Evaluating the efficacy of vaginal dehydroepiandosterone for vaginal symptoms in postmenopausal cancer survivors: NCCTG N10C1 (Alliance).

BACKGROUND: Women with estrogen deficiencies can suffer from vaginal symptoms that negatively impact sexual health. This study evaluated vaginal dehydroepiandrosterone (DHEA) for alleviation of vaginal symptoms. METHODS: This three-arm randomized, controlled trial evaluated DHEA 3.25 mg and DHEA 6.5 mg, each compared to a plain moisturizer (PM) over 12 weeks, to improve the severity of vaginal dryness or dyspareunia, measured with an ordinal scale, and overall sexual health using the Female Sexual Function Index (FSFI). Postmenopausal women with a history of breast or gynecologic cancer who had completed primary treatment, had no evidence of disease, and reported at least moderate vaginal symptoms were eligible. The mean change from baseline to week 12 in the severity of vaginal dryness or dyspareunia for each DHEA dose was compared to PM and analyzed by two independent t tests using a Bonferroni correction. RESULTS: Four hundred sixty-four women were randomized. All arms reported improvement in either dryness or dyspareunia. Neither DHEA dose was statistically significantly different from PM at 12 weeks (6.25 mg, p = .08; 3.25 mg, p = 0.48), although a significant difference at 8 weeks for 6.5 mg DHEA was observed (p = 0.005). Women on the 6.5 mg arm of DHEA reported significantly better sexual health on the FSFI (p < 0.001). There were no significant differences in provider-graded toxicities and few significant differences in self-reported side effects. CONCLUSION: PM and DHEA improved vaginal symptoms at 12 weeks. However, vaginal DHEA, 6.5 mg, significantly improved sexual health. Vaginal DHEA warrants further investigation in women with a history of cancer.

Heartworm-, Flea-, and Tick-associated Diseases in Dogs: A Review of Common Parasites and Drug Classes Prophylactic Against Them.

Throughout recorded history, the canine-human connection has varied by custom, purpose, and intensity. In many cultures worldwide, dogs have long been considered essential workers, protectors and guardians, and, often, an integral part of the family unit. Ensuring the health and quality of life of those companion animals is essential to preserving the bond between dogs and their owners. Fortunately, advances in veterinary science continue to improve treatments and cures for and prophylaxis against a variety of deadly canine diseases, several of which can be sourced to ectoparasites or endoparasites. For many veterinary patients, a customized preparation often proves to be the best therapeutic option, but many compounding-pharmacy stores also include a retail component that offers ready access to manufactured prescription medications, including those prophylactic against canine flea, tick, or heartworm infestation. Because dog owners often need guidance in selecting such products and assistance with obtaining them, this article will be of special interest to ompounders in those pharmacies. To that end, the following content addresses common canine parasites and classes of drugs that prevent the illnesses they cause, with emphasis on heartworm disease.

Prophylaxis Against Heartworm Infection and Flea or Tick Infestation in Dogs: Single Agents and Combination-Drug Products.

From ancient times to the present, parasites and the diseases they transmit have jeopardized the health and wellbeing of working and companion canines worldwide. Many common pests that afflict dogs can be classified as ectoparasites (e.g., fleas, ticks, lice), which serve as vectors of pathogens transmitted as the organism feeds or defecates; or endoparasites (e. g, helminths, protozoa), which can cause slowly progressive subclinical canine diseases as well as acute illnesses associated with high morbidity and mortality rates. Safe, effective antiparasitic prophylaxis in dogs remains a topic of major interest to both veterinarians and their clients, especially with respect to the prevention of canine heartworm infection and flea or tick infestation. Many compounders, especially those whose pharmacy includes a retail component, counsel veterinarians and pet owners about preparations and commercially available medications that prevent or treat parasitic infestations and provide assistance in obtaining those therapies. To support such efforts, this article provides information about single agents and combination-drug products prophylactic against common canine parasites, emerging resistance to those medications, and the toxic effects that such treatments can engender in some canine breeds.

Compounding for the Treatment of COVID-19 and Long COVID, Part 2: Manifestations of Infection, Nomenclature, Transmission, and Treatment.

