Shortage of injectable methylprednisolone acetate

The American Society of Health-System Pharmacists reports a shortage of injectable methylprednisolone acetate. This steroid medication is used to decrease the body's immune response as necessary. It may be directly injected into joints affected to arthritis, for example. It uses are so widespread that I recommend reading them yourself in the information sheet for Pfizer's brand name version, Depo-Medrol. Neither Pfizer nor the two generic drug companies give a reason for this shortage.

Shortage of nefazodone tablets

The American Society of Health-System Pharmacists reports a shortage of nefazodone tablets. Teva did not provide a reason for this drug shortage. My guess is that this drug is going to be discontinued because of poor sales. The drug was discontinued in some countries because it rarely causes hepatotoxicity to the point where a liver transplant is required. There are also many drugs that interact with nefazodone to the detriment of the patient. That said, it is rather unique in that it is an antidepressant which inhibits the reuptake of serotonin, norepinephrine, and dopamine and has a low incidence of negative effects on libido. In general, the drug is not a first or even second choice among the many antidepressants now available.

Shortage of cyclosporine (modified) oral presentations

The American Society of Health-System Pharmacists reports a shortage of cyclosporine (modified) oral presentations. Chemically modified cyclosporine immediately forms an emulsion in water, making it more available to the body. It is more likely to be used to treat psoriasis and rheumatoid arthritis, while unmodified cyclosporine is more likely to be used to prevent rejection of kidney, heart, or liver transplants. Sandoz cites unspecified manufacturing delays as the cause of their shortage. Teva and Watson give no reason for their shortage.

The Life Cycle of a Drug: Effexor XR

Pfizer's wholly-owned Wyeth subsidiary owned the original compound patent for venlafaxine hydrochloride (Effexor XR). This patent expired in 2008, but the company had filed a series of patents as explained in my post, Proprietary Drug Patents. with the aim of extending their patent monopoly to 2017. In 2002, Teva was the first generic manufacturer to file an abbreviated new drug application for the equivalence of their extended-release venlafaxine hydrochloride to the brand name product. In 2005, Wyeth entered into a pay-for-delay agreement with Teva to delay marketing of their generic until 2010. Among other things, Wyeth agreed to delay marketing an authorized generic until Teva's marketing exclusivity period for its generic ended. As is typical, this settled all the litigation between Wyeth and Teva. Wyeth also agreed to resolve any later litigation about the unenforceability or noninfringement of its follow-up series of drug development patents.

The above description is typical in the US. What is atypical is that a complaint in federal court alleging fraud by Wyeth and Teva has since been filed. Thanks to Don't trade out lives away for posting on this subject with links to the complaint and Reuters' announcement of the suit. The Incidental Economist's Kevin Outterson also has a post with links to the Federal Trade Commission's report on the consumer cost of pay-for-delay deals and an academic paper on the subject. Pfizer and Wyeth emphasize that they have engaged in a typical process that is lawful in the US. Perhaps the process is about to change?

Drug War?

The National Community Pharmacists Association surveyed 675 independent pharmacists. Their main concern was the shortage of Adderall XR (amphetamine mixed salts) and its generic equivalents, prescribed for attention-deficit hyperactivity disorder. As for drug shortages overall, some key results were:

• "96 percent of responding pharmacists experienced a drug shortage in the past six months.
• 82 percent have been experiencing drug shortages at least daily (59 percent) or weekly (23 percent).
• 80 percent said that the average shortage last [sic] three weeks or longer.
• 78 percent indicated that patients have to go without taking their medication(s) due to shortages, suggesting that patients are unable to obtain their needed supply from alternative pharmacies, either."

Amphetamine, amphetamine mixed salts, dextroamphetamine, and (rarely) methamphetamine are all approved ADHD treatments, and alleviate the symptoms in 70-80% of children. An excellent summary of the disease itself and the simultaneous treatments required is provided by the National Resource Center on ADHD. The disease may continue on into adulthood or the initial diagnosis may occur in adults.

As part of the War on Drugs, the Drug Enforcement Administration sets production quotas for these drugs. Note in my post last fall that the shortage of amphetamine mixed salts for immediate release reported in the ASHP bulletin was in part due to the fact that Teva had produced the quantity allowed by the DEA quota restrictions. The immediate release form is the only one approved for treatment of children 3-6 years of age. The FDA has asked the DEA to increase quotas to solve the problem, but the DEA maintains that its quotas are adequate to meet the demand and that the shortage is due to drug manufacturers (Shire in the case of Adderall XR) choosing to produce and sell the more expensive and more profitable brand name version of the drug. For example, since Shire supplies Teva with the active pharmaceutical ingredient, the more of the API that Shire uses to produce Adderall XR, the less there is for Teva to produce the generic immediate release formulation.

