Generic Patches Research Articles

(017) Systemic Estradiol Menopause Management: Return to the Old-Fashioned Way

Abstract Introduction The mean systemic estradiol value in menopausal women is < 10 pg/ml, consistent with ovarian failure. Such low values are associated with multiple symptoms including hot flashes, night sweats, insomnia, mood changes and irritability, cognitive changes, weight gain and slowed metabolism. Contemporary management with systemic estradiol, maximizing safety and efficacy, emphasizes non-oral, non-injection estradiol replacement therapies including systemic daily gels, twice weekly or weekly patches or three-month vaginal rings. Most women (>60%) who try these systemic therapies in our sexual medicine clinic have been successful at reducing bothersome symptoms. We have identified a subset of women who cannot achieve sufficient symptom relief despite using contemporary estradiol strategies due to lack of efficacy, negative side effects, (rings cannot stay in the vagina or values are too high initially and then too low, patches cause rashes or fall off, gels are too messy) or financial concerns. For these patients, we have advised a return to the “old-fashioned way” using weekly intramuscular (IM) injection of either estradiol valerate or cypionate. Estradiol cypionate was first described as well as introduced for medical use in 1952. Objectives This study examines the experiences of this subset of women in one practice using weekly injections of estradiol valerate or cypionate for either efficacy or financial reasons. Methods This chart review identified a subset of 16 patients (mean age 59 +/− 8 years) at a single site who had been prescribed estradiol valerate or cypionate when symptoms of genitourinary syndrome of menopause (GSM) persisted despite use of estradiol replacement gels, patches or rings, or cost was prohibitive. We have advised weekly IM injection of either estradiol valerate (20 mg/ml; starting dose 0.05 ml or 1 mg) or estradiol cypionate (5 mg/ml; starting dose 0.2 ml or 1 mg). We compared relief of bothersome symptoms from earlier estradiol treatments to current IM injection and compared monthly costs of each treatment based on GoodRx prices, assuming medications were not covered by insurance. Results All patients using weekly injections of estradiol valerate or cypionate had their estradiol-based GSM symptoms ameliorated without complaint of inconvenience or discomfort using injections. The risks of IM injections of estradiol are similar to those of topical administration, requiring concomitant progesterone use in women with a uterus. Concerning finances, using a GoodRx coupon, a 5 ml bottle of estradiol valerate costs approximately $50 and should last at least one year, reducing monthly cost to approximately $5/month. A 5 ml bottle of estradiol cypionate costs approximately $150 and should last at least 6 months, thus about $25/month. In contrast, generic patches are approximately $40/month, gels $150/month and the ring $170/month. While there remains an abhorrence for injections, the motivation for systemic estradiol replacement superseded any inconvenience of using an injectable medication and the 27-gauge ½ inch needle is associated with minimal pain. No significant side effects were noted with IM injection. Conclusions For certain individuals, sometimes the “old-fashioned way” works better both in terms of efficacy and cost, providing relief of bothersome menopausal symptoms. Disclosure No.

