Shortage of prednisone tablets

The American Society of Health-System Pharmacists reports a shortage of prednisone tablets. I think this shortage bulletin may be a correction for the prednisolone shortage bulletin, which has now disappeared from the ASHP website. See my earlier post, Shortage of prednisolone tablets, for an explanation of what was apparently an error.

There are five manufacturers of prednisone tablets listed in the most recent bulletin. Two give a raw material shortage as the reason for their shortage, but don't indicate whether it is the prednisone itself or a tablet excipient that is in short supply. Three manufacturers don't give a reason for their shortage.

Shortage of injectable tromethamine

The American Society of Health-Care Pharmacists reports a shortage of injectable tromethamine. Hospira, the sole US-approved manufacturer, cites unspecificed manufacturing delays as the reason for the shortage. The blood becomes too acid because of the acid-citrate-dextrose anticoagulant used during cardiac bypass surgery. THAM, aka tromethamine, is used to make it less acid before restoring normal circulation. When someone goes into cardiac arrest, their blood almost always becomes too acid, and tromethamine is used in this instance as well.

Shortage of injectable dobutamine

The American Society of Health-System Pharmacists reports a shortage of injectable dobutamine. This drug increases the force with which the heart muscle contracts, making it possible for the heart to pump more blood without having to increase the rate at which it contracts. In other words, your pulse stays the same. WARNING: This is true for about 90% of the people given dobutamine. The other 10% may have both increased heart rate and blood pressure. Since dobutamine works on beta-receptors in the muscle, it is ineffective if you have recently taken a beta-blocker.

This is yet another shortage caused by Ben Venue's voluntary closure of its manufacturing facility, where it manufactured this drug on contract for Bedford Laboratories. There are two remaining manufacturers - Hospira cites unspecified manufacturing delays and Baxter does not give a reason for its shortage.

Dobutamine is used after heart surgery to help the heart recover, and is also given to people with heart failure to help keep blood flowing as well as possible.

Shortage of prednisolone tablets

The American Society of Health-System Pharmacists reports a shortage of prednisolone tablets. If you look at the link, however, only prednisone tablets are listed. They are not the same, the liver converts prednisone into prednisolone, which is the active form. If someone has a liver disease or insufficiency, they are given prednisolone for this reason.

Whichever is actually in short supply, there are now related shortages of hydrocortisone sodium succinate for injection, methylprednisolone acetate for injection, and dexamethasone sodium phosphate

Shortage of injectable sargramostim

The American Society of Health-System Pharmacists reports a shortage of injectable sargramostim. This drug shortage affects people whose white blood cells have been reduced during cancer chemotherapy, or eliminated entirely during a bone marrow transplant. There is a human protein that stimulates the production of white blood cells, and sargramostim is a synthetic version. As a class these drugs are known as immunostimulators, in this case a granulocyte-macrophage colony stimulating factor (GM-CSF). The brand name of the drug is Leukine, and Genzyme does not give a reason for the shortage. It is easy to speculate that the shortage is related to the fact that Sanofi-Aventis will acquire the drug from Genzyme effective July 1, 2012. The Chemocare website has a more complete description of this drug.

Shortage of injectable succinylcholine chloride

The American Society of Health-System Pharmacists reports a shortage of injectable succinylcholine chloride. The "Implications for Patient Care" make clear that serious errors may arise when substituting blocking agents due to this shortage. Anesthesiologists typically use this drug to relax the skeletal muscles to facilitate intubation, mechanical ventilation, and the surgical procedure itself. The drug may be administered once for short surgical procedures or multiple times for longer operations. The fact that the body breaks the drug down so quickly is a matter of safety for the patient and convenience for the surgical team. A longer-acting blocking agent will preferably be used for longer operations during the shortage, but then unfamiliarity with less commonly used drugs and their antidotes can lead to problems.

