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Category Archives: Compounding
June 17, 2017 : looking back hardly a day or two goes by since this year began when a question about medical marijuana or as we call it out here “marijuana” and what is going to happen next July when it becomes real is asked. Last month I was asked by a group of Nurse Practitioners to present on a topic I rarely speak about but fill prescriptions for often – BioIdentical Hormone Replacement Therapy. I like to use the term supplement instead of replacement but it really made me think about the tough upward climb this category has had and continues to have based on a few position statements from such groups as SOGC and NAMS.
Looking at the marijuana issue, never before have we seen a couple of ingredients leap onto the potential healthcare market with the claim to relieve or cure so many, many health issues. Never before have so many N of 1, anecdotal reports driven an entire category of mostly unproven therapies. Granted there are some valuable uses of the drug that have been used for years but many have been very overblown with the main selling point of “no one has died”.
Turning to my upcoming presentation, I started mulling over the studies that have shown for years the benefits and limitations of all types of hormone therapy that I have collected and still continue to collect on the topic. Speaking to the public on a subject is different than talking to medical professionals. I speak to both groups all the time on all topics. To narrow down an hour worth of meaningful, compelling, convincing data that flows easily on a medical treatment that is foreign to a professional group so that you don’t lose them is daunting.
If I present on a topic I have a clear conflict of interest with such as this, I always open with that and some literature from the other side of the argument. There is no problem here with BHRT as lots of naysayers exist. In truth, I have found there are as many cases of overblown promises with BHRT and there are complete opposite downplay of any proven benefits and exaggeration of adverse effects. A segment from Climacteric from just this year was the best I could find that slammed this type of therapy over a dozen sentences. We now see less of an issue with the term BioIdentical, since estrogen and progesterone are both found in the commercial prescription drug industry in Canada more and more in a bioidentical form, especially since the Women’s Health Initiative Study over a decade ago that effectively stopped conjugated equine estrogen and medroxyprogesterone acetate from being dispensed overnight. So at least Big Pharma has caught up with compounding in some ways.
I continue in my talk to disprove the issues just laid out from the climacteric slide: that hormones do pass predictably through human skin and give resultant increases in the body (given the correct fluid is tested), that the stability of the hormone in the right base is predictable, that saliva testing is legitimate and useful in showing levels of active hormones (especially for topically applied hormones), and that all hormone therapies have benefits and risks associated with them, regardless of what hormone therapy that entails.
Given the criticisms the WHI received, one thing we did find from the CEE/MPA regimen was the decrease in fracture risk. With the older average age of the subjects in that study and the lack of topical hormone or actual BHRT used, there is very little to pull from that study for this talk. There are however many studies that can and do show the benefit of BHRT. Most of these are smaller studies than we are used to in the prescription world. One point to take away though is we have seen a top seller in our prescription market fall away to nothing and the public is looking at us and asking how could we be so wrong all these years about something that was so blatantly clear in a study that it cut the study short? Evidence slowly grows on bioidentical hormones but is showing even to our commercial drug industry that it is a safe benefit.
The International Journal of Pharmaceutical Compounding published a three part study on the topic of BHRT. In this small study, surveys were given to women on HRT. The response rate was 70 on BHRT and 53 on synthetic hormone therapy. Each survey consisted of 15 questions that probed such topics as symptom relief, reasons for starting hormone therapy, side effects, age of starting therapy and type of therapy. In the areas of hot flashes, night sweats, sleep quality, dry skin/hair, vaginal dryness, foggy thinking, mood swings and decreased libido, bioidentical therapy outperformed synthetic therapy in all counts. In side effects from therapy, bioidentical was preferred over synthetic for side effects like difficulty sleeping, weight gain, breast tenderness, bloating, upset stomach, breakthrough bleeding, foggy thinking, mood swings and leg pain. Drowsiness occurred more frequently with bioidentical than with synthetic.
A huge concern with bioidentical and compounded hormones is the threat of cancer in hormone therapy. In 2008 a study that looked at over 80,377 post menopausal women, 2354 of them developed invasive breast cancer. Compared to the women that never used HRT, estrogen alone therapy was associated with a 1.29 fold relative risk, 1.69 with estrogen/progestagen and a relative risk of 1 with the estrogen/progesterone women.
