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 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 50% dextrose for injection

The American Society of Health-System Pharmacists reports a shortage of 50% dextrose for injection. Hospira gives no reason for the shortage beyond "manufacturing delays." If a person is in insulin shock, injection of this concentrated dextrose solution is key to their recovery to normal blood sugar levels. Secondly, if a person cannot take food by mouth, or food intake is inadequate for some reason, 50% dextrose is an important supplement. Third, if someone suffers from edema and/or is having circulatory problems, the dextrose concentrate delivers a lot of calories without loading their system down with a lot of water as well.

Shortage of injectable meperidine

The American Society of Health-System Pharmacists reports a shortage of injectable meperidine. Hospira cites increased demand and manufacturing delays as the reasons for the shortage of their brand name product, Demerol. West-Ward produces the generic product, but no pre-loaded syringes. I was given Demerol in the mid-seventies by a dental surgeon, and my only experience with painkillers since then has been for dental procedures. I have never since been given Demerol (meperidine hydrochloride). I am curious to know of other people's experience. Has this drug been administered to you before and/or after surgery? at childbirth? for chronic pain such as fibromyalgia?

This is an opioid narcotic analgesic for moderate to severe pain and was at one time the drug of choice for addicted doctors and nurses. Is that still the case, or is that decades-old news?

Shortage of injectable enalaprilat

The American Society of Health-System Pharmacists reports a shortage of injectable enalaprilat. This drug shortage is yet another that arises from the voluntary closure of Ben Venue's manufacturing facility, where injectable enalaprilat was produced under contract for Bedford Laboratories. There is no mention of why Hospira's product is in short supply. This drug will injure and possibly kill a developing fetus. When medication cannot be taken by mouth, this is an injectable option for control of high blood pressure. It is an angiotension I-converting-enzyme inhibitor (ACEI).

Shortages of Drugs for Lethal Injection

Shortage of injectable pancuronium: Pancuronium is the second of  three drugs injected during an execution by lethal injection in Texas. The only US-approved supplier is Hospira, which cites manufacturing delays as the reason why new supplies of the drug will not be available until April 2012. See my previous post, Shortage of injectable pancuronium. Last month Lancet published an open letter from  Dr. David J. Nicholl and 24 other physicians to Michael Ball, Hospira's CEO, and his response was published in the same issue. The physicians asked the company to make changes in its distribution of the drug to prevent it being used for executions. The company's response was that it has publicly opposed the use of its drugs for lethal injection, that restricting distribution might affect the availability of pancuronium to patients who needed it, and that the physicians' concerns were best addressed to governments, legislators and regulatory bodies. The Guardian reports on restrictions put in place by the European Commission. 

Shortage of injectable thiopental and the US response; Purchases from Dream Pharma, West London:  Hospira was also the sole US supplier of thiopental, formerly the first drug injected during an execution by lethal injection in Texas. It discontinued this drug because the manufacturing facility in Italy refused to produce the drug without guarantees that it would not be used for executions. As thiopental stocks diminished in 2010 and 2011, At least ten US states (PDF, p. 8) purchased thiopental from middleman Matt Alavi, a businessman with a one-man West London company, Dream Pharma, located behind a driving academy. The vials were shipped FedEx under unapproved and illegal environmental and regulatory conditions. When Brandon Rhode was executed with this drug, his eyes remained open, meaning that the anesthetic didn't work and that he was almost certainly suffering from suffocation because the pancuronium injection paralyzes the muscles. He would also have experienced burning pain throughout his body from the injection of the third component for lethal injection, potassium chloride, which stops the heart. He would have been unable to express this pain because of the pancuronium-induced paralysis. Emmanuel Hammond was grimacing with pain during his execution and his eyes first closed and then fluttered open according to Attorney Sheri Johnson. Attorney Dale Baich gave the British High Court a sworn statement that Jeffrey Landrigan’s eyes remained open during the lethal injection process. Through the efforts of various rights organizations this thiopental was surrendered to the appropriate drug agencies or seized by the DEA for unlicensed importation and distribution of a controlled substance. The most publicized seizures were the thiopental purchased by the state of Georgia and CorrectHealth, a company which has the Georgia state contract for medical care in its correctional system, from Dream Pharma. Dr. Carlo Anthony Musso, the owner of CorrectHealth, sold his thiopental to Kentucky and Tennessee, violating more controlled-substance laws. After a complaint from the Southern Center for Human Rights, the DEA seized the thiopental from all three states. The SCHR then petitioned the Georgia Composite Medical Board for revocation of Dr. Musso's medical license, which would end his supervision of executions in Georgia. 

US government requests importation from Germany: Also in 2011, US Commerce Secretary Gary Locke requested importation of thiopental from Germany.  Der Spiegel reported that his counterpart, German Vice Chancellor Philipp Rösler, declined. Thus the US has been cut off from legal importation of drugs for lethal injection from the European Union. 

Purchases from India: In 2010 and 2011 various US states inquired about and some purchased thiopental from India.  The Sunday Guardian reports that Navneet Verma, managing director of Kayem Pharmaceuticals, bought vials of thiopental with English labels from Mumbai company Neon Laboratories for sale to Nebraska and South Dakota because his existing stock was labeled in Portuguese for use in Angola. The Times of India reports that Kayem consists of a Mumbai office and storeroom, with a kitchen on a balcony. This seems very similar to the questionable situation with Dream Pharma. Later in 2011, Mr. Verma reversed his decision to sell more thiopental to various US states that had sent him inquiries.

Another Indian company, Naari, was duped by an Indian purchaser, Chris Harris, who stated that he was buying samples to ship to Zambia for approval and importation to that country. Instead, the drugs were sent to Nebraska, and Naari has protested to the Chief Justice of the Nebraska Supreme Court and started legal proceedings for their return. The Indian Express reported other details of this story. 

