin on our hands. Since 2009, the FDA demands each pharmaceutical company that manufactures powerful opioids have a plan in place, prior to the release of a new medication, to reduce the risk of harm to the public. This program is called “REMS” for “risk evaluation and mitigation strategy.” Before a higher strength hydrocodone can be released, the manufacturer must assure the FDA that all proper precautions are being taken to avoid excessive misuse and addiction.

We will never reduce medication misuse to zero, but we can learn from the past, and use available technologies to reduce the potential for drug misuse, to prevent another version of the OxyContin situation. Teva calls its product “TD” because it’s tamper deterrent, but I can’t find any information on which technology they plan to use. It will be a sustained-release preparation that is taken once every 12 hours.

Another company, Zogenics, is preparing to release Zohydro, their brand of higher dose version of hydrocodone. They say their version contains no tamper-resistant technologies.

Do we need another high potency, long-acting opioid for pain? And do we need it at a time in history when we’re on the crest of an opioid addiction epidemic? Some experts say yes, for a startling reason: We are seeing liver failure from acetaminophen overdoses.

According to one article, the most common cause of acute liver failure is acetaminophen, the generic name of the brand Tylenol. In 1998, liver failure from acetaminophen made up only 23% of the total number of liver failure cases, while in 2003, it rose to 51% of all acute liver failure cases. Of the people with unintentional acetaminophen overdoses, 63% were taking opioids containing acetaminophen, sometimes in combination with other medication that also contained acetaminophen. (1)

There’s not a wide margin of safety with acetaminophen.  The upper limit of what’s considered to be safe is about 3 grams per day of acetaminophen, but if the person has underlying hepatitis B or C, or damage from alcohol ingestion, not even 3grams is a “safe” dose. Some hydrocodone preparations now contain 500mg per tablet, so even at therapeutic doses that’s coming close to a toxic level of acetaminophen.

Opioid addicts often take much more hydrocodone than prescribed, regardless of the amount of acetaminophen. Addicts often take 15 or 20 pills of hydrocodone per day, which could be as much as 10grms of acetaminophen per day. And they take this day after day. An ordinary person might ask, “Why would anyone take the risk of damaging their liver like that?” But that’s addiction. Addiction is about loss of control. I’ve heard dozens of addicts entering treatment voice concerns they’ve damaged their livers because of pain pill use. They describe the curious predicament of taking pills because the addiction compels them to do so, all the while hoping they won’t die from liver failure. It’s a strong statement about the strength of addiction.

While acetaminophen-free hydrocodone may not trash your liver, it can still trash your life, if you become addicted.

  1. Larson AM et al, “Acetaminophen-induced Acute Liver Failure: Results of a U.S. Multicenter, Prospective Study,”  Hepatology, 2005;42:1364-1372.

New Opioids

I’ve blogged about states that have passed new laws addressing the prescribing of opioids, but the manufacturers of prescription opioids medications also have made changes to help reduce the potential for medication misuse. Of course, opioids will never be misuse-proof, but at least it’s a little harder to misuse some of the newer ones.

Oxecta is a new immediate-release brand of the drug oxycodone. It’s formulated so that it breaks into chunks when crushed, instead of a powder. When it’s mixed with water, it forms a gel so that it can’t be injected. This pill contains sodium laurel sulfate, a substance that irritates the nose if snorted.

Lazanda is a new delivery form of a very potent opioid, fentanyl. This brand is designed to be used as a nasal spray, which I would expect to be very addictive. The preparation itself has no anti-abuse features, but in order to distribute, dispense, prescribe, or be prescribed this medication, parties have to sign an agreement and be enrolled with the drug company. This extra scrutiny is hoped to deter diversion by distributor, pharmacy, doctor, or patient. Physicians must take a training program specific for this brand, and be enrolled with the drug company as a prescriber, or pharmacies can’t dispense to the patient.

