THE PCCA BLOG

Potential Options for Migraine Patients

Wed, 12 Jun 2024 14:54:28 GMT

June is National Migraine and Headache Awareness Month and we want you to be well equipped to care for your migraine and headache patients.

by Catherine Henderson, PharmD, PCCA Clinical Compounding Pharmacist

Migraines affect roughly 14-15% of people globally each year and is just one of more than 200 headache disorders.¹ If you’ve ever been a migraine patient or treated a migraine patient, you know how challenging it can be to find the right treatment for acute migraines and the best prophylaxis for chronic migraines.

Acute Migraines

The current standard of care for acute migraine involves use of NSAIDs, ergotamine derivatives, triptans, gepants and ditans. Combination therapy with antiemetics and/or caffeine is also a mainstay of treatment.² With the loss of isometheptene from the market, many compounders have been searching for a replacement. Since there are so few options for treating migraines, losing an agent that is effective for some patients leaves a gap that can be difficult to fill.

In the PCCA Clinical Services department, we have recently helped many members find an alternative option for patients who were previously using isometheptene. The way that isometheptene is thought to work is by constricting the cranial arteries. Caffeine is another cranial vasoconstrictor, often used in migraine headache formulations.³For patients who were previously experiencing relief with isometheptene, caffeine would be a reasonable inclusion in their formula.

One of my favorite formulas to recommend for acute migraine is piroxicam 40 mg/ondansetron 2 mg/caffeine troches. The combination of ingredients treats pain and nausea associated with migraine headaches and may provide faster relief due to the route of administration. As an anhydrous formula, both compounders and patients can benefit from the potential of longer beyond-use dates (BUDs).*

Another unique compounding option for acute migraine is intranasal lidocaine, which has been shown to decrease pain intensity and the need for rescue medications. It has been used in varying concentrations of 4-10% in each nostril. The benefit of this formula is that it provides a non-oral, non-injectable route of administration that can be useful in patients experiencing significant nausea. Combining lidocaine with ketorolac in a nasal spray is another option that has been studied and found to have even greater pain relief than lidocaine alone.⁴ Before choosing this combination, it is important to remember that the use of ketorolac is limited to five days, regardless of route of administration. Evaluating the number of headache days per month that a patient has can help determine if this is an appropriate treatment.⁵

Migraine Prophylaxis

While the goals of therapy for acute migraine are to relieve symptoms as quickly as possible — with as few side effects as possible — we also need to avoid medication overuse headaches (a headache that results from the frequent use of acute medicines or painkillers).⁶ In any migraine patient, prevention is an important piece of the puzzle. Current migraine prophylaxis medications include beta-blockers (propranolol), anticonvulsants (valproate, topiramate), antidepressants (amitriptyline) and calcitonin gene-related peptide receptors (CGRPs) (erenumab).⁷ These prophylactic medications have varying success rates, with the new class of CGRPs having the greatest efficacy.⁸ Unfortunately, all of these medications come with the risk of adverse events and some come with a significant financial burden.

Alpha-lipoic acid and riboflavin are two agents that have been shown to help with migraine prophylaxis. A study found that a dose of riboflavin 400 mg/day for three months reduced headache days, as well as the duration, frequency and pain score of migraine attacks.⁹ Another study found similar results with alpha-lipoic acid 300 mg twice daily for 12 weeks.¹⁰ Alpha-lipoic acid has also been studied as a preventative agent in adolescents.¹¹A benefit of these two agents is that they are generally well-tolerated and may be less expensive than other options. These agents can be used alone or as an adjunct to other prophylactic measures.

Treatment Success

In helping your patients navigate migraine treatment and prophylactic options, there are some key strategies and counseling points to consider. Many patients expect full resolution of their migraine symptoms and frequency and may give up on a treatment option too soon if those expectations aren’t managed. Most prophylactic measures must be taken daily for at least two months before a determination can be made about the success of the treatment. Encourage patients to keep a headache diary to collect data about their headache days, severity and other details related to their migraines.⁶

As pharmacists, we are also uniquely placed to screen for potential medication overuse. Medication overuse headaches are typically seen in patients with 15 or more headache days per month. Most migraine prophylactics won’t be effective in these patients until they go through a detox period from acute migraine treatments.¹²The most effective detox programs for medication overuse headaches include complete withdrawal from acute treatments and initiation of preventative medications.^13,14

You have the opportunity to make a significant impact on the lives of your patients who suffer with debilitating headache disorders. This article covered just a few of the creative ways that compounding pharmacists are contributing to solutions for migraines.

