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Thank you for entrusting in the compounding services at MD Custom Rx to help meet the unique medication needs of your patients. We are excited to share with you our monthly newsletter and look forward to continuing to be your medication problem solvers. Please don't ever hesitate to let us know how we can be of further assistance to you and your practice.
Sincerely,
John, Dan and Monica |
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PREVENTION AND TREATMENT OF
CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY
Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting side effect associated with several commonly used chemotherapeutic agents, including platinum agents, taxanes, vinca alkaloids, thalidomide, bortezomib, and ixabepilone. CIPN commonly occurs in 30-40% of patients. The degree of neuronal damage depends on many factors, including the chemotherapeutic agent, duration of therapy, cumulative dose, and concomitant use of other neurotoxic agents. Overall, CIPN can be extremely disabling and can negatively impact functional ability and quality of life. Therefore, it would be ideal to prevent CIPN before it occurs. However, given that many patients already have CIPN, finding effective treatment for established CIPN is also very important. The degree of neuronal damage depends on many factors, including the chemotherapeutic agent, duration of therapy, cumulative dose, and concomitant use of other neurotoxic agents.
N-ACETYLCYSTEINE /GLUTATHIONE
N-acetylcysteine is a precursor for the formation of glutathione. A pilot trial was carried out to investigate the efficacy of N-acetylcysteine in preventing CIPN. Fourteen patients with stage III colon cancer who were receiving adjuvant biweekly oxaliplatin plus weekly fluorouracil boluses and low-dose leucovorin were randomized to receive oral N-acetylcysteine (1,200 mg) or placebo. Patients in the treatment group had significantly less neuropathy after 8 and 12 cycles. Although this was a small trial, these data further support the hypothesis that glutathione is helpful in preventing CIPN.
GLUTAMINE
Glutamine, an amino acid that is involved in cellular energy and nitrogen donation, is hypothesized to have a neuroprotective effect. Two clinical trials have been conducted to assess the efficacy of oral glutamine in preventing paclitaxel-induced peripheral neuropathy. Both trials reported that patients who received glutamine had fewer neurotoxic symptoms than controls. However, both trials were small, each involving fewer than 20 patients treated with glutamine. Another trial was conducted to evaluate the efficacy of glutamine in preventing CIPN in patients treated with oxaliplatin. This trial involved 86 patients randomized to either receive or not receive glutamine (no placebo control); the finding was that patients who received glutamine had less peripheral neuropathy. In addition, glutamine did not appear to interfere with the efficacy of the chemotherapy. Larger, randomized, placebo-controlled trials are needed to verify these results.
TOPICAL AMITRIPTYLINE, KETAMINE +/− BACLOFEN
Topical therapies have been studied for the treatment of neuropathic pain. Preliminary studies demonstrated that topical amitriptyline with ketamine might be useful in the treatment of diabetic neuropathy, postsurgical and posttraumatic pain, hyperalgesia, and postherpetic neuralgia. No significant systemic absorption or toxicity was associated with topical application; this potentially offers an advantage over oral preparations, particularly in a patient population prone to polypharmacy and systemic toxicity. Based on these positive preliminary data, a double-blind, placebo-controlled trial was carried out to compare a topical gel (made of baclofen 10 mg, amitriptyline HCL 40 mg, and ketamine 20 mg in a pluronic lecithin organogel (BAK-PLO)) vs. placebo for the treatment of CIPN. These three agents were chosen because they have different and complementary mechanisms of action. Baclofen acts as a GABA receptor agonist, amitriptyline HCL affects both sodium channels and adenosine A receptors, and ketamine inhibits N-methyl-D-aspartate receptors. The trial involved 208 patients. The treatment group showed a greater improvement in the sensory scale as compared with the placebo group, the greatest of these improvements being in reducing tingling, cramping, and shooting/burning pain in the hands. The BAK-PLO group also showed an improvement in motor subscales. There were no apparent toxicities with the BAK-PLO treatment. Although the results of this trial were encouraging, further investigation of these topical agents in the treatment of CIPN is needed. Such investigation could focus on different dosing regimens and higher doses, given that the BAK-PLO treatment was well tolerated.
We can compound medications in the most appropriate dose and dosage form for the desired route of administration.
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EFFECTS OF PERCUTANEOUS ESTRADIOL-ORAL PROGESTERONE VERSUS ORAL CONJUGATED EQUINE ESTROGENS-MEDROXYPROGESTERONE ACETATE ON BREAST CELL PROLIFERATION
The ultimate goal of combined hormone therapy (HT) is to define treatment regimens and alternatives for postmenopausal women that provide effective relief from climacteric symptoms with minimal adverse effects on healthy epithelium such as the breast. HT has been associated with an increased risk for breast cancer in postmenopausal women. Various preparations, doses and regimens of HT can have different effects: combined estrogen-progestogen therapy confers a greater increase in breast cancer risk than estrogen monotherapy, and there is evidence to suggest that topical rather than systemic use of HT may lessen the increase in risk. Although the effects of added progestogens are not uniform, breast cell proliferation response is typically seen within 2 months of initiating combination therapy. The use of synthetic versus natural progestogens appears to increase this response. Several studies have shown increased breast cell proliferation in response to sequential conjugated equine estrogens-medroxyprogesterone acetate (CEE-MPA), whereas treatment with percutaneous estradiol and oral natural micronized progesterone (E2-P) is not significantly associated with this potentially hazardous side effect.
Gene expression analysis of healthy postmenopausal women in a prospective clinical study indicated that genes encoding for epithelial proliferation markers Ki-67 and progesterone receptor B mRNA are differentially expressed in women using hormone therapy with natural versus synthetic estrogens. Two 28-day cycles of daily estradiol (E2) gel 1.5 mg and oral micronized progesterone (P) 200 mg/day for the last 14 days of each cycle did not significantly increase breast epithelial proliferation (Ki-67 MIB-1 positive cells) at the cell level nor at the mRNA level (MKI-67 gene). By contrast, two 28-day cycles of daily oral conjugated equine estrogens (CEE) 0.625 mg and oral medroxyprogesterone acetate (MPA) 5 mg for the last 14 days of each cycle significantly increased proliferation at both the cell level and at the mRNA level, and significantly enhanced mammographic breast density, an important risk factor for breast cancer. In addition, CEE/MPA affected around 2,500 genes compared with just 600 affected by E2/P. These results suggest that HT with natural estrogens affects a much smaller number of genes and has less-adverse effects on the normal breast in vivo than conventional, synthetic therapy.
Preliminary results from the mammographic study showed a significant increase in mammographic density of at least one BI-RADS density class in seven of 37 patients (18.9%) using synthetic hormones (CEE/MPA group) between baseline and days 54-56. By contrast, only two of the 32 patients (6.3%) using natural hormones (E2/P group) had an increase in mammographic density of at least one density class over the same period.
We work together with patients and their health care providers to customize medications that meet each individual's specific needs.
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