Described by some authors as a "black swan event . . . likened to the economic scene of World War Two," the effects of coronavirus-disease-2019 (COVID-19) and attempted techniques for its prevention and treatment have presented medical, economic, social, and (often) politicized challenges on a global scale. Caused by the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 is, in many patients, associated with severe morbidity and mortality during the first few weeks after infection. At the time of this writing, estimates indicate that up to 70% of survivors may also experience "long COVID," a condition that can persist for weeks, months, or years after virus-free status has been achieved, often produces severe symptoms across multiple organ systems, and can result in a wide variety of adverse outcomes. Scientific knowledge about COVID-19 and long COVID continues to evolve at a rate insufficient to address the protean manifestations and effects of continually emerging novel SARS-CoV-2 variants. When the recovery of afflicted patients is further challenged by intolerance to ingredients in (or available doses or dosage forms of) commercially manufactured medications that could provide therapeutic support, customized formulations may offer relief and enable healing. In this article, COVID-19 is addressed as an entity (i.e., the pandemic crisis it engendered is summarized to date, the most common signs and symptoms of that disease are described, and the phenomenon of cytokine storm in infected patients is examined), SARS-CoV-2 is discussed (i.e., common nomenclature systems used to describe and track that virus are presented and the processes of viral transmission, mechanisms of action, replication, and recombination are briefly reviewed), and the efficacy of a currently underappreciated agent (low-dose naltrexone) for the treatment of COVID-19 is considered. Two compounded formulations that can be used to treat the signs, symptoms, and/or sequelae of acute COVID-19 and/or long COVID are provided for easy reference.

Compounding for the Treatment of COVID-19 and Long COVID, Part 1: Terminology, Mutations, and Variants.

COVID-19 (coronavirus disease 2019), which is caused by the positive-stranded ribonucleic acid virus SARS-CoV-2 (acute respiratory syndrome coronavirus 2), is an extremely contagious airborne illness of pandemic proportions. In the modern era, few diseases other than COVID-19 have produced such severe, prolific, and protean short-term adverse effects and long-term sequelae. In addition, few other pandemics have exhibited a trajectory of morbidity and mortality so affected by social, economic, and political factors as well as individual personal perceptions and beliefs. Vaccines for the prevention of SARS-CoV-2 infection and treatments for COVID-19 mitigate associated morbidity and mortality, but an increasing array of variants presents challenges to therapeutic effectiveness. As a result, afflicted patients often require customized treatments that address the severity of their infection, the manifestations of disease they exhibit, and their individual pharmacogenomic profile. In such cases, a compounded preparation may offer needed support for recovery. This article, which is the first in a series on compounding for COVID-19 and long COVID (i.e., the long- term sequelae of SARS-CoV-2 infection), provides information about pertinent viral terminology and a brief overview of SARS-CoV-2 mutations and variants of note. Two formulations for customized compounds that may prove effective in treating the acute and/or long-term effects of COVID-19 when commercial therapies have failed are also provided.

Compounded "Monster Spray" for Nighttime Terrors: A Case Report.

Among the challenges most difficult to treat in the spectrum of pediatric anxieties are severe, persistent nighttime terrors (e.g., anticipating or "perceiving" the presence of monsters or other creatures under the bed or in the closet, nightmares) that disrupt a child's sleep, impact his or her overall adjustment, negatively affect the quality of family life, and may eventually require clinical assessment and intervention. This article describes a compounded preparation that has proven successful in combatting such fears and enabling the recovery of children so afflicted.

Compounding for the Treatment of COVID-19 and Long COVID, Part 4: The Legacy of Chronic COVID.