Shortage of injectable hydrocortisone sodium succinate

The American Society of Health-System Pharmacists reports a shortage of injectable hydrocortisone sodium succinate. When your body's immune response is killing you or causing you suffering, this injectable steroid will sometimes save your life or alleviate symptoms while another treatment is started. In the case of a life-threatening allergic reaction (anaphylactic shock), it will help you survive. It will also help you through the acute phase of a disease such as ulcerative colitis until a longer-term treatment can take effect. Here is Hospira's drug information sheet. I recommend reading the many uses for this drug. This shortage has probably arisen as a sequel to the Shortage of injectable methylprednisolone acetate.

I find it interesting that Hospira cites lack of manufacturing capacity for their shortage. This is the first time I have noticed something more specific than "manufacturing delays." One thing to keep in mind is that lack of manufacturing capacity can mean that the production line is being used for some other product. The questions are, what product is being manufactured instead, and why? Is the shortage due to negotiations with a contract production company? The answers to these questions are usually unavailable to the public. Manufacturing capacity is also lost when all or part of a facility is shut down because of violations of Good Manufacturing Practices. Pfizer does not give a reason for the shortage of their brand name version, Solu-Cortef.

Missouri Adopts Propofol for Execution by Lethal Injection

As of May 15th, Missouri has adopted this protocol for execution by lethal injection using propofol. (Note the misspelling of the brand name Diprivan.) APP manufactures both Diprivan and generic propofol, Hospira only the generic. The American Society for Health-System Pharmacists reports that the drug is in short supply due to "manufacturing delays" at Hospira.

Given the new protocol, the Missouri Attorney General has petitioned the Missouri Supreme Court to set execution dates for the nine death row inmates who do not already have a date set. All prisoners and their attorneys were also informed, and legal challenges to the untested execution protocol are to be expected.

I tell the detailed story of lethal drugs for injection in my posts below, but here is a summary. Hospira was the only US-approved source of the sodium thiopental that was originally used for lethal injection, but the Italian manufacturing facility with which they contracted refused to produce the drug without guarantees that their output would not be used for executions. Hospira's company policy does not prevent the sale of their products for this purpose. Nebraska fraudulently obtained thiopental from the Indian manufacturer Naari under the guise of having drug samples shipped to Zambia for approval and registration in that country. Naari has requested that the Nebraska Supreme Court order the return of their product, to no avail. After thiopental became hard to obtain, pentobarbital began to be used. It is now unavailable from Lundbeck, the only US-approved supplier, due to the company's enforcement of a shipping procedure designed to prevent the sale of their product for executions. Texas obtained some of their product by deceit, using a DEA registration number for the long-shuttered Huntsville Prison Hospital, and refused to return it to the manufacturer. Texas Attorney General Greg Abbott recently upheld an open records request that revealed that the state has supplies for 23 executions because the Texas Department of Criminal Justice is not following its own protocol and mixing a backup dose. (See syringes 1A, 2A, 3A, and 4A in the Missouri protocol for an example of how backup doses are prepared.)

Shortage of injectable pentobarbital for execution by lethal injection

Shortage of injectable pancuronium

Shortages of Drugs for Lethal Injection

Shortage of injectable potassium chloride

Shortage of sodium thiopental for lethal injection

Nebraska's thiopental for lethal injection

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 DTaP vaccine

The American Society of Health-System Pharmacists reports a shortage of diptheria, tetanus toxoid, and acellular pertussis vaccine. Daptacel is the brand name of this Sanofi-Pasteur vaccine. Please see my related post earlier today and the CDC guidance document.

Shortage of DTaP - IPV/Hib vaccine

Guidance for Vaccinating Children during the 2012 Pentacel® and Daptacel® Shortage

Sanofi-Pasteur cites "manufacturing delays" for the Daptacel and Pentacel shortages. Here are some related blog posts, but of course the mainstream media might also be a driving force behind this shortage as people read and react to the risk of not vaccinating their children at all or not completing the recommended childhood vaccination schedule.

Washington State Declares Whooping Cough Epidemic
Idaho infant dies from whooping cough amid regional outbreak
Washington state on track for major pertussis epidemic
Whooping Cough Epidemic

The blogs and this New York Times article make several key points: (1) Most cases since before a vaccine was available. (2) Until last year, Washington state had the easiest law allowing parents to opt out of immunizations required by public schools for fear of vaccines, philosophical, or religious reasons. (3) Washington state had the highest opt out rate. (4) The rest of the population is put at increased risk if 5-15% of the population is unvaccinated. (5) Changes in the vaccine to reduce side effects have resulted in a shorter period of protection against the disease (Physicians First Watch).