PCCA members with clinical services access may contact our Clinical Services team for help when compounding for patients with migraines and other compounding concerns.

*USP 795 establishes BUD limits by type of preparation in the absence of a USP−NF Compounded Preparation Monograph or CNSP-specific stability information.

References

Steiner, T. J., & Stovner, L. J. (2023). Global epidemiology of migraine and its implications for public health and health policy. Nature reviews. Neurology, 19(2), 109–117. Accessed May 2024 at https://doi.org/10.1038/s41582-022-00763-1
Ailani, J., Burch, R. C., & Robbins, M. S. (2021). The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache: The Journal of Head and Face Pain, 61(7), 1021–1039. Accessed May 2024 https://doi.org/10.1111/head.14153
Drugs.com (Last updated June 2023). Isometheptene, Caffeine, and Acetaminophen Tablets. Accessed May 2024 at https://www.drugs.com/pro/isometheptene-caffeine-and-acetaminophen-tablets.html
Chi, P. W., Hsieh, K. Y., Chen, K. Y., et al. (2019). Intranasal lidocaine for acute migraine: A meta-analysis of randomized controlled trials. PloS one, 14(10), e0224285. Accessed May 2024 at https://doi.org/10.1371/journal.pone.0224285
Pfaffenrath, V., Fenzl, E., Bregman, D., et al. (2012). Intranasal ketorolac tromethamine (SPRIX®) containing 6% of lidocaine (ROX-828) for acute treatment of migraine: Safety and efficacy data from a phase II clinical trial. Cephalalgia, 32(10), 766–777. Accessed May 2024 at https://doi.org/10.1177/0333102412451359
The Migraine Trust. (2021). Medication overuse headache. Accessed May 2024 at https://migrainetrust.org/understand-migraine/types-of-migraine/medication-overuse-headache/
Kumar, A., & Kadian, R. (2020). Migraine Prophylaxis. PubMed; StatPearls Publishing. Accessed May 2024 at https://www.ncbi.nlm.nih.gov/books/NBK507873/
Lampl, C., MaassenVanDenBrink, A., Deligianni, C.I. et al. The comparative effectiveness of migraine preventive drugs: a systematic review and network meta-analysis. J Headache Pain 24, 56 (2023). Accessed May 2024 at https://doi.org/10.1186/s10194-023-01594-1
Chen, Y.-S., Lee, H.-F., Tsai, C.-H., et al. (2021). Effect of Vitamin B2 supplementation on migraine prophylaxis: a systematic review and meta-analysis. Nutritional Neuroscience, 1–12. Accessed May 2024 at https://doi.org/10.1080/1028415X.2021.1904542
Kelishadi, M.R., Naeini, A.A., Khorvash, F. et al. The beneficial effect of Alpha-lipoic acid supplementation as a potential adjunct treatment in episodic migraines. Sci Rep 12, 271 (2022). Accessed May 2024 at https://doi.org/10.1038/s41598-021-04397-z
Puliappadamb, H. M., Satpathy, A. K., Mishra, et al. (2023). Evaluation of Safety and Efficacy of Add-on Alpha-Lipoic Acid on Migraine Prophylaxis in an Adolescent Population: A Randomized Controlled Trial. Journal of clinical pharmacology, 63(12), 1398–1407. Accessed May 2024 at https://doi.org/10.1002/jcph.2331
D'Amico, D., & Tepper, S. J. (2008). Prophylaxis of migraine: general principles and patient acceptance. Neuropsychiatric disease and treatment, 4(6), 1155–1167. Accessed May 2024 at https://doi.org/10.2147/ndt.s3497
Carlsen, L. N., Munksgaard, S. B., Jensen, R. H. et al. (2018). Complete detoxification is the most effective treatment of medication-overuse headache: A randomized controlled open-label trial. Cephalalgia : an international journal of headache, 38(2), 225–236. Accessed May 2024 at https://doi.org/10.1177/0333102417737779
Nielsen, M., Carlsen, L. N., Munksgaard, S. B., et al. (2019). Complete withdrawal is the most effective approach to reduce disability in patients with medication-overuse headache: A randomized controlled open-label trial. Cephalalgia, 39(7), 863–872. Accessed May 2024 at https://doi.org/10.1177/0333102419828994

These statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care or encourage its abandonment.

