FDA ‘Safety Initiative’ Now Means an Ounce of Ethanol Costs $30,000

Ethanol locks are now going to be ridiculously expensive (possibly $30,000 per month -for 1 oz) due to an FDA initiative which aims to improve drug safety. Paradoxically, this could endanger the health of many vulnerable children.

Modern Healthcare: Unapproved Drug Initiative adds up to $30 billion in healthcare costs Thanks to Jennifer Sterner-Allison for this reference.

An excerpt:

A regulatory pathway that aims to ensure drug safety is inflating healthcare spending by billions of dollars, according to a new report.

Four widely used drugs funneled through the Unapproved Drug Initiative will increase spending by more than $20.25 billion over a five-year span as manufacturers hiked prices between 525% to 1,644%…

“Hospitals are absorbing additional cost for drugs that are not innovative, not curing new diseases, do not have overwhelming R&D investment, and are often the preferred drug of choice.”…

The 2006 Unapproved Drug Initiative requires manufacturers to pull these drugs and prove to the FDA that they are safe. Typically, fewer manufacturers remain in the market after the FDA intervenes, which allows price manipulation.

Drugs that go through the UDI pathway can earn the manufacturer up to seven years of patent protection, which can prevent competition. At minimum, other suppliers of the drug targeted by the UDI also have to leave the market and receive approval, which can reduce competition.

The situation with ethanol is particularly egregious, said Erin Fox, a drug shortage expert and senior director of drug information and support services at University of Utah Health.

Belcher Pharmaceuticals is charging $1,000 per milliliter, which equates to $30,000 for one shot of ethanol, since it received an orphan drug designation through the UDI, granting Belcher’s drug exclusivity through 2025, she said. Belcher won the orphan drug classification, a status for drugs that treat rare diseases, for its treatment of hypertrophic obstructive cardiomyopathy.

“It is the perfect example of how this FDA approval process is broken,” Fox said. “Pediatric hospitals are going to be particularly impacted because ethanol is sometimes used to ‘lock’ IV ports to prevent infections in high-risk patients.”..

“FDA’s Unapproved Drug Initiative continues to have serious unintended consequences and in my opinion should be halted,” she said

My take: I have contacted the American Academy of Pediatrics and asked them to try to work on this problem.  The high cost of ethanol may prevent its routine use and result in central line infections, hospitalizations and even death in vulnerable children.

Related blog posts (on utility of Ethanol Locks):

Blogs related to Pharmaceutical Practices:

Ethanol locks can minimize infections among patients who receive intravenous nutrition (“TPN”) which was popularized by Dr. Dudrick.  Due to the exorbitant costs of ethanol, this may lead to increased infections, hospitalizations and even death.


Antibiotic Selection for Suspected Central Line Infections

A recent study (BP Raphael et al. JPGN 2019; 70: 59-63) describes 309 central line-associated bloodstream infections (CLABSI) in 90 children were dependent on parenteral nutrition (median age 3.8 years).

Key findings:

  • 60% of isolated organisms were gram-positive, 34% were gram-negative, and 6% fungi.
  • For gram-positive organisms, 51% were sensitive to methicillin
  • For gram-negative organisms, 71% were sensitive to piperacillin-tazobactam, 97% to cefepime, and 99% to meropenem

Based on these findings, the authors advocate the following:

  • “Vancomycin and cefepime provide improve coverage over vancomcyin piperacillin-tazobactam for” CLABSI
  • Empiric use of vancomycin and meropenem “may be justified” in septic shock “where maximal probability of cure outweighs risks of long-term drug resistance”
  • If there is an increased fungemia risk, such as prior fungal infections, shock, or immunodeficiency, the authors recommend adding fluconazole

Another advantage of cefepime over piperacillin-tazobactam is a reduced risk of acute kidney injury which has been associated with the latter.

My take: Individual institutions may have variable organism sensitivity.  In the absence of institutional data, this recommendations are a good starting point.

Related blog post: #NASPGHAN19 Intestinal Failure Session Part 1

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Old Montreal

One More Way to Prevent CVL Infections

While a recent study (JPGN 2014; 59: 177-81) discusses the results of several strategies for limiting CVL infections, I found one approach in particular of interest.

This single center study (2009-2013, n=48 children) from Birmingham, UK examined a multidisciplinary enhanced care pathway regarding CVL care.  Implementation of this pathway lowered the risk of all-cause line infections from 1.98 per 1000 parenteral nutrition days to 0.45.  The pathway included training care providers, careful discharge planning, having those with skin conditions see dermatologists, and monitoring compliance.

One important observation was that methicillin-sensitive Staphylococcus aureus (MSSA) infections were often preceded by local signs of infection for a short period prior to systemic infection.  “We devised a pathway for exit site infections in which a swab is taken and empiric topical mupirocin commenced immediately. A decision on any further management is made after 24 to 48 hours.”

Take-home message: Implementing a CVL care pathway lowers CVL infections.  Implementing topical therapy at the first signs of a localized infection can be an important part of this effort.