People infected by severe acute respiratory coronavirus 2 (SARS-CoV-2) risk the development of not only acute coronavirus- disease-2019 (COVID-19) - the signs and symptoms of which range from none to severe illness that requires intensive treatment - but also long COVID (i.e., chronic COVID), a cyclical, progressive, multiphasic illness characterized by myriad debilitating conditions that persist long term. In some patients, those sequelae result in psychiatric disorders that can lead to suicide or other forms of self-harm, incidences of which have increased exponentially since before the COVID pandemic. It has been suggested that long COVID develops in an estimated 10% to 35% of people diagnosed as having COVID-19. Because the success of therapy for either form of COVID can be complicated by each patient's pharmacogenomic profile, personal treatment preferences, medical needs, and/or dosing requirements, we have found that in some people so afflicted, manufactured medications are ineffective or intolerable, and that for those individuals, a customized compound often provides relief and promotes recovery. The primary focus of this article is long COVID. The pathogenesis of that disease is reviewed, therapies for the signs and symptoms it engenders are examined, and 2 compounded formulations effective in treating both acute and chronic COVID-19 are presented.

Compounding for the Treatment of COVID-19 and Long COVID, Part 5: Associated Conditions, Prophylaxis, and Effective Treatment.

The effects of infection with the highly transmissible severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the coronavirus- disease-2019 (COVID-19) it engenders continue to demonstrate that worldwide, the detection, prediction, and control of novel-pathogen pandemics remain largely unattained achievements. Key to successfully meeting those goals is a thorough understanding of the mechanisms of evolving causative agents and effective prophylaxis against them. In this article, we review common conditions that afflict people with COVID-19 or long COVID, examine the effectiveness of vaccines designed to prevent infection with SARS-CoV-2 and mitigate its sequelae, and provide formulations for 2 compounded preparations that can assist recovery from acute and chronic conditions caused by that virus when manufactured drugs are unavailable in required dosages or dosage forms or cannot be tolerated by the patient.

Compounding for the Treatment of COVID-19 and Long COVID, Part 3: The Role of Toll-like Receptors in SARS-CoV-2 Infection and COVID Development.

Toll-like receptors, which are type I transmembrane proteins and pattern recognition receptors found on cell surfaces and in intracellular membranes, serve as central mediators of both initial innate-immune responses and secondary adaptive/acquired-immune responses. Toll-like receptor 4, the activation of which leads to the synthesis of proinflammatory cytokines and chemokines, has been shown to have a vital role in the innate immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In our practice of pharmaceutical compounding, we noted that some individuals with coronavirus disease- 2019 (COVID-19) or long COVID achieved limited or no benefit from commercially manufactured treatments designed to alleviate symptoms and enable recovery. We suggest that in such cases, a compounded formulation, which can be easily customized to provide that support, may be of benefit. This article provides a brief review of the ways in which toll-like receptors in general, and toll-like receptor 4 in particular, affect the development and progression of SARS-CoV-2 infection and COVID-19, especially with respect to the human respiratory and central nervous systems and people rendered vulnerable by a comorbid condition (diabetes, obesity) or age. Instructions for compounding 2 customized preparations useful in the treatment of COVID-19 and long COVID are also provided.

A Compendium of Compounding Agents and Formulations, Part 3: Gentamicin Sulfate and Benzoyl Peroxide.

Since antiquity, the safety and effectiveness of topical and transdermal medications in treating a host of somatic conditions, including disorders that afflict the skin, have been appreciated. Those drug-delivery forms offer convenient self-administration; obviate gastrointestinal-tract absorption and hepatic-first-pass metabolism, thereby improving bioavailability and maintaining sufficient drug concentration within the therapeutic window; and facilitate the transmission of the largest fraction of drug molecules to the target area, thus maximizing therapeutic potential and reducing systemic drug toxicity. In this article, gentamicin and benzoyl peroxide, neither of which is commercially available currently in an easily modifiable topical or transdermal form, are profiled, and 2 compounded formulations are provided for easy reference.

A Compendium of Compounding Agents and Formulations, Part 2: Metronidazole, Misoprostol, and Phenytoin.

When compounded with synergistic ingredients, many pathogenicidal or anti-inflammatory drugs are particularly effective in resolving dermal or mucosal wounds that have proven refractory to treatment with standardized medications. In a customized preparation, such agents offer therapy that can be easily revised to repair injured tissues, minimize discomfort, and reduce morbidity. In this article, profiles of metronidazole, misoprostol, and phenytoin (drugs with often underappreciated wound-healing effects) are presented, and formulations designed to restore tissue integrity are provided for easy reference.

