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Tag 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.
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.
There are few medical issues that bring about a “must deal with” mentality than pain. Acute or chronic, it can have various causes: nerve pain, muscle pain, trauma, cancer, visceral, bone, various organ pain…it can be described as shooting, stabbing, dull, throbbing, aching, excruciating, and debilitating. Whatever the cause or description, when you have it you want it gone.