Drug Administration-approved Product Research Articles

Transungual Penetration and Antifungal Activity of Prescription and Over-the-Counter Topical Antifungals: Ex Vivo Comparison.

Topical antifungals for toenail onychomycosis must penetrate the nail to deliver an inhibitory concentration of free drug to the site of infection. In two ex vivo experiments, we tested the ability of topical antifungals to inhibit growth of Trichophyton rubrum and Trichophyton mentagrophytes, the most common causative fungi in toenail onychomycosis. Seven topical antifungals were tested: three U.S. Food and Drug Administration-approved products indicated for onychomycosis (ciclopirox 8% lacquer; efinaconazole 10% solution; tavaborole 5% solution) and four over-the-counter (OTC) products for fungal infections (tolnaftate 1% and/or undecylenic acid 25% solutions). The ability to inhibit fungal growth was tested in the presence and absence of keratin. Products were applied either to human cadaverous nails or keratin-free cellulose disks prior to placement on an agar plate (radius: 85mm) seeded with a clinical isolate of T. rubrum or T. mentagrophytes. After incubation, the zone of inhibition (ZI), defined as the radius of the area of no fungal growth, was recorded. In the nail penetration assay, average ZIs for efinaconazole (T. rubrum: 82.1mm; T. mentagrophytes: 63.8mm) were significantly greater than those for tavaborole (63.5mm; 39.1mm), ciclopirox (7.4mm; 3.6mm) and all OTC products (range: 10.5-34.2mm against both species; all P < 0.001). In the cellulose disk diffusion assay, efinaconazole and tavaborole demonstrated maximal antifungal activity against both species (ZIs = 85mm); average ZIs against T. rubrum and T. mentagrophytes were smaller for ciclopirox (59.0 and 55.7mm, respectively) and OTC products (range: 31.2-57.8mm and 25.7-47.7mm, respectively). Among all antifungals tested, the ability to penetrate human toenails to inhibit growth of both T. rubrum and T. mentagrophytes was greatest for efinaconazole, followed by tavaborole. These results indicate superior transungual penetration of efinaconazole compared to the other antifungals, suggesting lower keratin binding in the nail.

Biochemical Stability and Microbial Control of Reconstituted DaxibotulinumtoxinA-lanm for Injection.

DaxibotulinumtoxinA-lanm for injection (DAXI) is a unique US Food and Drug Administration-approved product comprising daxibotulinumtoxinA and a stabilizing excipient peptide (RTP004). DAXI has a longer-labeled shelf life (72 h) following reconstitution than other botulinum toxin type A products. Here, we report the stability and microbial control of reconstituted DAXI when stored at 2 °C-8 °C over a period of 36 days (Study 1) and 7 days (Study 2) following reconstitution with unpreserved or preserved saline. The pH and biological activity of reconstituted DAXI in the 50 U/vial and 100 U/vial formats remained stable at the final assessed time point in both preserved and unpreserved saline when refrigerated (2 °C-8 °C). No changes in recoverable 150 kDa neurotoxin (measured by enzyme-linked immunosorbent assay) were observed over 6 days of refrigeration. Bacterial growth or pathogen proliferation was not observed in DAXI reconstituted in preserved or unpreserved saline in both studies.

Monoamine Oxidase Inhibitors and Clinically Relevant Drug Interactions: A Guide for Preventing Serotonin Toxicity and Hypertensive Reactions

This article describes and clarifies the two significant interactions encountered with monoamine oxidase inhibitors (MAOIs): serotonin toxicity and the tyramine pressor response. This is important because of the amount of inaccurate and misleading information (including in United States Food and Drug Administration-approved product information sheets and online resource and database systems) promulgated over the last few decades, which continues to cause confusion and undue concern. There are few if any clinically relevant CYP450 interactions with psychotropic drugs and no significant pharmacokinetic interactions. Serotonin toxicity is now well understood and only occurs in a problematic form when MAOIs are given in conjunction with serotonin reuptake inhibitors. Major prolonged elevations of blood pressure from tyramine are now less of a concern because of greatly reduced tyramine levels in foods. Therefore, MAOIs are safer and simpler to use in clinical practice than has usually been stated and should be considered earlier in the treatment algorithm for both atypical and melancholic depression. [ Psychiatr Ann . 2023;53(8):353–358.]

