There are a number of options for testosterone replacement therapy including topical options (cream and gels), patches, troches, injections and pellet implantation.  Each method has its advantages and disadvantages.

Creams and gels.  Creams and gels are perhaps the most popular methods of testosterone replacement.   There are a number of commercially available replacements available including Androgel® and Testim®.  These products contain natural testosterone and they are relatively easy to use.  Four disadvantages of commercial testosterone replacement gels are 1) they are expensive ($350/month), 2) they contain a fixed dosing which may or may not be an appropriate dose for you, 3) the amount of gel needed to be applied is large and often the whole torso needs to be covered for each application and 4) they contain large amounts of alcohol which may be irritating to some men.  Compounded testosterone replacement is usually less expensive, has infinitely flexible dosing, does not contain alcohol and usually comprises a volume that can be easily applied to a small area, such as the inner thigh.  One disadvantage to all creams applied to the skin is the skin itself.  The skin is a formidable barrier to molecules both entering and leaving the body.  This is the skin’s main purpose.  Sometimes, no matter what we do to try to get drugs through the skin, we cannot overcome the barrier properties.

Patches.  Androderm® patches are effective at administering testosterone across the skin.  They contain penetration enhancers that overcome the barrier properties of the skin and deliver a consistent and constant delivery of testosterone.  Three disadvantages of patches are 1) they tend to be very irritating to the skin, 2) they are only available in 2 and 4mg/day fixed dosing, 3) they are conspicuous when worn and are easily visible to others and 4) they are expensive ($360/month).

Troches.  Unlike the skin, the mucosal lining of the mouth is more permeable to molecules entering the body.  Sometimes, if application to the skin does not provide adequate testosterone levels, dissolving a waxy or gummy-bear like tablet (troche) between the cheek and gum or under the tongue will provide improved testosterone levels and will improve symptoms.   The main disadvantage of troche delivery is that not the entire amount of testosterone is absorbed across the mucosa.  Obviously, some is going to be swallowed with the saliva.  When testosterone is swallowed, it is readily deactivated by the liver.  In addition, orally administered testosterone can negatively impact lipid levels (cholesterol, triglycerides, etc.)  If troches are chosen as the method of delivery, physicians should keep a close eye on blood chemistries to ensure that the swallowed component of a troche is not adversely affecting your body.

Injections.  Injections can provide an efficient and cost-effective way to administer testosterone.  Obviously, any molecule injected into the body will make its way into the blood stream.  The main disadvantage of injectable testosterone replacement is the injection itself.  Some men are capable of self-injecting, some are not.  If not, this method of administration may necessitate multiple trips to the physician’s office for injections.  Many physicians believe that testosterone cypionate,  testosterone enanthate and testosterone propionate are long acting forms of testosterone and only need to be administered monthly.  This is simply not true.  These injections need to be administered multiple times per week and, at a minimum, one per week.  Otherwise, the resulting high and low levels (called peaks and troughs) stimulate aromatase production and results in higher estrogen levels.  The second disadvantage with injections is that the oil used as a carrier or vehicle can be irritating.  Commercial products are made with cottonseed oil.  Sometimes this oil is irritating to the tissues surrounding the injection sites.  Keystone Pharmacy is compounding products with much gentler sesame oil to help alleviate this problem.

Pellets.  Pellets are small waxy like rods that are inserted under the skin.  In theory, they are designed to slowly release testosterone over the time of 3 to 9 months at which time, new pellets are inserted.  This is a viable method of testosterone replacement but must be administered in a physician’s office, is relatively expensive and is irreversible if the therapy is poorly tolerated.  Keystone Pharmacy does not make testosterone pellets.  We have attempted them in the past but have found them too difficult to sterilize.  If you choose pellet therapy, ensure that your doctors is obtaining them from a PCAB accredited pharmacy and as to see testing records that demonstrate that your lot of pellets is sterile and free from contaminants called endotoxins.