Systemic Estradiol Menopause Management: Return to the Old-Fashioned Way

ABSTRACT Introduction Low systemic estradiol values (<10 pg/ml) experienced by menopausal women are associated with multiple symptoms including hot flashes, night sweats, insomnia, mood changes/irritability, vaginal dryness, dyspareunia, dysuria, low libido, reduced arousal/orgasm, cognitive changes, weight gain and slowed metabolism. Intramuscular estradiol cypionate was first described for medical use in 1952 to treat symptoms of menopausal ovarian failure. Systemic management has evolved, including daily gels, weekly/twice weekly patches and three-month vaginal rings. These therapies have successfully reduced bothersome symptoms in >60% women presenting to our clinic. A subset of women cannot achieve sufficient symptom relief using these strategies due to lack of efficacy, negative side effects, (rings cannot stay in the vagina; values are too high initially and then too low; patches cause rashes or fall off; gels are too messy) or financial concerns. For these patients, we have advised returning to the “old-fashioned way” using weekly or twice weekly intramuscular (IM) injection of either estradiol valerate or cypionate. Objective This study examines experiences of this subset of women in our practice using injections of estradiol valerate or cypionate for either enhancing efficacy or financial reasons. Methods This chart review identified 22 patients (mean age 61 +/- 8 years) who had been prescribed estradiol valerate or cypionate when symptoms of genitourinary syndrome of menopause (GSM) persisted despite use of estradiol replacement gels/patches/rings, or cost was prohibitive. We have advised weekly/twice weekly IM injection of either estradiol valerate (20 mg/ml; starting dose 0.05 ml (1 mg) weekly or 0.025 ml (0.5 mg) twice weekly) or estradiol cypionate (5 mg/ml; starting dose 0.2 ml weekly (1 mg) or 0.1 ml (0.5 mg twice weekly), utlizing 1 ml syringes with 27-gauge ½ inch needle. Injections were administered into the vastus lateralis on the antero-lateral surface at mid-thigh. Alcohol was used to prepare the skin, and compression was applied for 2 minutes after the injection. We compared relief of bothersome symptoms from earlier estradiol treatments to current IM injection and monthly costs of each treatment based on GoodRx prices, assuming medications were not covered by insurance. Results All patients using injections of estradiol valerate or cypionate had their estradiol-based GSM symptoms ameliorated without complaint of inconvenience or discomfort using injections. All described injection pain as minimal. No significant side effects were noted with IM injection. The risks of IM injections of estradiol are similar to those of topical administration, requiring concomitant progesterone use in women with a uterus. Concerning finances, using a GoodRx coupon, a 5 ml bottle of estradiol valerate lasting at least a year costs approximately $50, reducing monthly cost to approximately $5/month. A 5 ml bottle of estradiol cypionate lasting at least 6 months costs approximately $150, thus about $25/month. In contrast, generic patches can cost approximately $40/month, gels $150/month and the ring $170/month. Conclusions While there remains an aversion to injections in some patients, the motivation for IM systemic estradiol replacement superseded any inconvenience. For certain individuals, the “old-fashioned way” works better both in terms of efficacy and cost, providing relief of bothersome GSM symptoms. Disclosure No

A New Integrated Approach Based on the Iterative Super-Resolution Algorithm and Expectation Maximization for Face Hallucination

This paper proposed and verified a new integrated approach based on the iterative super-resolution algorithm and expectation-maximization for face hallucination, which is a process of converting a low-resolution face image to a high-resolution image. The current sparse representation for super resolving generic image patches is not suitable for global face images due to its lower accuracy and time-consumption. To solve this, in the new method, training global face sparse representation was used to reconstruct images with misalignment variations after the local geometric co-occurrence matrix. In the testing phase, we proposed a hybrid method, which is a combination of the sparse global representation and the local linear regression using the Expectation Maximization (EM) algorithm. Therefore, this work recovered the high-resolution image of a corresponding low-resolution image. Experimental validation suggested improvement of the overall accuracy of the proposed method with fast identification of high-resolution face images without misalignment.

Delayed market entry for generic buprenorphine patches could have cost NHS £500,000, study concludes

Delayed market entry for generic buprenorphine patches could have cost NHS £500,000, study concludes

Molecular State of Active Pharmaceutical Ingredients in Ketoprofen Dermal Patches Characterized by Pharmaceutical Evaluation.

The molecular states of ketoprofen and the interaction between ketoprofen and other pharmaceutical excipients in the matrix layer were examined to determine their effect on the pharmaceutical properties of original and generic ketoprofen dermal patches (generic patches A and B). Molecular states of ketoprofen were evaluated using polarized light microscopy, Raman spectroscopy and powder X-ray diffraction. For the original ketoprofen patch, crystalline components were not observed in the matrix layer. However, crystalline ketoprofen was observed in the two generic ketoprofen patches. Moreover, the ketoprofen exhibited hydrogen bonding with the pharmaceutical excipients or patch materials in the generic products. Skin permeation of ketoprofen from the patches was evaluated using hairless mouse skin. Twelve hours after application, the original patch demonstrated the highest level of cumulative skin permeation of ketoprofen. This was followed by generic patch B while generic patch A showed the lowest level of permeation. Fluxes were calculated from the skin permeation profiles. The original patch was approx. 2.4-times faster compared with generic patch A and approximately 1.9-times faster compared with generic patch B. This investigation suggested that pharmaceutical properties such as skin permeability for these types of products are affected by the precipitation of crystalline ketoprofen in the matrix layer and the interaction of ketoprofen with the pharmaceutical excipients or patch materials.