Food Oral Immunotherapy: A Survey Among US Practicing Allergists Conducted as a AAAAI Leadership Institute Project and Work Group Report.

Food oral immunotherapy (OIT) is an active form of treatment for food allergies. Although research in this area has been ongoing for many years, the first US Food and Drug Administration-approved product for peanut allergy treatment became available only in January 2020. Limited data exist on OIT services offered by physicians in the United States. This workgroup report was developed to evaluate OIT practices among allergists practicing in the United States. The authors developed an anonymous 15-question survey and was subsequently reviewed and approved by the American Academy of Allergy, Asthma & Immunology Practices, Diagnostics and Therapeutics Committee before distribution to the membership. The American Academy of Allergy, Asthma & Immunology electronically distributed the survey to a random sample of 780 members in November 2021. In addition to questions specific to food OIT, the survey included questions on demographics and professional characteristics of the responders. A total of 78 members completed the survey, yielding a 10% response rate. Fifty percent of responders were offering OIT in their practice. There was a significant difference in experience in OIT originating from research trials in academic versus nonacademic centers. Generally, OIT practices were similar in both settings for the number of foods offered, the performance of oral food challenges before initiating treatment, the number of new patients to whom OIT was offered to per month, and age groups OIT to whom was offered. Almost all of the reported barriers to OIT were similar between settings: staff and time limitations, concerns about safety and anaphylaxis, the need for more education on how to perform, inadequate compensation, and that it was not a significant demand from patients. Clinic space limitations were significantly different and more prominent in academic settings. Our survey revealed interesting trends in the practice of OIT across the United States, with some significant differences arising when academic and nonacademic settings were compared.

Medical Cannabis Received by Patients According to Qualifying Condition in a US State Cannabis Program: Product Choice, Dosing, and Age-Related Trends

Little is known about the distribution of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) to patients participating in state medical cannabis programs. The Minnesota cannabis program requires third-party testing of products with limited formulations of cannabis for distribution to patients. To characterize the distribution of cannabis products, their CBD/THC content, and dosing among patients with qualifying conditions. This is a retrospective analysis of ∼50% of registered users receiving medical cannabis in Minnesota (June 16, 2016, to November 15, 2019). Data included formulation, CBD/THC prescribed doses, and qualifying conditions. The primary end points were calculated using daily dose and duration of use. Comparisons were made for CBD and THC total daily dose dispensed, patient age, and approved product. Nonparametric statistical tests were used (significance was set at p < 0.05). A total of 11,520 patients were listed with 1 qualifying condition. The most common condition was intractable pain (60.0%). Median dispensation duration varied from 53 days (cancer) to 322 days (muscle spasms). Most (≥62.8%) patients across all qualifying conditions received both CBD and THC. Median THC dose was lower in older (≥65 years) compared with younger adults with intractable pain (p < 0.0001) and cancer patients (p = 0.0152), and the same pattern was found CBD dose with seizure (p = 0.0498) patients. For commercial products with Food and Drug Administration indications, the median CBD total daily dose was 86.9% lower than the recommended doses for patients with seizures (Epidiolex: Jazz Pharmaceuticals, Palo Alto CA) and median THC total daily dose was 65.3% (Syndros: Benuvia Manufacturing, Round Rock, TX) or 79.3% lower (Marinol: Banner Pharmacaps, Inc., High Point, NC) for cancer patients. A majority of patients received products containing both CBD and THC. Dosages varied by age group and were lower than recommended for conditions with Food and Drug Administration-approved products. Complex pharmacokinetics of THC and CBD, possible age-related changes in physiology, unknown efficacy, and potential for drug interactions all increase the need for monitoring of patients receiving cannabis products. (Curr Ther Res Clin Exp. 2023; 84:XXX-XXX).