In other studies we have seen the benefits from BHRT in areas of insulin resistance, blood pressure, lipids, endothelial function, arteriosclerosis, thrombotic risk, and neuroprotection. More and more we are seeing studies unfolding showing not only is BHRT a healthy and safe option for women of all ages but is also brings quality of life to these patients that they have lost since the Women’s Health Initiative Study came out. Saliva testing for topicals is also shown to be useful as topically applied hormones aren’t reflected in blood draws like oral is. Oral hormone therapy has shown itself to be an unhealthy route for women and topical application has proven itself to be the preferred choice longterm.
So yes, thank you Marijuana, or more correctly CBD:THC. Your very sudden rush to the market has been touted for virtually every medical issue going right now. There are definite benefits in areas such as pain, perhaps PTSD (and a few others) but completely untested and unproven “benefits” in so many other areas. It has shown us that there are areas like BHRT that we’ve been told we had zero proof for but really do have volumes of proof when we compare it to the complete lack of proof in marijuana for many of the areas it is being used for.
Orozco ,P. et al. Salivary Testosterone is associated with higher lumbar bone mass in premenopausal healthy women with normal levels of serum testosterone. European Journal of Epidemiology 16:907-912,2000
Wright, JV. Bio-Identical Steroid Hormone Replacement. Selected Observations from 23 years of Clinical and Laboratory Practice. Ann.N.Y.Acad.Sci. 1057:506-524 (2005)
Hofling, M, MD et al. Testosterone inhibits estrogen/progestogen-induced breast cell proliferation in postmenopausal women. Menopause:The Journal of The North American Menopause Society. Vol 14, No.2, pp 183-190
Holtorf, MD. The Bioidentical Hormone Debate: Are Bioidentical Hormones (Estradiol,Estriol, and Progesterone) Safer or More Efficacious than Commonly Used Synthetic Versions in Hormone Replacement Therapy? Postgraduate Medicine, Volume 121, Issue 1, January 2009
Schwartz, E.T. MD. Hormones in Wellness and Disease Prevention: Common Practices, Current State of the Evidence, and Questions for the Future. Prim Care Clin Office Pract 35(2008) 669-705
Deleruyelle, LJ. Menopausal Symptom and Side Effects Experienced by Women Using Compounded Bioidentical Hormone Replacement Therapy and Synthetic Congugated Equine Estrogen and/or Progestin hormone Replacement Therapy: Part 3 . International Journal of Pharmaceutical Compounding Jan/Feb 2017 pp 6-16
Stephenson, K. MD FAAFP. Salivary Hormone Profile. International Journal of Pharmaceutical Compounding vol 8 no 6 November/December 2004
Wepler, ST. A Review of Bioidentical Hormone Replacement Therapy. International Journal of Pharmaceutical Compounding Vol.6 No.2, March/April 2002
When I graduated from Pharmacy school in 1993, topically applied preparations for pain relief were limited to lidocaine and capsaicin, or so I was told up to that point. I was also taught that narcotics were safe not only for short term pain relief but also for long term pain that was non palliative and non cancer related and that addiction was rare in cases where total pain relief had not been reached yet. Medication is a constantly evolving and changing world. 23 years has passed and all of this has changed in a drastic manner.
It’s difficult to know exactly how it all started, but many in the medical community like to lay blame on the shoulders of a company called Purdue that had its beginnings in New York City as a relatively small pharmaceutical firm in the early 1950’s when it was purchased by two psychiatrist brothers, Mortimer and Raymond Sackler. The success of OxyContin from this company generated billions of dollars in revenue and made the Sacklers one of the wealthiest families in the country. Unfortunately, we began to see a trend happening where claims of this company and the aggressive and inappropriate marketing practices resulted in the alarming abuse and trafficking of this medication over decades of use. The company had to pay 635 million dollars after executives plead guilty.
You’d think that would have been the end of it. However the Mundipharma associated foreign corporations are agressively marketing this same medication worldwide with no plans to scale back. They also are running training programs to physicians in these countries urging them to overcome “opiophobia” and to just go ahead and write for these painkillers. They also have campaigns urging patients to take what their doctors prescribe to them.