Shortage of DTaP - IPV/Hib vaccine

The American Society of Health-System Pharmacists reports a shortage of diphtheria, tetanus toxoid, acellular pertussis and inactivated poliovirus/haemophilus B conjugate vaccine. The brand name for this vaccine is Pentacel. Sanofi-Pasteur will only take orders from previous purchasers based on the Center for Disease Control's recommendation that vaccinations begun with one manufacturer's product continue using the same manufacturer's products. If changes are required, please refer to Guidance for Vaccinating Children during the 2012 Pentacel® and Daptacel® Shortage. Sample schedules for birth through six years of age are included. The Daptacel (DTaP) shortage will be the subject of my next post.

Shortage of injectable methocarbamol

The American Society of Health-System Pharmacists reports a shortage of injectable methocarbamol. The only US-approved version is sold under the brand name Robaxin, although there are other brand names for combinations with aspirin, acetominophen, and ibuprofen. West-Ward gives no reason for the shortage. This drug is a muscle relaxant which acts at the level of the nervous system to block pain signals sent to the brain. Methocarbamol is much less addictive than other muscle relaxants, but it does have a sedative effect and may cause dizziness. It is one of many drugs that the National Committee for Quality Assurance considers high-risk in the elderly.

Shortage of tolmetin sodium

The American Society of Health-System Pharmacists reports a shortage of tolmetin sodium. This drug is used to relieve the symptoms of adult and juvenile rheumatoid arthritis and also osteoarthritis over the short term. There are significant possible side effects, so the lowest dose for the shortest time is desirable. Short-term pain relief is probably its best use, and alternatives should be sought for long-term treatment of these chronic inflammatory conditions.

Shortage of injectable sodium lactate

The American Society of Health-System Pharmacists reports a shortage of injectable sodium lactate. If your blood gets too acid, bad things are going to happen to you. Your doctor may choose to inject you intravenously with an appropriate amount of diluted sodium lactate to solve the problem. The body's normal metabolism converts the lactate to bicarbonate, which will neutralize acid in the blood.

Shortage of esomeprazole magnesium oral suspension

The American Society of Health-System Pharmacists reports a shortage of esomeprazole magnesium oral suspension. This drug shortage affects people who have been prescribed the oral suspension for various reasons. There is no shortage of the capsules containing the same drug. AstraZeneca cites "manufacturing delays" for the shortage of their brand name drug, Nexium. If someone is taking aspirin (but not the 81 mg enteric-coated aspirin), ibuprofen, naproxen or various other non-steroidal anti-inflammatory drugs over the long term, Nexium is useful to avoid the ulcers which are a common adverse reaction to these drugs. A person suffering from gastroesophageal reflux disease may take Nexium to prevent damage to their esophagus when their stomach contents come back up the wrong way. Since even very young children may have GERD, this is probably the main group that will be affected by this drug shortage. Nexium is also taken with amoxicillin and clarithromycin to eradicate Helicobacter pylori and thus avoid the recurrence of ulcers due to this infection.

Their are important drug interactions with some other commonly prescribed drugs and also with anti-HIV drugs, so it is important that your doctor know what you are taking, both prescriptions and over-the-counter drugs.

Shortage of live intravesical BCG vaccine

The American Society of Health-System Pharmacists reports a shortage of live intravesical BCG vaccine. This vaccine contains live but weakened tuberculosis bacteria. It is injected into carcinomas of the urinary bladder, hence the name intravesical. It is also approved for early stage papillary tumors that recur after surgery. The exact mechanism of action of the vaccine is unknown, but presumably the body's immune system reacts strongly to wall off the injected bacteria into a benign lump called a granuloma and in the process develops antibodies that also kill the tumor cells.