Smart Bioreso rbable Polymers for Pharmaceuticals and Medical Devices

Smart bioresorbable polymers play a crucial role in pharmaceutical drug delivery and medical device applications. Among several bioresorbable polymers, poly lactic-co-glycolic acid and poly lactic acid are two common synthetic polymers used for various applications. Owing to their stimuli-sensitive behavior, they are called ‘smart polymers.’ Numerous commercial applications have demonstrated the effective use of bioresorbable polymer-based drug delivery systems for the treatment and diagnosis of several diseases and disorders. This review provides an overview of bioresorbable polymers as well as the associated commercial technologies and applications in the United States Food and Drug Administration-approved products and in drug delivery and medical devices.

Real-world evidence for U.S. Food and Drug Administration-approved oncology products, 2015 to 2020.

280 Background: Since the 21st Century Cures Act, there has been growing interest in using real-world evidence (RWE) to support regulatory filings for new drugs and indications. The goal of this study was to provide a comprehensive source of RWE use cases of U.S. Food and Drug Administration (FDA) approvals for oncology products. Methods: A systematic review of FDA new drug applications (NDAs) and biologics license applications (BLAs) from 1/2015-2/2020 for approved oncology products was performed. Data on the RWE study were extracted (data source, study design, statistical methods, results), and corresponding FDA comments were synthesized to identify patterns of the FDA’s review. Results: We identified 102 NDAs and BLAs, 8 (8%) of which included RWE, all post-Cures Act (see Table). RWE supporting avelumab, axicabtagene ciloleucel, and avapritinib were received positively and used by the FDA in their approval decision. RWE results were used to provide contextualization to the pivotal trial, rather than statistical comparison. Common data sources included Flatiron (38%) and chart reviews (38%). FDA critiques included lack of a priori study protocol, incomparability with the pivotal trial population and endpoints, and uncontrolled confounding. Conclusions: There have been few examples of RWE in oncology submissions, and most served to complement clinical trial results. To meet FDA standards, RWE studies should be clearly designed and discussed with the FDA and include robust methods to minimize bias. [Table: see text]

Physiologically Based Pharmacokinetic Model Predictions of Panobinostat (LBH589) as a Victim and Perpetrator of Drug-Drug Interactions.

Panobinostat (Farydak) is an orally active hydroxamic acid-derived histone deacetylase inhibitor used for the treatment of relapsed or refractory multiple myeloma. Based on recombinant cytochrome P450 (P450) kinetic analyses in vitro, panobinostat oxidative metabolism in human liver microsomes was mediated primarily by CYP3A4 with lower contributions by CYP2D6 and CYP2C19. Panobinostat was also an in vitro reversible and time-dependent inhibitor of CYP3A4/5 and a reversible inhibitor of CYP2D6 and CYP2C19. Based on a previous clinical drug-drug interaction study with ketoconazole (KTZ), the contribution of CYP3A4 in vivo was estimated to be ∼40%. Using clinical pharmacokinetic (PK) data from several trials, including the KTZ drug-drug interaction (DDI) study, a physiologically based pharmacokinetic (PBPK) model was built to predict panobinostat PK after single and multiple doses (within 2-fold of observed values for most trials) and the clinical DDI with KTZ (predicted and observed area under the curve ratios of 1.8). The model was then applied to predict the drug interaction with the strong CYP3A4 inducer rifampin (RIF) and the sensitive CYP3A4 substrate midazolam (MDZ) in lieu of clinical trials. Panobinostat exposure was predicted to decrease in the presence of RIF (65%) and inconsequentially increase MDZ exposure (4%). Additionally, PBPK modeling was used to examine the effects of stomach pH on the absorption of panobinostat in humans and determined that absorption of panobinostat is not expected to be affected by increases in stomach pH. The results from these studies were incorporated into the Food and Drug Administration-approved product label, providing guidance for panobinostat dosing recommendations when it is combined with other drugs.

A Medical Mystery: Unexplained Renal Failure in Burn Patients.