The issue now is we have created an entire continent of addicts who would not normally have been there without these recommendations. For example, Jane Doe gets in a car accident. She has undeniable pain from this and it is not handled with NSAIDS. She is given a narcotic based on the recommendations from companies like Purdue who claim their studies show this is a safe medication to prescribe in this patient. In a little while Jane needs a higher dose of the medication and after not too long, despite her repeated denials, is addicted to painkillers. She then is unable to get a continuous supply of the drug from her doctor who now recognizes the problem. She starts to purchase the medication off the street. Her addiction becomes stronger as her supply and quality of the medication becomes more and more questionable. She then finds herself injecting to keep up with her addiction. In the last number of years, she has lost her job, her husband, her children, her home, car, money, friends, and everything she owns is in a small bag that she uses as a pillow because she lives on the streets with a sole purpose of seeking her next supply of fentanyl.
Is this scenario typical of everyone on narcotics? Of course not. If you walked down Vancouver’s downtown Eastside and asked random passersby what their story is, you might hear this one. Canada has recognized this in a west – east manner this year. Canada’s largest mental-health/addictions hospital, the Centre for Addiction and Mental Health in Toronto called on Ottawa in November to remove these high dose opioids from the market and to launch a review of prescription painkillers across Canada.
In fact, in the last 4 years, the number of opioid prescriptions dispensed per 1000 population has decreased in the United States whereas in Canada the number has more or less remained the same over that time frame. The provinces in Canada have been steadily spending more and more each year on opioid addiction. Not surprisingly, BC has lead this spending. PEI and NB are 2nd and 3rd behind them surprisingly. NS is near the bottom of the list. Towards the end of the year, Nova Scotia’s chief medical officer, Dr. Robert Strang, made a statement where he wanted the provinces’ physicians to ween patients back from current prescribed levels of narcotics exceeding the 90 mg per day of morphine and to keep to max of 50 mg if possible. He also wants long-term fentanyl patients backed off this drug in an effort to fit in with upcoming guidelines. The Nova Scotia College of Physicians and Surgeons is endorsing the CDC guidelines for prescribing opioids.
Lately in the news on the west coast we had a story in the news of 13 overdose deaths in one day making emergency kits a necessity. Nova Scotia Pharmacists are now able to dispense rescue kits of naloxone for overdose and these kits are becoming more available as the awareness of the antidote and education spreads.
The CDC promotes the prescreening of patients to avoid addiction. Overdose concerns are more prevalent with those over 65 years of age, history of overdose, substance abuse disorder (including alcohol), history of depression, renal or hepatic impairment and sleep-disordered breathing. Any patient may be considered at risk for overdose if they combine opioids with benzodiazepines, on a longterm formulation or especially just starting this medication, on an opioid for longer than 3 months, or on more than 100 morphine mg equivalents. Addiction is more prevalent with this level of morphine equivalents as well as being on the opioid longer than 3 months.
Nova Scotia’s Dr. Mary Lynch has gone on the record as not being in favour with these strict guidelines and claims that there are many of her patients where there simply is no alternative drug for them. Many physicians are unclear as to what they are supposed to use to control the pain of their patients.
Unfortunately later this year we heard of a list of Doctors flagged by Ontario’s Ministry of health because they were prescribing the equivalent opioid dose of 150 Tylenol 3’s daily for some patients. 86 physicians were the target of this probe.
The recommendations include such non pharmacologic modalities as cognitive-behavioral therapy, exercise therapy, complimentary medicine (like yoga, meditation and acupuncture). Nonopioid analgesics recommended include acetaminophen, NSAIDS, Cox-2 inhibitors, anticonvulsants like gabapentin or pregabalin, and antidepressants like tricyclics and serotonin and norepinephrine reuptake inhibitors. Other therapies involve epidural injection and biofeedback.
With such a sense of urgency and recommendations of treatments not normally seen by physicians in general medicine, one would expect that physicians would be open to topical pain relief. In speaking to physicians I have found a friendly acceptance but a definite hesitance in writing for these compounds. These compounds are new to them and contain such familiar oral ingredients as ketamine, ketoprofen, clonidine, gabapentin, and lidocaine. They may also use lorazepam, carbamazepine, baclofen, cyclobenzaprine, dextromethorphan, and others. A recent article written by myself and a local palliative care doctor covers these ingredients. Check it out here.