A Compendium of Compounding Agents and Formulations, Part 4: Nifedipine and Pentoxifylline.

The medical, economic, and social effects of painful chronic wounds such as anal fissures, which frequently prove refractory to treatment with commercially available medications, are often underestimated by clinicians. Those types of injuries, which afflicted individuals are often reluctant to discuss with healthcare providers, can lead to a greatly restricted lifestyle; result in depression, anxiety, social isolation, and embarrassment; require extended or repeated hospital stays; and create a financial burden for the patient and for society. Because interpatient variables can preclude the effectiveness of standardized mass-produced wound-healing products, a compounded formulation that can be formulated to include drugs proven effective in safe but off-label uses and that can be modified as patients' medical needs require may achieve the therapeutic goal. In this report, 2 such agents shown to promote wound healing are profiled: the vasodilator nifedipine, a first-generation calcium channel blocker that is used to treat hypertension and angina pectoris; and pentoxifylline, a synthetic dimethylxanthine derivative that facilitates vasodilation, improves erythrocyte flexibility, enhances blood flow, and reduces blood viscosity. Formulations that incorporate those drugs, which are underrecognized as effective healing agents when compounded as directed, are included for easy reference.

A Compendium of Compounding Agents and Formulations, Part 1: Melatonin.

The lipophilic hormone melatonin is widely known as a sleep-inducing agent, but its dermal-healing effects remain underappreciated. Although numerous commercially manufactured products are prescribed to heal and protect the human skin, not all are effective, and not all patients can tolerate the combinations of drugs and excipients in those treatments (some of which, such as corticosteroids, produce adverse effects). In addition, required active ingredients may not be available in the doses or dosage forms needed. In such cases, a compounded preparation may provide an effective alternative, but finding formulations and information about which pharmaceuticals to compound as a sole treatment or in combination with other ingredients can require extensive research. To assist that effort, this series provides - in a quick-reference format - profiles of agents that can be effectively used in compounding and formulations that contain them. In this article, information about the healing and prophylactic effects of melatonin in various forms is presented, and 2 formulations for melatonin-containing compounds are provided.

A Compendium of Compounding Agents and Formulations, Part 5: Timolol and Beta-glucans.

Cutaneous wounds that prove refractory to treatment with commercially manufactured medications impose a burden on patients, create challenges for the clinicians who treat them, and increase the cost of therapy. The success of pharmaceutical wound management and cure depends in part on the degree to which active healing agents are delivered quickly and effectively to injured tissues (factors also affected by the drug[s] and excipients incorporated and skin permeability at the injured site). When an external injury has failed to resolve despite treatment with standardized drug products, a pharmaceutical compound can often provide healing relief. In this report, profiles of and formulations containing timolol (a beta- adrenergic receptor antagonist) and beta-glucans (glucose polymers) are provided. The healing effects of those agents are underrecognized in mainstream medicine, and as a result, they remain underprescribed and unavailable in commercial medications. However, when included in a customized pharmaceutical compound, they can enable and accelerate dermal- wound resolution.

A Compendium of Compounding Agents and Formulations, Part 6: Additional Preparations for Refractory Dermal-wound Healing.

Skin injuries, whether acute or chronic, can present therapeutic challenges engendered by wound type and etiology as well as the pharmacogenomic profile and treatment preferences of the patient. As a result, standardized manufactured medications may fail to promote healing or their use may prove intolerable (complications that impose a burden on patients and ultimately on the society in which they live and the healthcare system that supports them). For cases in which commercially available wound-healing products fail or cannot be used, a uniquely formulated pharmaceutical compound may be effective. In this article, the differences between acute and chronic dermal injuries are presented, wound infection is discussed, specific compounds designed to treatment some of the most challenging dermal-wound types are listed, and two complete formulations that have also proven safe and effective in promoting the healing of external skin damage are provided.