What the Proposed USP <795> Revisions Mean for BUDs

Mon, 12 Nov 2018 16:45:00 GMT

By Dylan Herr, Eagle Business Development Specialist

The content below was based on an earlier proposed version of USP General Chapter 795. However, USP has since released a newer version of the chapter. To see our most current content about the new version of the chapter, please read our blog post Proposed Changes to USP 795. "

On March 30, 2018, the Compounding Expert Committee of the United States Pharmacopeial Convention published proposed revisions to USP chapter <795> Pharmaceutical Compounding – Nonsterile Preparations. The revised chapter was open to public comments until July 31, 2018, and is expected to become official on December 1, 2019. Major revisions to the chapter include, but are not limited to, the following:

Removal of information specific to the handling of hazardous drugs; compounders were instructed to refer to USP chapter <800> Hazardous Drugs – Handling in Healthcare Settings
Addition of specific guidelines related to requirements for personnel training, evaluation, qualification, hygiene and garbing
Addition of minimum frequencies for cleaning and sanitizing nonsterile compounding areas and equipment
Removal of categories for nonsterile preparations based on the complexity of compounding processes
Addition of specific guidelines on complaint handling and adverse event reporting
Changes to the allowable beyond-use date (BUD) in the absence of stability information for nonaqueous dosage forms and for preserved aqueous dosage forms
Expansion of requirements for assigning BUDs for compounded preparations in the absence of stability information¹

Assigning BUDs

Of the proposed revisions, the expansion of requirements for assigning BUDs in the absence of stability information has the most potential to affect the way that compounders practice pharmacy. The current USP chapter <795> only requires that “when assigning a BUD, compounders shall consult and apply drug-specific and general stability documentation and literature when available.”² To meet this requirement, many compounding pharmacies use peer-reviewed journal articles and other literature references in order to provide a scientific justification for extended BUDs.

The revised chapter, however, states that BUDs may be extended past the maximum BUD by type of preparation in the absence of CNSP-specific stability information (as outlined in Table 3) “if there is a stability study (published or unpublished) using a stability-indicating assay for the specific API, CNSP (compounded nonsterile preparation), and container-closure that will be used.”¹ The inclusion of these requirements will make finding peer-reviewed journal articles and other literature references more challenging, as many of them are not formulation or container-closure specific.

Stability-Indicating Methods
Additionally, the revised chapter requires the use of a stability-indicating assay for stability studies. Historically, many compounding pharmacies have collected data to support extended BUDs for their formulations by having a contract analytical laboratory test the potency of the preparation at certain time-point intervals over the proposed BUD. This type of potency-over-time testing, however, does not meet the requirements of a stability study and of the revised USP <795> chapter, as it is not conducted using a stability-indicating assay to measure the potency of the active ingredient(s). While all stability-indicating assays measure the potency of an active ingredient, not all potency testing methods are stability-indicating.

One of the primary differences between a potency test and a stability study comes down to the analytical testing method used. While a potency testing method is reliable at quantitatively determining the concentration of a drug in a preparation at the time of compounding, not all potency testing methods are capable of separating the intact drug from its degradation products. As a result, these other substances could potentially mask or simulate the analytical behavior of the intact drug, resulting in an inaccurate concentration of the active ingredient. Results from this type of testing cannot be interpreted to determine that the product is stable over time, as there may have been degradant products or changes in the concentration of the active drug that were present, but not detected.

As a comparison, a stability-indicating assay is a potency testing method that is specifically developed and validated to differentiate between the active ingredient and the presence of other substances, such as impurities, degradation products and excipients. A stability-indicating assay is typically developed by forcibly degrading the compounded preparation through exposure to conditions known to produce decomposition, such as light, heat, oxidation, acids and bases. The stability-indicating assay is then validated in the presence of the resulting degradation products, which provides assurance that any increases or decreases in the active ingredient represent actual changes in the concentration of the drug.

Conclusion
All of this means that the requirements for extending the BUDs of nonsterile compounded preparations will likely become more stringent on December 1, 2019. We recommend that compounding pharmacies start developing strategies for establishing extended BUDs for their preparations now so as not to interrupt patient access to compounded medications.