This is a tremendous opportunity to reduce opioid use and improve pain relief. As I have seen from physicians that have tried this and seen it working in their patients, confidence comes with numbers and experience. The lack of side effects, interactions and lowered dose is something they like. Contact a compounding pharmacy and ask them more.
Should Pharmacists be blasted for selling what some call alternative therapies or products that are not “evidence based”? These criticisms can blindside unsuspecting Pharmacists trying to do what they can for their patients regardless of the fact that they are making a profit from it or not. What makes it more difficult is the way in which these criticisms are delivered, especially when delivered in an offensive type of online statement like most opinions are delivered today. It makes one grow thick skin if they wish to continue. As a pharmacist myself, I can reflect on the strong personal feelings we have towards our patients, especially in small community pharmacies. Not that many other health care professionals don’t have this deep feeling of ownership in their patient’s heath, it’s just that as pharmacists, the frequency we see these people is just so much higher, either in person or on the phone. We are one of the most if not the most accessible in their health care team and we answer a lot of questions from them, gladly.
Not only are we seeing these people regularly for health related concerns, but we also see them in passing when they need milk or a greeting card. In short, they feel and we feel like we see them more than some of our own family members sometimes. Couple this with the utter vastness of concerns this patient has and relies on us for.
Quite often these questions fall within the 80% of questions we hear every day. Prescription medications, interactions, side effects, screening what should go on to the doctor and what doesn’t need to, and OTC issues like supplements, cough and cold, pain relief, skin ailments, self treatable infections of all kinds, preventative measures, weight loss advice, and many more. During Med Review interviews, we uncover medical issues not being addressed fully or at all. There are medical issues that are treated in ways that the patient would prefer were treated a different way, either due to current side effects, potential side effects, interactions, or for the simple reason that they just want to be on fewer medications.
Now some may consider this an environment that sets up a scenario for a trap of giving the patient something that hasn’t been proven with studies of thousands and thousands of test subjects in randomized controlled trials. There has been no drug rep with glossy handouts showing graphs and impressive relative change overshadowing a less impressive absolute change in results. Perhaps the pharmacist has no idea of any studies that might exist for anything at their OTC disposal, no numbers needed to treat are at their fingertips (however unimpressive even Rx values for NNT are).
The truth is, a lot of these OTC treatments, even though we are taught them in Pharmacy school as recommended treatments, don’t have all that much in the way of studies to prove they work as I pointed out in a previous blog . This starts the slippery slope of evidence based to non evidence based medicine. This is a continuum rather than a conscious switch. As pharmacists who see the direct results of these recommendations daily, we begin to realize what the term “evidence based” means. It includes the evidence they see every day. Some refer only to large centre, many subject, randomized controlled trials for their definition of this term. Of course this is the basis of our scientific and medical knowledge and has extended lifespan many years. These people however may also recommend some things in what is known as off label use of some medications where the evidence is less plentiful. This is outlined in a recent blog: http://stonespharmasave.com/blog/?p=796 . The statistical method is a gift that helps us weed out chance encounters from truth (http://stonespharmasave.com/blog/?s=statistics ) . Anecdotal evidence can be notoriously prone to incorrect conclusions as it sidesteps statistics in its conclusions. Sometimes we just don’t have these studies available to us and must rely on smaller studies or a physiological basis for a recommendation.
I see this with topical pain compounding all the time. Repeated successful results with a scientific basis and numerous small studies and numerous anecdotal reports drive more recommendations and more feedback. This spreads to physicians that may be skeptical on how these products work. With one patient with a favourable results they become more comfortable in writing again. If a patient tries a prescription medication and it doesn’t work is the Doctor a quack? Of course not. Evidence based becomes what you see before you in your little world, regardless of what online bullies think, as long as your first priority is to keep the patient safe.
Graham MacKenzie Ph.C.
I had a conversation with our local palliative care and pain clinic doctor the other day. As a disclaimer, this physician is open to treating patients with the safety of the patient first in mind and he also has what I refer to as an “open mind” when it comes to doing whatever we can to alleviate pain and suffering. A lot of the time it involves using medications and therapies that most physicians would prescribe. It also involves therapies that are safe and effective but are shunned by other physicians either because of lack of knowledge or experience with them or because they claim it is an off label use or one that lacks either a firm recommendation from a governing body or has not been recommended at a recent conference they attended.