A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a troublesome chronic symptom that has no proven pharmacologic treatment. The purpose of this double-blind randomized placebo-controlled trial was to evaluate a novel compounded topical gel for this problem. METHODS: Patients with CIPN were randomized to baclofen 10 mg, amitriptyline HCL 40 mg, and ketamine 20 mg in a pluronic lecithin organogel (BAK-PLO) versus placebo (PLO) to determine its effect on numbness, tingling, pain, and function. The primary endpoint was the baseline-adjusted sensory subscale of the EORTC QLQ-CIPN20, at 4 weeks. RESULTS: Data in 208 patients reveal a trend for improvement that is greater in the BAK-PLO arm over placebo in both the sensory (p = 0.053) and motor subscales (p = 0.021). The greatest improvements were related to the symptoms of tingling, cramping, and shooting/burning pain in the hands as well as difficulty in holding a pen. There were no undesirable toxicities associated with the BAK-PLO and no evidence of systemic toxicity. CONCLUSION: Topical treatment with BAK-PLO appears to somewhat improve symptoms of CIPN. This topical gel was well tolerated, without evident systemic toxicity. Further research is needed with increased doses to better clarify the clinical role of this treatment in CIPN.

Compounding Pearls -- Wound Care: Drugs and Formulations for Dermal Healing, Part 2.

Diseases of and injuries to the human skin have been recognized since antiquity as health hazards that can increase morbidity and mortality and greatly compromise quality of life. The earliest effective treatments for such conditions and disorders were compounded, as were all ancient medicaments, to accommodate individual patient sensitivities and responses to therapy. That tradition continues today in precision pharmaceutical compounding, which is an essential component in a triad of medical and pharmaceutical care that actively involves physicians, pharmacists, and patients. To ensure a good therapeutic outcome, compounders must be acutely aware of drug compatibilities and adverse interactions. Those topics are addressed in this second article in a series on agents that, when effectively compounded, promote dermal healing when conventional therapies fail to do so or cannot be tolerated by the patient. Misoprostol, gabapentin, ketamine, and aloe vera are described in that regard. Formulations that are, at the time of this writing, unavailable in the literature are also provided.

Compounding Pearls -- Wound Care: Drugs and Formulations for Dermal Healing.

Healthy human skin performs a constellation of functions essential to good health, and the consequences of disruption to that effective external defense system have been recognized since antiquity. The earliest treatments for dermal injuries and diseases were compounded: They were prepared for each patient and could be modified to address progressive phases of healing. The benefits of that therapeutic approach continue today, made immeasurably more effective by modern pharmaceutical compounding. In this article, which is the first of several in a series that presents healing-drug profiles, various agents that can be compounded to enable dermal healing are described. Those drugs are not commercially available in the most safe and effective combinations at the time of this writing, but a skilled compounding pharmacist can incorporate compatible agents in preparations designed to ensure best outcomes. Formulations that promote dermal healing are provided for easy reference.

Compounding Pearls--Wound Care: Drugs and Formulations for Dermal Healing, Part 3: The Roles of Nitric Oxide, Sildenafil, and Naltrexone.

Dermal healing occurs via a linear sequence of events in which growth factors cause cell proliferation and a subsequent integration of changes that involve soluble mediators, parenchymal and blood cells, and the production of extracellular matrix. Myriad factors influence the process and progress of healing damaged skin, and numerous agents have been used alone or in combination with other active substances to enable both responses to skin injury or disease. In this third article in a series on compounding for dermal healing, the role of nitric oxide in dermal repair is examined, as is the effectiveness of both sildenafil and naltrexone in promoting recovery. Also provided are compounded skin-healing formulations that proved effective when treatment with commercially manufactured medications failed.

Compounding Pearls -- Wound Care: Drugs and Formulations for Dermal Healing, Part 4. Insulin.

The doses, dosage forms, and compositions of pharmaceutical compounds are as numerous and varied as the conditions for which they are prescribed. Although many patients in the U.S. have access to standardized medications that are effective, people who experience adverse effects from preservatives, dyes, or fillers; rely on nonstandard chemotherapy protocols; or must be treated with atypical routes of therapy often benefit from medicines designed to meet their specific medical needs and personal preferences. Among the conditions that often prove refractory to standardized therapies are dermal injuries, which, if inadequately or inappropriately treated, can severely compromise overall health and well-being. In this article, the use of insulin to treat such lesions, especially in diabetic patients, is discussed, and a formulation for a topical compounded preparation containing that agent is provided.