The objective of this study was to review the investigation that uncovered the medical mystery of burn patients developing unexpected renal failure. The authors examined published and unpublished manuscripts and case reports, as well as conducted personal interviews with primary sources. In the late 1970s, emergence of resistant bacterial strains to the topical antimicrobial silver sulfadiazine occurred at the University of Virginia Medical Center. In the search for an alternative topical antimicrobial with known coverage of Pseudomonas aeruginosa, Furacin Soluble Dressing was substituted. However, Furacin Soluble Dressing produced an unexpected toxicity syndrome of hyperosmolality, metabolic gap acidosis, hypercalcemia, and ultimately renal failure. In a search for an antimicrobial with an improved spectrum against Pseudomonas, a Federal Drug Administration-approved product was used to treat large surface area burns. An unexpected toxicity syndrome developed which was traced to the polyethylene glycol base of Furacin Soluble Dressing. This substance was absorbed through the burn wounds, metabolized, and resulted in a toxicity syndrome leading to renal failure. The burn community should be cautious when using products that may be approved as nontoxic for small surface area application, as they may have unexpected medical side effects when used with large surface area burns.

Evaluation of XSTAT® and QuickClot® Combat Gauze® in a Swine Model of Lethal Junctional Hemorrhage in Coagulopathic Swine.

Hemorrhage is associated with most potentially survivable deaths on the battlefield. Effective and field-tested products are lacking to treat junctional and noncompressible injuries. XSTAT® is a newly developed, U.S. Food and Drug Administration-approved product designed to treat junctional hemorrhage. The Committee on Tactical Combat Casualty Care has recently approved the product for use as part of its treatment guidelines, but data are lacking to assess its efficacy in different wounding patterns and physiologic states. Dilutional coagulopathy was induced in 19 large (70-90kg), healthy, male swine by replacing 60% of each animal's estimated blood volume with room temperature Hextend ®. After dissection, isolation, and lidocaine incubation, uncontrolled hemorrhage was initiated by transection of both axillary artery and vein. Free bleeding was allowed to proceed for 30 seconds until intervention with either XSTAT or QuickClot® Combat Gauze® (CG) followed by standard backing. Primary outcomes were survival, hemostasis, and blood loss. XSTAT-treated animals achieved hemostasis in less time and remained hemostatic longer than those treated with CG. Less blood was lost during the first 10 minutes after injury in the XSTAT group than the CG group. However, no differences in survival were observed between XSTAT-treated and CG-treated groups. All animals died before the end of the observation period except one in the XSTAT-treated group. XSTAT performed better than CG in this model of junctional hemorrhage in coagulopathic animals. Continued testing and evaluation of XSTAT should be performed to optimize application and determine appropriate indications for use.

Drug interactions involving antiepileptic drugs: Assessment of the consistency among three drug compendia and FDA-approved labels

Interactions of antiepileptic drugs (AEDs) with other substances may lead to adverse effects and treatment failure. To avoid such interactions, clinicians often rely on drug interaction compendia. Our objective was to compare the concordance for twenty-two AEDs among three drug interaction compendia (Micromedex, Lexi-Interact, and Clinical Pharmacology) and the US Food and Drug Administration-approved product labels. For each AED, the overall concordance among data sources regarding existence of interactions and their classification was poor, with less than twenty percent of interactions listed in all four sources. Concordance among the three drug compendia decreased with the fraction of the drug excreted unchanged and was greater for established inducers of hepatic drug-metabolizing enzymes than for the drugs that are not inducers (R-square=0.83, P<0.01). For interactions classified as contraindications, major, and severe, concordance among the four data sources was, in most cases, less than 30%. Prescribers should be aware of the differences between drug interaction sources of information for both older AEDs and newer AEDs, in particular for those AEDs which are not involved in hepatic enzyme-mediated interactions.

Women's Perspectives on Female-Initiated Barrier Methods for the Prevention of HIV in the Context of Methamphetamine Use and Partner Violence

BackgroundFemale-initiated barrier methods for the prevention of HIV may be an effective alternative for drug-using women who are unable to negotiate safe sex, often as a result of physical and/or sexual partner violence. MethodsUtilizing a SAVA (substance abuse, violence, and AIDS) syndemic framework, we qualitatively examined perspectives on female condoms and vaginal microbicides among 18 women with histories of methamphetamine abuse and partner violence in San Diego, California. FindingsMost women were not interested in female condoms owing to perceived discomfort, difficulty of insertion, time-intensive effort, and unappealing appearance. Alternatively, most women viewed vaginal microbicides as a useful method. Positive aspects included convenience, ability to disguise as a lubricant, and a sense of control and empowerment. Concerns included possible side effects, timing of application, and unfavorable characteristics of the gel. Acceptability of female-initiated barrier methods was context dependent (i.e., partner type, level of drug use and violence that characterized the sexual relationship). ConclusionsFindings indicate that efforts are needed to address barriers identified for vaginal microbicides to increase its uptake in future HIV prevention trials and marketing of future Food and Drug Administration-approved products. Strategies should address gender-based inequalities (e.g., partner violence) experienced by drug-using women and promote female empowerment. Education on female-initiated barrier methods is also needed for women who use drugs, as well as health care providers and other professionals providing sexual health care and contraception to women with histories of drug use and partner violence.