Patients also need to complete a patient-prescriber agreement. Many people (like me) think doctors aren’t likely to jump through these extra hoops to prescribe this particular brand, when other brands of the same medication are already on the market, though not in the form of nasal spray.

Remoxy, another brand of oxycodone, hasn’t yet been FDA approved. Supposedly, it’s resistant to injection or snorting, and also has been formulated to be resistant to alcohol extraction.

Drug companies are now required by the FDA to have plans to evaluate and mitigate the risks associated with the opioid drugs they manufacture, particularly if they make sustained release or long-acting opioid preparations. This cooperation by drug manufacturers is a necessary part of turning the tide of opioid addiction in this country.

Last year, Purdue Pharma re-formulated OxyContin, making it more difficult to crush to snort or inject.  I noticed a sudden drop-off in patients entering treatment for pain pill addiction who said OxyContin was their drug of choice. During the years 2002 through 2007, nearly all of the opioid addicts I admitted to treatment said OxyContin was their preferred drug. It became obvious that the re-formulation made a big difference.

Addicts can and will still abuse these medications orally to get high, but the new formulations really do reduce abuse by making pills less likely to be snorted or injected.

The New OxyContin Formulation

Over the last three weeks, at least five of the opioid addicts I’ve admitted to treatment said they wanted help because they couldn’t abuse the new form of OxyContin.

 And I say: Hallelujah! It’s about time!!

 This new tablet, approved by the FDA in April of this year, appeared recently on the black markets of this area, replacing the older, more easily abused OxyContin. The new tablet is bioequivalent to the older tablet, meaning the same amount of oxycodone, the active ingredient, is available to the body when swallowed whole, as it’s meant to be. In other words, the same amount of pain reliever is given to the body. However, it’s more difficult to crush for the purpose of snorting or injecting, because it turns into a gummy ball.

Purdue Pharma, the drug company that makes OxyContin, admits this new formulation isn’t abuse-proof, but hopes it will be more resistant to abuse.

The patients I’ve talked to say the new tablet is a big disappointment. One patient, who usually chews her pill to get a faster high, said it was like trying to chew a jelly bean. Other patients said they could crush the tablet, but got a kind of gelatinous mess that was impossible to snort or inject.

 For pain relief, the opioid in OxyContin lasts much longer when it’s taken as directed and swallowed whole. Addicts prefer to crush and snort or inject because of the quick high they feel with this route of administration. But when used in this way, it leaves the body faster, and the addict usually needs to find more opioid within six to eight hours to avoid withdrawal.

Before I applaud Purdue Pharma for this change, my cynical mind asks a few questions: Why didn’t the company make this change earlier?

In 2002, a Purdue Pharma representative testified before congress, saying that the company was working on a re-formulation of OxyContin, to make it harder to use intravenously. This representative said they expected to have the re-formulated pill on the market within a few years. (1)  But it took eight more years.

Sterling, the drug company that makes Talwin, another opioid pain medication, was able to re-formulate their drug within a few years when they discovered it was being abused frequently. This was in the 1980s, when, presumably, medication technology wasn’t as advanced as today. Sterling added naloxone, an opioid blocker that’s inactive when taken by mouth, but puts an addict into withdrawal when it’s crushed and injected. It worked great. Talwin isn’t a commonly abused drug.

 I’m assuming that Purdue Pharma holds the patent for this new formulation that makes their tablet gummy when crushed. Purdue probably teaches its sales staff to market the new OxyContin as a safer option than older versions, perhaps available in cheaper generics. So did they wait to re-formulate until their patent was ready to expire? I don’t know, but time will tell.

At any rate, this drug is now just a little bit safer, for now. People with addictions are often clever and creative. I won’t be surprised if soon there’s a way to defeat this new technology.

Just think what addicted people could do, if they directed their talent and intelligence in ways that would help and not hurt them. There would be no stopping them.

1. United States Senate. Congressional hearing of the Committee on Health, Education, Labor, and Pensions, on Examining the Effects of the Painkiller OxyContin, 107th Congress, Second Session, February, 2002.

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