Dr. John Happel | Sep 22, 2018 | 0
Compounding Sclerosants for Use in Phlebology – Are Cost Savings Worth It?
Pharmaceutical-grade Sclerosants vs. Compounded Agents for Sclerotherapy of Varicose and Spider Veins
Varicose and Spider Vein Sclerotherapy: The Benefits of Compounding vs. Pharmaceutical-grade Sclerosants
The compounding of medications is intended to fill a niche where an individual can obtain a distinctive product to meet a particular and very patient specific need.
The criticism that compounding pharmacies face is that they are shifting the focus from this intended patient specific practice to a large scale mass-produced product for profit.
In doing so some say they that they are deliberately and intentionally attempting to avoid the scrutiny of government oversight and FDA testing.
Presently, since there are already two FDA approved medications for practical use in sclerotherapy, why consider using compounded agents at all?
Advantages and Disadvantages of Using Compounded Agents for Sclerotherapy
1. Cost of FDA Approved Sclerosants
Cost of sclerosants is a big consideration when choosing compounding pharmacies over Mertz and Mylan which produce the only two FDA approved sclerosants available in the United States.
The initial purchase price of 10 cc of 3% of Sotradecol or sodium tetradecyl sulfate (STS) is $289.00.
The initial purchase price of 10 cc of 1% of Asclera or polidocanol (POL) is $113.00.
The initial difference in cost is deceiving.
Its deceiving because of the difference in strength (1% vs. 3%).
It’s also deceiving because Sotradecol is approximately twice as strong as an equivalent strength of polidocanol.
After diluting Asclera POL to the equivalent strength that is optimal for spider veins, Asclera is actually 2.6 times the cost of Sotradecol.
For spider veins, common strengths of Sotradecol also known as Sodium tetradecyl sulfate (STS) range from .1% to .15%.
With Asclera (polidocanol or POL), commonly used strengths of .3% to .5% are often used for the treatment of spider and reticular (feeding) veins, respectively. For reticular veins, some doctors prefer to make the solution into a foam.
Diluting these medications in the vein office is commonly performed to achieve the desired concentration.
Common dilatants include normal saline, .45% normal saline, or sterile water for injection.
Using .45%NS and sterile water tend to make the final solution slightly stronger which results in increased effectiveness and increased endothelial wall and vessel destruction.
2. Unique Strength of Sclerosants
Another advantage of using compounded sclerotherapy agents is one can use a unique strength of a medicine for an individual patient that is not available from Mylan or Mertz, the two FDA approved manufacturers of POL and STS.
For example, suppose you want to inject 3% POL into varicose veins or the saphenous veins.
There is no FDA approve pharmaceutical company in the United States that can provide polidocanol at that strength.
3% polidocanol manufactured in Germany (Aethoxysclerol) is available only in Europe, Asia, South America, but not in the United States.
Asclera comes from the manufacturer at a maximum strength of only 1%. That is why Mertz recommends that it only be used for spider or reticular veins.
3. Legal Problems if There is a Complication
A disadvantage of compounding is that there may be legal repercussions if the using the compounded solution results in an adverse effect or a complication.
The most common complications with legal implications when using compounded sclerosants include mycobacterium or other infections, blood clots, or anaphylaxis.
When considering utilizing a compounded sclerosant, the vein specialist should closely consider the following questions should problems or complications arise after the vein treatment.
Questions that could be raised by an attorney when there is an FDA approved pharmaceutical grade alternative to compounded vein sclerosants include:
- Where was the solution compounded? (in-state or out-of-state)
- When was the solution compounded? (expiration date)
- Is the compounding pharmacy registered with the FDA?
- Was the compounding solution purchased in bulk or for an individual patient?
- How was the compounded solution stored?
- How was the compounded solution tested for safety and efficacy?
- Were histologic studies done on veins treated with these compounded solutions?
- Was the compounded solution chosen because it was cheaper or to increase profit or was there a better reason that it was chosen?
Impurities and significant differences in strength (inconsistent strengths) were found in comparing different compounded solutions from different compounding pharmacies.
The following article was written by Dr. Mitchel Goldman about the impurities issue in regards to carbitol found in compounded STS sodium tetradecyl sulfate.
Carbitol is also a solvent also used in wood stains, industrial cleaners, lacquers, varnish and brake fluids.
Dr. Listor in 1851 was a huge proponent of carbitol or carbolic acid in medicine for sterilization. He first studied its use in compound fractures in which bones protruded from the skin. In the Victorian age, people believed that infections came from poisonous air.
Listor found that cleansing the fresh wounds of amputees with carbitol reduced the rate of infection. Infection rates plummeted when Listor used carbitol to wash hands and scalpels, dress wounds, and sterilize sutures. Along with Louis Pasteur, Listor gained fame suggesting that germs rather than bad air was the cause of infections.
Here is a summary of the Goldman article about the use of the “contaminant”, carbitol, in compounded Sotradecol.
The objective was to determine the composition of three available solutions of sodium tetradecyl sulfate from compounding pharmacies in comparison to pharmaceutical-grade sodium tetradecyl sulfate, Fibrovein (STD Pharmaceuticals, Ltd.).
Solutions of 3% sodium tetradecyl sulfate were obtained from three compounding pharmacies. An analysis of their composition was performed.
All samples of 3% sodium tetradecyl sulfate obtained had a different concentration of sodium tetradecyl sulfate than that stated on the bottle (range, 2.59%-3.39%). Significant concentrations of the contaminant carbitol were present in samples from all three sources (0.33%-4.18%).
The production of 3% sodium tetradecyl sulfate by these three compounding pharmacies appears to occur by simple dilution of a 27% industrial detergent solution that is not manufactured for use in humans. Physicians need to be aware that the stated concentration may not be correct and that along with sodium tetradecyl sulfate, potentially harmful contaminants may be present in the solution.
Choice of whether to use FDA approved pharmacy grade sclerosants vs. compounding usually comes down to the cost.
If the strength of solution is not available, compounding can be justified after considering the safety issues discussed in this article.
However, the most important principle in performing successful sclerotherapy is to cause irreversible endothelial damage resulting in vessel destruction of the targeted veins.
This must be accomplished while also avoiding damage to normal veins and the overlying skin and also avoiding hyperpigmentation.
The lowest effective strength and volume of the “best” sclerosant should be used to maximize effectiveness and avoid complications.
It’s like a tight-wire act.
Avoiding dangerous, inconsistent, or ineffective solutions compounded at an untrustworthy pharmacy is risky for the patient and raises liability and moral issues for the physician.
Using meticulous safety measures while mixing these solutions, proper sclerosant concentration, volume, and the technique used during the procedure itself can be more important than the choice of the sclerosant itself.