Shortage of injectable pentobarbital: Texas and other states reacted to the thiopental shortage by changing the first drug to pentobarbital. See my previous posts, Shortage of injectable pentobarbital for execution by lethal injection, update 1, and update 2.When asked for an opinion last year, Texas Attorney General Greg Abbott told the Texas Department of Criminal Justice that the information about stocks of injectable pentobarbital for execution is a public record  The TDJC later stopped releasing this information based on a Texas Supreme Court ruling that security concerns may sometimes trump the open records law, and has asked the AG for an opinion on a new open records request. Based on the previous request, Maya Foya, an investigator for the London-based human rights organization Reprieve, estimates that TDJC has 27 vials of pentobarbital. The Hunstville Item reports TDJC's response that it has a supply sufficient for the executions scheduled in 2012. As noted earlier, the vials have a two year expiration date, making present prison stocks unavailable for executions after 2013.

Last year a letter to US Attorney General Eric Holder revealed that Texas purchased its supply of drugs for lethal injection using a DEA registration number belonging to the Huntsville Prison Unit Hospital that closed 28 years ago. The DEA requires renewal of this registration information every three years, so if renewal occurred, the registration information was false. Controlled substances such as these drugs must also be stored and dispensed from a pharmacy, hospital or clinic with appropriate DEA registration, according to a prescription written by a physician who is also registered with the DEA. In summary, the TDJC illegally obtained and its employees are in illegal possession of injectable pentobarbital, a schedule II controlled substance. Scott Henson speculates in a blog post that this situation has arisen because the University of Texas Medical Branch at Galveston will not allow TDJC the use of their various state and federal authorizations to handle controlled substances as part of their contract to provide medical care to Texas state prison inmates.

Purchase from H. Lundbeck A/S: The Danish company Lundbeck was misled by the old prison hospital DEA registration number and supplied Texas with pentobarbital. Since my three earlier posts, they have published the company's Detailed Position on the subject. I am confident that their letters to Governor Perry and TDJC were not heeded.

Shortage of injectable alfentanil

The American Society of Health-System Pharmacists reports a shortage of injectable alfentanil. As you might suspect from its name, alfentanil is a derivative of fentanyl, another opioid analgesic which is in short supply. Hospira produces the generic version of both, and has made separate statements that manufacturing delays are due to quality improvements and that it is increasing production of fentanyl. Alfentanil is used for pain relief during surgery. A more expensive brand name version, Alfenta, is manufactured by Akorn. It is also in short supply, probably due to the shortage of the generic version.

Shortage of injectable pancuronium

The American Society of Health-System Pharmacists reports a shortage of pancuronium for injection. This drug shortage impacts surgery and intubation. In both procedures it is used to temporarily paralyze the skeletal muscles. This is an instance in which changing to one of the alternatives can cause confusion and errors because medical personnel may not be familiar with the different time of onset, duration of effect (see table), and the agent used to reverse the effects. For example, pancuronium's effects are routinely reversed with neostigmine, but if you use succinylcholine to paralyze the skeletal muscles, neostigmine increases the effect.

Injectable pancuronium is the second drug administered for lethal injection, and Hospira is now the only US-approved manufacturer. This further complicates the implementation of death warrants because of the shortage of injectable pentobarbital, the first drug administered for lethal injection. Links to my previous posts are given below.

Shortage of injectable pentobarbital for execution by lethal injection 

Shortage of injectable pentobarbital for execution by lethal injection - Update

Shortage of multiple vitamins for infusion

The American Society of Health-System Pharmacists reports a shortage of multiple vitamins for infusion. The key to this shortage seems to be that the shortage of adult MVI leads to a shortage of pediatric MVI because the latter are used for adults instead of for children less than 2.5 kg or less than 36 weeks gestational age. I infer this from the bulletin's statement:

Use of pediatric intravenous multivitamins for adults is not recommended and may result in a shortage of pediatric products

The bulletin also gives another hint at the problem by listing an alternate supplier, Baxter, for both pediatric and adult MVI. Evidently multiple suppliers is not enough to solve the problems caused by manufacturing delays at Hospira. 

Am I interpreting this situation correctly? Comments are welcome.

Shortage of injectable sulfentanil

The American Society of Health-System Pharmacists has announced a shortage of injectable sulfentanil. As you might guess from its name, sulfentanil is related to fentanyl, which has also been in short supply. Both are powerful opioid narcotic analgesics used for pain relief and anesthesia. Baxter cannot give a reason for the shortage of sulfentanil. The company recently sold its injectable fentanyl products to West-Ward, which likewise cannot give a reason for its fentanyl shortage. Hospira cites increased demand for both products as the reason for its shortages, which makes sense since these are the only three manufacturers.

As per my series of posts (primaquine tablets, injectable pentobarbital, calcium acetate capsules,  tetracycline capsules, injectable capreomycin, injectable atropine, injectable metoprolol, injectable levofloxacin, cilostazol tablets, injectable etomidate) on drug shortages, and as you may have read elsewhere, this problem is becoming acute.  In January 2011 Bona Benjamin, ASHP's director of Medication-Use Quality Improvement stated,  "For the past year-and-a-half we've seen quite an escalation in the report of drug shortages, and resolving the shortages is becoming more difficult."

I have yet to post on cancer drug shortages and the gray market in drugs. Sarah Kliff of the Washington Post recently interviewed US Representative Diana DeGette (D-CO), who introduced a bill last June requiring manufacturers to warn the FDA of impending shortages. This is particularly important for cancer drugs so that a course of treatment is not interrupted or delayed. Tom Rooney (R-FL) is a cosponsor, and US Senator Amy Klobuchar (D-MN) has introduced a companion bill in the Senate.