PCCA has already invested the resources in their FormulaPlus™ program to provide members access to formulations with extended BUDs that have undergone testing using stability-indicating assays. PCCA members can access the complete list of FormulaPlus formulations here.

Furthermore, at Eagle, not only can we develop, validate and execute stability-indicating assays for most sterile and nonsterile compounded preparations, but we also offer consulting services on all aspects of testing and regulatory compliance. If you have questions about any of these matters, please contact us at 800.745.8916.

A version of this article was originally published the Summer 2018 issue of the Apothagram, PCCA’s quarterly, members-only magazine.

References
1. United States Pharmacopeial Convention. (2018). <795> pharmaceutical compounding –Nonsterile preparations [In-process revision: General chapters]. Pharmacopeial Forum, 44(3). Retrieved from http://www.usppf.com/pf/pub/
2. United States Pharmacopeial Convention. (2017). <795> pharmaceutical compounding –Nonsterile preparations. In United States pharmacopeia and national formulary (USP 41st ed. & NF 36th ed.). Rockville, MD: United States Pharmacopeial Convention, Inc.

PCCA Compounding Technician of the Month: November 2018

Wed, 07 Nov 2018 16:22:00 GMT

PCCA Compounding Technician of the Month:
November 2018

Suzette Holzer, CPhT
Of Heartland Apothecary Compounding and Infusion Pharmacy in Knoxville, Tennessee

Years in Compounding: 14

Path to Compounding: I didn’t start out in pharmacy, but I did start out in health care. I worked as a diagnostic medical sonographer for eleven years. An opportunity presented itself in 2004 to work at a compounding pharmacy helping to manage the hormone patients. Within months, I become a certified technician and went to PCCA for primary and aseptic training.

I enjoy that pharmacy compounding aims to create a solution to meet everyone’s specific needs. I have been told that compounding has saved marriages and that we have helped improve day-to-day activities for autistic children. We have created formulas and treatments for monkeys, horses, birds and tigers. I love the art of compounding because it is so creative, and you can help treat a different issue every day.

Favorite Formula:
PCCA Formula #6620 – Size #1 Capsules (PCCA members can access the formula here.)
T4/T3 formulas are my favorite. Thyroid needs hit very close to home to me as a thyroid cancer survivor. I like these formulas because each one is compounded for the individual’s specific needs based on lab work and symptoms they’ve shared with their health care provider. Being able to help people who have issues in this area makes this career even more rewarding and each calculated formula that much more important.

PCCA provides premade T3 dilutions and T4 dilutions. Members can find a similar formula that uses them here.

Success Story: This is a personal story that has been shared with me, and I was given permission to pass it on: A patient and friend was struggling eight years ago in many areas. She was overweight, was on nine different medications, and had to use a CPAP machine to sleep.

She came to the pharmacy looking for guidance, and we directed her toward a health care provider who would prescribe compounded medications. Her provider prescribed bioidentical hormones and magnesium glycinate to help with her sleep. Along with exercise and supplements, she has lost 80 lbs, and her health has drastically improved. She is no longer on multiple commercial drugs and overall feels she has a better quality of life. She always tells us how she is forever grateful for the way compounding and our pharmacy has changed her life.

Advice for New Compounders:
I would encourage those starting out in compounding to be as involved with their patients’ lives as possible. Make connections and build relationships with them so that you are better able to meet their individual needs. Always go above and beyond with customer service because word of mouth is your best compounding educator.

Lastly, I would encourage them to compound a high-quality product above all else. You are only as good as that last compound dispensed. This is not a job to be taken lightly, and people’s lives are changed because of the tailored work you do for them.

The views and therapies expressed in the above article are those of the interviewee and may not be endorsed by PCCA. The statements are provided for educational purposes only. They have not been evaluated by the Food and Drug Administration, and are not to be interpreted as a promise, guarantee or claim of therapeutic efficacy or safety. The information contained herein is not intended to replace or substitute for conventional medical care, or encourage its abandonment. Every patient is unique, and formulas should be adjusted to meet their individual needs.

Heartland Apothecary Compounding and Infusion Pharmacy is owned by Charles Wall, PharmD.