The three-sided dispute between the FDA, DEA and drug manufacturers has led to an investigation by US Congressional Representatives Henry Waxman, Diana DeGette, Frank Pallone, and Chris Van Hollen. More information about the investigation may be found in this post by Ed Silverman at Pharmalot. The Executive Branch has issued Executive Order 13588 -- Reducing Prescription Drug Shortages addressing actions that can be taken by the FDA, Department of Justice, and drug manufacturers. For example, Shire discontinued Adderall IR [immediate release], and supplies Teva with the API to produce the generic equivalent. Under the executive order, a discontinuation such as this would now require six months notice. Representative DeGette and Senator Amy Klobuchar introduced House and Senate companion bills (HR 2245/S 296) last summer to address drug shortages, and DeGette was interviewed on that topic by Sarah Kliff of the Washington Post. The American Society of Health-System Pharmacists has a legislative summary of these bills (PDF), which I believe remain pending in committee. Comments and updates on the bills' status will be welcome.

Shortage of naltrexone tablets

The American Society of Health-System Pharmacists reports a shortage of naltrexone tablets. This drug shortage is likely due to a shortage of the active principal ingredient, naltrexone hydrochloride. Covidien states that this is the reason they have the drug on back order, but Teva and Sandoz did not give a reason. This drug is used to combat alcohol and opioid drug addiction by combining with the receptors in the brain that are occupied by alcohol and opiates.

A question that arises is whether this shortage might be due, at least in part, to FDA approval of 50 mg tablets. Addicts seem to find this amount too high, and ask physicians for prescriptions from compounding pharmacies at a lower dose. Could that be how the active ingredient is being used instead of for the 50 mg tablets? Other addicts take the dubious route detailed on the Internet of obtaining a prescription for the 50 mg tablets, putting a tablet into suspension in distilled water, and gradually increasing their daily intake to combat their withdrawal symptoms.

Shortage of nystatin vaginal tablets

The American Society of Health-System Pharmacists reports a shortage of nystatin vaginal tablets. Teva, the sole manufacturer of these tablets approved for use in the US, could not give a reason for this shortage. Since there is also a shortage of the oral suspension of nystatin dating to last November 8th, it may be that the problem is a shortage of the nystatin itself. If a simple microscopic exam confirms a vaginal yeast infection, these tablets are one of the main presentations prescribed.

Shortage of lansoprazole orally disintegrating tablets

The American Society of Health-System Pharmacists reports a shortage of lansoprazole orally disintegrating tablets. This particular presentation of lansoprazole is very important for the treatment of gastroesophageal reflux disease, commonly called heartburn, but uncommonly serious in some people whose esophagus is constantly exposed to stomach acid. This results in burns, ulcers and swallowing difficulties. The significant fact is that this drug formulation disintegrates in the mouth and can be taken without swallowing water. The shortage is caused in part by the voluntary withdrawal from the market of Teva's product earlier this year. The FDA notice explains in detail. Sandoz provided no reason for their shortage.

Shortage of Tetracycline Capsules

The American Society of Health-System Pharmacists reports a shortage of tetracycline hydrochloride capsules from Teva Pharmaceuticals and Watson Pharma. The current FDA-approved information regarding this drug is provided on the Watson website. (UPDATED LINK) Perhaps you have been discouraged from reading documents like this by the small print or the technical nature of the information provided. Your doctor can help with the latter, but I am taking this opportunity to point out that enlarging the text to 200% or greater in a PDF reader is a big help for readability. You could do this on a copier as well.

Since I routinely look for this kind of information on-line as part of my business activities, one of the first things I do is go to the end of the document and see when it was produced. In this case you can see that it was last revised in July 2011. Prominently displayed above the date is where the drug is manufactured (India) and where it is distributed (US). This information can be useful if you have heard of manufacturing problems at a particular location, or want to find out whether there are any.

There are probably quite a few people who are aware that tetracycline can discolor your teeth, and detailed information about that can be found under CONTRAINDICATIONS, p. 1, column 2, paragraphs 2 and 3. The first line in this section contains useful information, but is also an example of how the information presented is not so straightforward. The tetracyclines are a group of antibiotics, of which tetracycline is the founding member. If you are hypersensitive, i.e., allergic, to one member of the group, you are going to be hypersensitive to all of them. I hasten to add that this is not true of all drug groupings, so you can't generalize.

Now look further up the same column at INDICATIONS AND USAGE. In previous posts I explained what an indication is in the medical sense of the word, and explained off-label use. In this section of the document you will find the list of what the FDA considers valid reasons to use tetracycline hydrochloride capsules. Any other use is an off-label use, by definition. Please recall from my previous post that there are sometimes good reasons for off-label use of a drug.

Still in INDICATIONS AND USAGE, the first line, notice the words "susceptible strains" and the subheading Susceptibility Testing at the top of the column, where there is a technical explanation of how a susceptible strain is defined in this case. There have been many reports of antibiotic-resistant strains in the media, and there are many that are resistant to tetracycline. So many, in fact, that I personally would not take this drug unless the prescribing doctor was first willing to send a sample of whatever was infecting me to the lab for an antibiotic-sensitivity test. (Antibiotic susceptibility and sensitivity are the same thing.) If you read on through the CONTRAINDICATIONS section, you can see that there are valid reasons not to take this antibiotic, and you are going to need professional help in order to know whether any apply to you.