Off label prescription writing is certainly not a stranger to my daily dispensing of drugs. Some reviews put this practice as high as 10% of prescriptions written in Canada. A May 2012 MacLean’s article discusses this as a major issue and a huge gamble for the physicians writing these prescriptions. As a pharmacists, I can assure you that this practice is the norm and for the most part doesn’t land people in the hospital any more often than officially approved writing of any other prescription medication such as NSAIDS, narcotics, blood pressure or heart meds, or antibiotics, to name a few. There are hundreds of examples of off label uses of drugs now being written for. A few common ones listed by the Lexicomp Facts and Comparisons Off Label are:
ASA for high risk coronary artery disease
Clonidine for hot flashes
Erythromycin for acne vulgaris
Folic acid for neural tube defects
Gabapentin for diabetic neuropathy
Nifedipine topical for anal fissures
Trazodone for insomnia in the elderly
Amitriptyline (oral or topical) for neuropathic pain
Childhood and adolescent uses of many medications
Note the use of the amitriptyline topically. Topical compounds are notoriously listed here although there are studies showing they work for various types of pain when used correctly at the right strength. Granted many of these studies are small but many are well designed and like I always say, nothing beats the experience of the first patient a physician tries and sees the topical preparation working and the lack of side effects compared to oral medications is an added bonus.
Most consider topical pain therapy to be limited to capsaicin, lidocaine and camphor menthol combinations. There is an entire universe out there of other ingredients used in these preparations. And for those who like a few references here you go.
Dubinsky RM, Kabbani H, El-Chami Z, Boutwell C, Ali H; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: treatment of postherpetic neuralgia: an evidence-based report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2004;63(6):959-965.[PubMed 15452284]
Ho KY, Huh BK, White WD, Yeh CC, Miller EJ. Topical amitriptyline versus lidocaine in the treatment of neuropathic pain. Clin J Pain. 2008;24(1):51-55.[PubMed 18180637]
Lynch ME, Clark AJ, Sawynok J, Sullivan MJ. Topical 2% amitriptyline and 1% ketamine in neuropathic pain syndromes: a randomized, double-blind, placebo-controlled trial. Anesthesiology. 2005;103(1):140-146.[PubMed 15983466]
Lockhart E. Topical combination of amitriptyline and ketamine for post herpetic neuralgia. Poster presented at: American Pain Society Annual Meeting; May 6-9, 2004; Vancouver, BC. http://www.ampainsoc.org/db2/abstract/view?poster_id=2185#893. Accessed November 4, 2008.
Now a common complaint is that I supply studies that cherry pick what I am trying to prove, although I assume that whomever is asking has plenty of studies to favour something against my side. The point is, when you know something works, and it’s safe, you tend to care more about potential patients and less about converting non believers. Topical pain relief is just one of those “alternative” therapies. Many would consider off label use to be alternative therapy by definition. If alternative therapy is something that wanders past a monograph or official indication, then many practice alternative medicine. If that therapy is “recommended” by a medical group then for most it becomes accepted therapy and therefore not alternative. Although this may make them more comfortable with prescribing choices, alternative therapy’s definition is one that changes based on the one defining it.
You may be the last person to side with even listen to something that isn’t taught in Med School or Pharmacy School or in Nursing School or perhaps you are one to be weary about snake oil or getting hoodwinked on some “holistic scam”. As it turns out there is an established way of treating pain of all kinds. Personally I felt the same way before I started compounding. As a student I worked for a Compounding Pharmacy and was exposed to many aspects of individualized therapy. Ironically, none of that had anything to do with topical pain relief beyond menthol and camphor, although there were plenty of compounds for other health issues that helped countless patients in my time there as a student.