PCCA Compounding Pharmacist of the Month: November 2018

Mon, 05 Nov 2018 18:45:00 GMT

PCCA Compounding Pharmacist of the Month:
November 2018

Erik Nelson, PharmD
Of Sixth Avenue Medical Pharmacy in Spokane, Washington

Years in Compounding: 8

Path to Compounding: I wanted to do something in the medical field but couldn’t stand needles or the site of blood, so pharmacy was the most logical choice. Fast forward to now: We offer immunizations and autologous eye drops (serum tears), which involve both, so I guess you could say my comfort level has changed. But looking back, I wouldn’t have changed anything.

I first learned about compounding when I started working as an intern at Sixth Avenue Medical Pharmacy. I instantly gravitated toward it because compounding was an incredibly powerful way to connect with patients and help them achieve optimal health. It is truly the foundation of personalized medicine, and while the industry is facing challenges, it is here to stay. The results that patients get speak for themselves.

Favorite Formulas:
PCCA Formula #12674 – Topical Gel in PCCA Atrevis Hydrogel® (This formula has a FormulaPlus™ extended beyond-use date study in a bracketed concentration range. PCCA members can access the formula and the BUD study here.)
Many of our patients have had better outcomes with this.

PCCA Formula #11701 – Topical Cream in PCCA Clarifying™ (PCCA members can access the formula here.)
This is a nice compound that has been helpful for patients with acne.

Success Stories: We had a patient who wasn’t getting the results he needed with a commercial testosterone gel. He had also spent close to $9,000 out of pocket in just over a year. We talked to his doctor, who wrote the patient a prescription for testosterone in Atrevis Hydrogel. Both the patient and doctor were beyond pleased. The patient had his levels improve, and he saved a ton of money as well.

Advice for New Compounders: Immerse yourself in as much education as possible and always stay hungry for knowledge. Anyone who thinks they know it all or has seen everything there is to see is crazy.

Surround yourself with good people, friends, co-workers, colleagues, etc., and network, network, network. I have made some incredible friends from PCCA and A4M meetings that I constantly bounce ideas off of. Two heads are always better than one.

Sixth Avenue Medical Pharmacy is owned by Erik Nelson, PharmD.

PCCA Compounding Technician of the Month: October 2018

Tue, 16 Oct 2018 19:01:00 GMT

PCCA Compounding Technician of the Month:

October 2018

Christine Gaglia, Pharmacy Tech

Of Pine Pharmacy in Williamsville, New York

Years in Compounding: 6

Path to Compounding: I had relocated with my husband to Williamsville from Syracuse, New York. I had two small boys and met another mom at their school. She wanted to split a full-time job at a pharmacy. After researching the position, I found that it had perfect hours for a busy mother. I wanted to get away from the long hours in retail.

Seeing as it has worked out well for the last six years, I know I have found the perfect fit. I truly believe things happen for a reason, and I am very fortunate to find such a gratifying position at Pine Pharmacy.

I really like the idea of helping people with medicine that has to be custom made just for them. Mothers with children who have severe allergies depend on us to make their prescriptions correctly. Women who go through such highs and lows with menopause or cancer need something specific that we can custom make just for their bodies. It is truly a pleasure when they call with such gratitude.

Favorite Formula:

PCCA Formula #0821 – Troches in PCCA’s Gelatin Base (PCCA members can access the formula here.)

We have one patient who really enjoys these troches. She has to have different flavors and colors to distinguish each medicine. It really is interesting when making this formula how you can customize the color, taste and strength.

Success Story: There was a 5-year-old patient who was refusing to take his medicine. Another compounding pharmacy had made it, and he did not like the grape or cherry flavoring. We talked to the patient’s mother and offered the option of bubblegum flavor, and she thought he would try it. Not long after, she called for a refill, stating this medication was a godsend and that he loved it.

I had the opportunity to be there when they picked up the refill, and I said to him, “Hi, it is nice to meet you. I made your medicine for you.” He had the biggest smile and said, “Thank you. I really like it, and you did a great job!”

That is the compliment that means the most to me. There may not be frequent compliments, but you learn that those are the ones that can make your day.

Advice for New Compounders: I would let new compounders know that the prescriptions they are making are special for each customer. They need to take extra care when mixing, measuring and dispensing because this is not something taken off a shelf but something that is specific to each individual customer. With that comes the responsibility to make someone’s life a little easier.

Pine Pharmacy is owned by Al Muto, RPh.