Next month, we’ll examine the safety of testosterone replacement therapy.

Dr. Dave
Keystone Pharmacy Owner and Chief Formulation Scientist

The last two tests are DHEA and cortisol. If someone is stressed, their hormones are forced down the cortisol pathway. This leaves the “sex hormone” part of the cascade undersupported. DHEA is the immediate precursor to androstenedione which is an immediate precursor to testosterone. If DHEA levels are low, sometimes we can fix low testosterone levels with simple DHEA supplementation.
This is part 1 of a 3 part discussion, stay tuned and give us your thoughts!
David Miller, RPh, PhD Owner and Chief Formulation Scientist

PCAB accredited compounding pharmacies are held to a very high standard. Recognizing that compounding standards varied widely from pharmacy to pharmacy and state to state, PCAB was established by to following organizations in an effort to standardize care:
• American College of Apothecaries
• American Pharmacists Association
• International Academy of Compounding Pharmacists
• National Association of Boards of Pharmacy
• National Community Pharmacists Association
• National Council of State Pharmacy Association Executives
• National Home Infusion Association
• United States Pharmacopeial Convention (USP)

These organizations recognized that quality control among compounding pharmacies varied from very good to very poor. The Pharmacy Compounding Accreditation Board established rules and standards by which they would judge a pharmacy’s worthiness of accreditation.

Thursday and Friday of this week, we had a surveyor from PCAB at Keystone Pharmacy. The accreditation process is not easy. Our surveyor was VERY thorough. She reviewed all of our training records, our standard operating procedures, our policy and procedures, our testing records and evaluated our team in action. I was very pleased with the way the survey went and surveyor was very complimentary of our compounding operation. It was very helpful to have an outside, independent evaluator assess Keystone Pharmacy’s compounding operations.

Does Keystone Pharmacy have to be accredited in order to make your compound. The simple answer is no. Keystone Pharmacy is accredited because we recognize the serious nature of what we do and how it impacts your health and well-being. We are very proud of what we do and strive to be the best compounding operation anywhere. We hold ourselves to the highest possible standards and you should accept nothing less.

After all, you would not accept a hospital that lacks accreditation. Why would you accept a non-accredited compounding pharmacy?

Interstitial cystitis (IC), also known as painful bladder syndrome, is a condition in which the tissues of the bladder wall become inflamed or damaged. Symptoms of IC are very similar to those of a urinary tract infection and as a result are often misdiagnosed. Early on, IC typically occurs in “flares” with occurrence and symptoms being sporadic (leading to a misdiagnosis of a UTI); however over time symptoms can become consistent and unbearable.  Most commonly patients will notice pain/discomfort during urination and intercourse, urinary frequency and urgency and urinary discomfort. Untreated, IC can lead to scarring or stiffening of the bladder walls and an inability to hold much fluid in the bladder. IC typically occurs in women but has the potential to occur in men as well.

The exact cause of IC is not yet known, however inflammation clearly plays a role.  Some contributing factors include chemicals in the urine aggravating damaged tissue in the bladder, auto-immune responses such as mast cell activation and histamine release, low estrogen levels and previous bladder damage. Patients with IC begin experiencing symptoms for no apparent reason or they may start following surgery, particularly hysterectomy and gynecological surgeries in women.

Treatment options are available for interstitial cystitis
A great place to start is by looking at diet and lifestyle. Many women say their symptoms abate when they follow an alkalizing, low-inflammatory diet by avoiding certain trigger substances. Here are some primary “triggers” to avoid:

1. Smoking
2. Alcohol
3. Coffee for both the acidity and caffeine
4. Tea, even decaffeinated, due to acidity.
5. Cranberry and other acidic fruit juices. Remember this is not an UTI.
6. Diet soda for acidity, caffeine, and the artificial sweetners.
7. Tomatoes and other acidic foods
8. Artificial foods, dyes and flavorings.
9. Foods that promote yeast, especially refined sugars.
10. Gluten which promotes inflammation in many patients.