Generic patches containing fentanyl: In vitro equivalence and abuse deterrent evaluation according to EMA and FDA guidelines

The aim of this work was to characterize in vitro and ex vivo the performances of Durogesic and of two bioequivalent generic products, by evaluating: (a) fentanyl release; (b) fentanyl permeation across porcine skin and (c) fentanyl ease of extraction. Additional characteristics studied are the effect of temperature and skin integrity, applied individually or combined, to check a possible synergism. The two generic patches resulted equivalent to the originator according to the new Guideline. Nevertheless, the same data reported in a different way, i.e. considering the total amount of drug permeated from the whole patch over the application time, highlight differences among the patches. The additional tests performed showed that skin integrity does not represent a barrier for fentanyl permeation across the skin, regardless of the type and complexity of the patch. The effect of temperature resulted critical for two out of three patches, probably due to the different composition and to the different structure. The combination of skin damage and elevated temperature did not produce a synergistic effect. Fentanyl extraction was different for the different products and variable according to the conditions used.The results reported in the present work underline the influence of patch composition and complexity on fentanyl extraction, release and skin permeation, in particular in conditions that can be critical, such as elevated temperature. In particular, the effect of critical variables, such as skin integrity and temperature, should be addressed to in the development of a new or new generic patch and new discriminant tests should be developed.

Current Landscape and Trends in Transdermal Drug Delivery Systems

"Generic pharmaceutical marketers are increasingly keen to have a presence in generic patches as they represent high-margin, high entry-barrier opportunities with a smaller field of competition".

Comparative Study of Skin Permeation Profiles between Brand and Generic Tulobuterol Patches

Tulobuterol patches are long-acting bronchodilators for percutaneous absorption including the β(2)-adrenoreceptor agonist tulobuterol, as a main ingredient, used for long-term management of pediatric asthma. Since patients who have pediatric asthma often also have atopic dermatitis in which the skin barrier is impaired, we compared the skin penetration profiles of the brand and generic patches using a skin barrier-impaired rat model. Skin penetration was significantly (p<0.001) higher in the generic patches compared with the brand patch, suggesting that it is important to understand the pharmaceutical properties of available products by giving careful consideration not only to the patient's asthma control but also to their skin condition before using tulobuterol patches.

Medikolegale Aspekte bei der Anwendung von Fentanyl-Pflastern

The use of fentanyl patches has become accepted as standard in Germany for the treatment of chronic and cancer pain. Recently generic fentanyl patches were launched but in contrast to the original patches the new patches are without labels concerning the concentration. There is not only a difference of ca 30% in the fentanyl concentration among the different generic patches, there is also a variation in the size. Especially in hospitals, nursing homes or in emergency cases the dose of the patches cannot be distinguished by doctors, nurses or other healthcare providers which can lead to overdoses or to withdrawal reactions with one of the strongest opioids available. In cases where problems occur the prescribing doctor will be held responsible.

Generic Transdermal Patches for Chronic Pain

Generic Transdermal Patches for Chronic Pain

Adaptive generation of surfaces in volume data

The generation of polygonal approximations of iso-surfaces or separating surfaces in volume data is a major method in scientific visualization. A widespread approach for this task is the so-called marching cubes algorithm. The marching cubes algorithm, however, has the disadvantage that the number of polygonal chains generated is considerable. The splitting box algorithm presented in this paper reduces the number of polygonal chains by adapting their size to the shape of the surface. The resulting polygonal chains offer a wide spectrum for representing the separating surface. The exact representation is achieved by a new type of generic patches calculated from the polygonal chains. Approximations of different quality may be obtained by combining the algorithm generating the patches with simple triangulations.