Related blog posts:

Nutrition Module

More notes from this year’s postgraduate course:

Clinical issues in parenteral nutritionPraveen S. Goday, MBBS, CNSC (page 105)

  • Fish‐oil vs minimizing soybean oil‐based lipid emulsions
  • Catheter‐related bloodstream infections (CRBSI): Ethanol locks “Humans like ethanol and bacterial don’t.”  Meta‐analysis:  In comparison with heparin locks, ETOH locks (various regimens) reduced the following: a) CRBSI‐rate per 1000 catheter days by 7.67 events (81% ↓)  b) catheter replacements by 5.07 (72% ↓), c) 108‐150 catheter days of ETOH lock exposure were necessary to prevent 1 CRBSI, d) Adverse events – rare and included thrombotic events.  Reference: Oliveira et al. Pediatrics 2012;129:318–329

Parenteral Drug Shortages: All PN products except dextrose and water have been in short supply at some point since spring 2010

Imported components from Europe (higher cost)

• Peditrace™ – zinc, copper, manganese, selenium, fluoride, and iodine

• Addamel N™ – zinc, copper, manganese, selenium, fluoride, and iodine, molybdenum, iron, and chromium

Summary / Take‐home points

  • Reduction in soybean oil emulsion or provision of fish oil emulsion results in improvement in cholestasis
  • Ethanol lock therapy decreases CRBSI in children on home PN
  • Significant PN shortages have affected our ability to care for our PN patients; thus need vigilance and good communication between physician, dietitian and pharmacist

Severe Obesity in Your Clinic: The disconnect between the epidemic and the intervention Sarah E. Barlow, MD, MPH (page 125)

What to do for obesity?

  • Behavior modification
  • Pharmacotherapy (and behavior modification)
  1. Orlistat (Xenical, Alli) -Enteric lipase inhibitor, FDA approved starting at age 12 years (OTC $200 per month)
  2. Approved for adults Lorcaserin (Belviq): 5-HT2C agonist
  3. Approved for adults: phentermine and topirimate (Qsymia)
  • Surgery (and behavior modification)
  • Meal replacement (and behavior modification)

Orlistat trial for adolescent obesity:

  • 54 week double-blind RCT
  • 539 subjects: 12 to 16 years of age, BMI 36 ±  4 kg/m2
  • BMI change kg/m2 (mean):  – .55  vs. + 0.31 for control
  • Fecal urgency (%) 20.7 (11.0 in controls)
  • Flatulence (%) 9.1 (4.4 in controls)
  • Fecal incontinence (%) 8.8 (0.6 in controls)
  • Reference: Chanoine et al. JAMA 2005;293:2873

Orlistat meta-analysis among adults :

  • -2.87 kg [95CI -3.21, -2.53] = placebo-subtracted change at 1 year
  • Reference  Rucker D. BMJ 2007;225:1194

Multiple potential medications are being studied

Selection criteria for adolescent bariatric surgery

  • Tanner stage IV or V
  • BMI ≥ 35 kg/m2 with severe
  • Comorbidity or BMI ≥ 40 kg/m2 with comorbidity
  • “Have failed” 6 month of organized attempts at weight loss
  • Committed to pre and post medical and psychological care
  • Supportive family
  • Able to give informed assent
  • Frequent barriers: Distance from center, Insurance, Age, Reluctance
  • Reference: Pratt Obesity 2009;17:901

Complications from Surgery

  • For all procedures: nutritional deficiencies, especially iron, vitamins B12, D, and thiamine
  • For gastric bypass: postprandial hypoglycemia in adults
  • For lap band: need for re-operation for slippage or erosion in adults and small adolescent study.
  • Also pouch dilatation
  • For sleeve gastrectomy: leak or bleeding along suture site


  1. 4% of children 6 to 19 are severely obese
  2. Severe obesity leads to high levels of cardiovascular disease risk factors, NAFLD, OSA, and pre-diabetes
  3. Behavior modification has modest efficacy, is a partner in all other intensive interventions, but is not readily available behavior modification is underutilized because it is time-intensive and resource-intensive.  It it is necessary even though it is not sufficient.
  4. Orlistat is the only medication currently available for adolescents.

 5 2 1 0

  • 5 servings of fruits and vegetables a day
  • 2 hours or less of screen time
  • 1 hour (60 minutes) or more of physical activity
  • 0 sugar-sweetened beverages

Postgraduate Course Syllabus (posted with permission): PG Syllabus

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and specific medical interventions should be confirmed by prescribing physician.  Application of the information in a particular situation remains the professional responsibility of the practitioner.

Ethanol locks -jump on the bandwagon


From Nutrition in Clinical Practice, published online before print, December 11, 2012, doi:10.1177/0884533612468009 (Thanks to Kipp Ellsworth for this link from his twitter feed):

“Our group of patients (n=14) showed a 73% reduction in CABSIs and a 77% reduction in catheter removal due to infection after ethanol lock therapy. In our patient population, weekly ethanol lock therapy for 2 hours is an effective technique to reduce CABSIs and catheter removal in long-term home PN patients.”

CABSIs =catheter-associated bloodstream infections