Shortage of desmopressin rhinal tubes

The American Society of Health-System Pharmacists reports a shortage of desmopressin rhinal tubes. Rhinal tubes are used to blow desmopressin far up into the nasal cavity. Desmopressin is a synthetic version of the pituitary hormone vasopressin. Very rarely individuals cannot produce this hormone for genetic reasons and thus produce large volumes of urine. This condition is known as central diabetes insipidus (aka cranial or neurogenic DI). The rhinal tubes are typically for children or anyone who cannot take the oral medication. An adult may blow the medication up the nose of a child. Here is a picture of the tube in action after it has been filled with a prescribed amount of the drug from a small bottle. 

Shortage of injectable secretin

The American Society of Health-System Pharmacists reports a shortage of injectable secretin. ChiRhoClin, Inc., does not give a reason for the shortage for their brand name injectable synthetic human secretin, ChiRhoStim. When the stomach has finished working on the food you eat, a valve opens and its contents move into the first part of the small intestine, the duodenum. When the acid stomach contents hit the wall of the duodenum, specialized cells release secretin. The secretin causes the pancreas to dump its digestive enzymes into the duodenum along with a lot of bicarbonate to neutralize the acidity. Secretin also inhibits the production of another hormone called gastrin that makes the stomach produce acid.

ChiRhoStim is injected to check whether the pancreas is functioning normally. If a device called an endoscope is inserted into the duodenum, visual confirmation that the pancreas is emptying into the duodenum can be obtained. The endoscope is also a way of locating the Ampulla of Vater, the opening into the duodenum from the pancreas.

A third use for ChiRhoStim is diagnosing tumors called gastrinomas. Instead of inhibiting gastrin production like it does with a normal stomach, secretin causes gastrinomas to secrete gastrin, which can then be detected.

Shortage of dantrolene capsules

The American Society of Health-System Pharmacists reports a shortage of dantrolene capsules. This drug relaxes the muscles and is especially useful to people with spinal cord injuries, strokes, cerebral palsy and multiple sclerosis. Muscle spasms, pain and stiffness are reduced. The drug is started at a low dose and increased until the muscle symptoms improve or adverse reactions to the drug outweigh its benefits. For example, sometimes dantrolene relaxes your muscles to the point where you can't swallow correctly. The drug can occasionally cause serious and even fatal liver problems, but blood tests for liver enzymes are used to give warning of this problem, which usually occurs at doses over 400-800 mg/day.

Doc, Where Were You During Human Physiology Class?

Folinic Acid and 5-Fluorouracil, the Cancer Drug Shortage That Isn't.

Folinic acid is routinely used in cancer chemotherapy regimens that also use 5-fluorouracil. At Medscape Today, Dr. John Marshall explains how he responds to doctors and patients who ask him how to manage a shortage of folinic acid, aka leucovorin. Although the article is titled Drug Crisis: Getting by Without Leucovorin, the article's content makes clear that there is no crisis. You can read the article by registering with Medscape, but here is a key quote.

If you really want to give leucovorin you could, in fact, just give folic acid. You could go to the drugstore, and for not very much money get some folic acid and have the patient take it throughout the duration of the leucovorin shortage.

An additional factor is that folic acid is very inexpensive compared to leucovorin. Some physicians are substituting an even more expensive brand name drug, Fusilev (levoleucovorin), that contains only the purified active form of leucovorin. The point is that the human body changes folic acid, leucovorin, and Fusilev into the same tetrahydrofolate which increases the effectiveness of the 5-fluorouracil.

Methotrexate Rescue

On the other hand, leucovorin and levoleucovorin are important to a cancer chemotherapy regimen that uses high-dose methotrexate. When there is a shortage of either, the two compounds are best used for this purpose because they save the body from the toxic effects of the high doses of methotrexate that can be an effective cancer treatment. Carefully timed doses must be given intravenously for this system to work.

Off-Label Use for Methotrexate Overdose

A common off-label use of leucovorin and levoleucovorin is to save the patient from the ill effects of a methotrexate overdose.

As reported by the American Society for Health-System Pharmacists, there is a current shortage of leucovorin, but Fusilev is available. The leucovorin shortage is yet another caused by the voluntary shutdown of the Ben Venue plant where the drug was manufactured under contract with Bedford Labs.