The association with low estrogen and IC has been noted clinically and in the literature. Many physicians will try vaginal hormone replacement containing estrogens to control IC symptoms.

Although there is no accepted cure for IC, the main goal of current treatment is to alleviate symptoms. Unfortunately there is not one medication that can be given to every patient that will relieve all symptoms, so patients may receive a “cocktail” (a concoction of various medications).  These cocktails are administered intravesically, into the bladder, through a catheter; this is known as a bladder instillation.
Instillations can contain combinations of the following medications:
Heparin: aid in bladder restoration
Lidocaine: local anesthetic for pain
Sodium bicarbonate: enhance anesthetic penetration into mucous tissue
Rimso-50 (DMSO): anti-inflammatory
Dexamethasone: anti-inflammatory corticosteroid
Triamcinolone: anti-inflammatory corticosteroid

http://www.painful-bladder.org/pdf/IPBF%20Publ%2004%20UK.pdf

http://www.drrajmd.com/conditions/bladder/cystitis/cystitis.htm#Bladder Instillation

http://www.painful-bladder.org/pdf/IPBF%20Publ%2005%20UK%20booklet.pdf

Enter the YELLOW JUG program in 2009. http://www.greatlakescleanwater.org/id17.html

Background:
Each year large amounts of pharmaceutical chemicals are exposed to the environment as evidenced by an AP investigation that found US drug companies and other manufacturers dump 271 million pounds of pharmaceutical waste into water sources each year. This same investigation revealed that hospitals and long-term care facilities create an additional 250 million pounds of pharmaceutical waste. The general public is also contributing to this problem by letting 200 million pounds of unused medications enter the country’s sewer systems. There is increasing evidence that these chemicals can be found in many zones of our environment, and that these chemicals are having an effect on wildlife. In addition, these chemicals are also making contact with human populations in the United States.
A USGS study of Boulder Creek in Colorado revealed detectable levels of the antibiotic, sulfamethoxazole, caffeine, and triclosan, an antimicrobial found in soaps. Waterways near drug manufacturers in Michigan and Delaware have also shown higher levels of antibiotics and codeine. In the Western areas of the country, where the summer months often present drought conditions, farmers must use treated wastewater to irrigate their fields. Samples taken from Colorado farms are showing that common household medications are being deposited in the soil and remaining there for several months. Some of the medications detected were antidepressants, anticonvulsants, and anticoagulants. More common medications were also found including Tylenol, caffeine, nicotine, and Benadryl. This evidence shows that medications are reaching the environment both in water and on land.
The next concern is whether the amounts of pharmaceutical chemicals found in the environment are capable of impacting wildlife. Even though contaminants were found at “safe” levels, the Boulder Creek study found that fish are displaying both male and female sex organs, and there is a disproportionate number of female fish for every male. Increased amounts of sex hormones in aquatic ecosystems have led to hormonal changes in fish species that lead to reproductive dysfunction. This occurrence has been seen nationwide, most significantly in Lake Mead, Nevada and the Potomac River of Maryland. Another study conducted by the USGS in Fourmile Creek, Iowa detected levels of commonly used antidepressants in stream water, stream bottom sediment, and in fish tissue. The medications Effexor, Wellbutrin, and Celexa were detected at the highest level in stream water, with Effexor and Prozac found at the highest levels in bottom sediment. White suckers are a native fish species to Fourmile Creek that displayed a measurable amount of Zoloft and Prozac embedded in brain tissue of the fish. Scientists have also found that frogs and other species can be harmed by low concentrations of certain medications. These findings provide insight that the amounts of pharmaceutical compounds found in the environment is high enough to impact wildlife.
The implications of these findings on the human population are largely unknown. Pharmaceutical chemicals have been found in the drinking water of 51 million people in the United States, but all of these were detected at very low levels that are considered safe for human consumption. However, many chemicals do not have a determined safe upper limit, and it is unknown at what level many chemicals begin to cause damage. Further research is needed to determine the safety of the many different chemicals being found in the country’s water ways.
Due to the detection of pharmaceutical chemicals in the environment and their known harm to aquatic wildlife, it is important for the general public to utilize medication disposal programs to minimize the amount of harmful chemicals released into the environment. The uncertainty of how pharmaceutical contaminants impact human health only adds to the importance of reducing pharmaceutical waste.