Luckily there is a Physician that is involved with palliative care and general pain clinic work that visited my Pharmacy when it was renovated with my compounding lab in plain view. It takes a physician like this to really result in patients receiving pain relief with a lack of systemic side effects that can burden long and short-term pain patients. These patients have a wide range of medical issues; cancer, arthritis, nerve pain, soft tissue pain, back pain, headache, fibromyalgia, lupus, pulled muscle, sprains, athletic injuries, and other types of pain that most always has been getting treated with conventional oral NSAIDS, Acetaminophen, and Narcotics in varying amounts, sometimes all at once. It is hard to picture even one of these moderate to severe pain patients that does not experience a side effect that is at the level of at least a nuisance and quite often more than that. Chronic constipation, nausea, sedation and GI ulceration/bleeding being the most common side effects we see. Added to this is the complication of drug-drug and drug-disease interactions that allow perhaps the patient to be on the drug but watchful for potential adverse reactions or periodic monitoring and follow up.
One thing I have realized as a Pharmacist is that nothing can replace clinical experience, especially when it comes to future recommendations to patients and Physicians. After years of doing this it has now become a go to recommendation for pain relief. This physician that originally began writing for these pain compounds wrote an article in Rehab and Community Care to help educate caregivers on the active pharmaceutical ingredients used with these compounds. I often educate physicians and patients on the benefits of these compounds. Without a doubt, one of the best contributions I have seen my pharmacy have towards the overall wellbeing of patients, even if it isn’t curing them of anything at all, just relieving a symptom.
| One of the body’s initial responses to stress is the release of hormones such cortisol that initially help a person to react or adapt to a stressful situation. High levels of cortisol can also lead to exacerbation of skin conditions such as psoriasis and eczema. We are here to help!
Treatments for eczema (atopic dermatitis) aim to control inflammation, decrease itching, and manage infections that may occur as a result of repeated skin irritation. Common treatments can cause significant side effects; for example, topical corticosteroids used to decrease inflammation and control itching may cause skin thinning and prolong the healing time of damaged skin, and topical tacrolimus can cause a burning sensation or itching.
Topical vitamin B12 offers a new therapeutic approach for eczema. A study showed that topical application of vitamin B12 cream (0.07% cyanocobalamin) reduced the severity and extent of eczema. Both physicians and study participants rated the vitamin B12 cream as significantly superior to the placebo cream, and the treatment was very well tolerated. Avocado oil has been added to improve the formulation so that vitamin B12 cream can be distributed more easily on the surface of the skin, or we can use a specialized base that is easily applied and cosmetically appealing.
For patients with localized psoriasis, and for many of those with moderate psoriasis as well, the mainstay of treatment is still topical therapy. Topical regimens, such as combination therapy with topical tacrolimus and salicylic acid, can be helpful. Vitamin B12 cream also has considerable potential as a well-tolerated, long-term topical therapy of psoriasis. Oral vitamin B12 is rapidly eliminated by the body, and oral vitamin B12 does not appear to be beneficial for psoriasis.
Methotrexate has been used orally as a treatment for psoriasis by dermatologists for over 30 years, but oral methotrexate can cause serious side effects. Interestingly, researchers from the Department of Dermatology, University of California-San Francisco, and three other locations note that if methotrexate is properly compounded into a topical gel and dosed appropriately, it can provide better results without the bad side effects. Furthermore, published data have indicated that 70% of patients prefer topical therapy for psoriasis. A placebo-controlled double-blind study evaluated methotrexate 0.25% gel applied topically to treat patients with psoriasis vulgaris. After four weeks, 83.3% of patients improved compared to 6.7% of patients who received a placebo. The treatment was well-tolerated by all the patients, with no adverse drug-related symptoms and no dropouts.
A new study has reported that children who take probiotics – “good” bacteria that normally live in our guts – are less likely to develop eczema. Researchers have found that infants on probiotic supplements were 50% less likely to develop eczema, and taking probiotic supplements daily could reduce the risk of eczema in older children by 58%. Study results vary, and one of the reasons is because different types of probiotics are used in various studies and produce different results. The best evidence for improvement of eczema is associated with the probiotic Lactobacillus rhamnosus GG. Lactobacillus rhamnosus GG supplements are available in powdered or chewable forms.
|British Journal of Dermatology 2004; 150: 977–983.
Arch Dermatol. 2005;141:43-46
J Cutan Med Surg 2001; 299-302
J Dermatol 2004 Oct;31(10):798-801
Int J Dermatol 2003 Feb;42(2):157-9
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