Often, we are the “face” of your insurance company and bear your frustrations. It is easy to lash out at us because we are the bearers of bad news either on the phone or in person. The truth is, Keystone Pharmacy has absolutely no influence or control over your insurance company. They dictate everything, period.

Let me try to explain a few things to make it easier.

1) Insurance companies work on a formulary system. They determine what will be covered based on internal guidelines and guidelines mandated by law. Formularies are determined by many criterions including 1) cost of the drug dispensed, 2) therapeutic utility of the drug (e.g. how useful a drug will be), 3) alternative therapies that may exist in the market place (e.g. are there lower priced alternatives available) and 4) rebates paid to the insurance company by the drug manufacturer. If a company wants their drug to have preferred status, they must either have a significant therapeutic advantage over competing drugs in the marketplace or make their drug financially appealing to the insurance company. Failure to do so will result in either the drug being left off the formulary or a higher copay being charged for the drug.
2) Insurance companies often work on a tiered copay system. You may have 3 or more tiers of copays for your prescriptions. The lowest tier is often for generic medications. The middle tier is reserved for “preferred” brand name medications and the highest tier is reserved for “non-preferred” brand name medications. Compounds likely fall in the highest tier copay because we do not have a mechanism to provide rebates to the insurance companies.
3) Your prescription should cost the same no matter where you go. I have people calling all of the time asking what our cash price is for a prescription. As is often the case, they have a percentage copay and are trying to find the cheapest source figuring that their copay will be a percentage of the lowest retail price. The truth is, the percentage is based on a “negotiated” price between the insurance company and the pharmacy. All pharmacies have the same contracts so the negotiated prices will be the same no matter where you go. Hence, your percentage copay should be the same wherever you go.
4) Medicare will not cover compounded medications from bulk ingredients. Provisions in the Medicare Part D act of 2005 exclude compounded medications from bulk active ingredients. This was done largely to appease the large pharmaceutical manufactures without input from community, compounding pharmacies or the patients we serve. We believe this to be a travesty and would like it corrected, but the wheels of congress are moving very slowly right now. Compounded medications actually end up costing a small fraction of the amount charged for commercially available manufactured products. Changing the law to allow for compounded medications to be covered by Medicare Part D plans would actually save US taxpayers billions of dollars, yet no change seems imminent.
5) Medicaid will not cover compounded medications. Medicaid works purely on a rebate system. To be included on Medicaid’s formulary, a manufacturer must give rebates to the state. As a taxpayer, I am for this. As a compounding pharmacist, I am obviously opposed. Because we work almost exclusively with non-rebated chemicals, most of what we use in our compounds will not be rebated and therefore excluded from the formulary. Medicaid officials will argue that they do cover compounded medications, but by the time all of the non-rebated chemicals are excluded from the price, they end up not paying anything.

I hope this helps explain why coverage and copays are what they are. I also hope it demonstrates how little control Keystone Pharmacy has over your copay and your insurance company’s decision to cover or no cover your medication.

Thanks for your understanding of this matter. Insurance is not only frustrating for you, it is the most frustrating part of our job, too. We spend almost infinitely more time with insurance issues than we do with patient care. We share your pain.

Dave

Wolverine construction and Dean are doing a great job keeping us functioning during this transition. Our laboratory is up and functioning in a temporary space. Everyone is working very hard to continue to provide the same level of service that you have come to know and expect from Keystone.

Thank you for your patience during our transition. I appreciate your business and look forward to making your experience with Keystone Pharmacy even better in the near future.
Dave