Cross‐linked gelatin microspheres with continuously tunable degradation profiles for renal tissue regeneration

Collagen and gelatin-based biomaterials are widely used in tissue engineering applications. Various methods have been reported for the cross-linking of these macromolecules for the purpose of delaying their biodegradation to prolong their in vivo residence (in tissue engineering applications) or tailoring their drug releasing capacity (when used as drug carriers). In this study, a carbodiimide-based cross-linking method, also used in the production of United States Food and Drug Administration-approved products, was employed to obtain differentially cross-linked gelatin beads. The colorimetric determination of the in vitro enzymatic susceptibility of the beads indicated that the resistance to degradation linearly correlated with the concentration of carbodiimide used for the cross-linking reaction. This result was also confirmed in vivo by the histological evaluation of the residence time of orthotopically injected cell-seeded beads. These data would indicate that the production of gelatin-based microbeads with tunable degradation profiles might be applicable toward the development of products that catalyze regeneration of kidney and other solid organs.

Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma

Current therapy for glioblastoma multiforme is insufficient, with nearly universal recurrence. Available drug therapies are unsuccessful because they fail to penetrate through the region of the brain containing tumor cells and they fail to kill the cells most responsible for tumor development and therapy resistance, brain cancer stem cells (BCSCs). To address these challenges, we combined two major advances in technology: (i) brain-penetrating polymeric nanoparticles that can be loaded with drugs and are optimized for intracranial convection-enhanced delivery and (ii) repurposed compounds, previously used in Food and Drug Administration-approved products, which were identified through library screening to target BCSCs. Using fluorescence imaging and positron emission tomography, we demonstrate that brain-penetrating nanoparticles can be delivered to large intracranial volumes in both rats and pigs. We identified several agents (from Food and Drug Administration-approved products) that potently inhibit proliferation and self-renewal of BCSCs. When loaded into brain-penetrating nanoparticles and administered by convection-enhanced delivery, one of these agents, dithiazanine iodide, significantly increased survival in rats bearing BCSC-derived xenografts. This unique approach to controlled delivery in the brain should have a significant impact on treatment of glioblastoma multiforme and suggests previously undescribed routes for drug and gene delivery to treat other diseases of the central nervous system.

Unjustified Increase in Cost of Care Resulting From U.S. Food and Drug Administration Approval of Makena (17α-Hydroxyprogesterone Caproate)

U.S. Food and Drug Administration (FDA) approval of 17α-hydroxyprogesterone caproate for the indication of decreasing the risk of preterm delivery in those high-risk patients who previously had spontaneous preterm birth has come at considerable cost to the health care system. Weekly injections provided by compounding pharmacies starting at 16-20 weeks of gestation and continuing until 36 weeks currently cost the health care system $200 to $300 per pregnancy. This cost is significantly less than the costs associated with delivering and caring for preterm children. Makena, by KV Pharmaceutical, the same 17α-hydroxyprogesterone caproate product, is priced at $1,500 per injection, or a projected cost of $30,000 per pregnancy. With approximately 132,000 pregnancies being eligible for treatment annually, this increase in cost of 75-150 times what previously had been paid far exceeds the benefits derived from the FDA-approved Makena when compared with previously available compounded versions of 17α-hydroxyprogesterone caproate. This increased health care cost is not justified at this time. The price barrier to access imposed by KV Pharmaceutical actually could result in an increase in preterm deliveries over current rates. Actions are needed by the FDA, national societies, and the manufacturer to ensure that all high-risk patients continue to get the needed therapy to reduce the number of preterm births.

Evaluation of Contraindicated Drug-Drug Interaction Alerts in a Hospital Setting

Risks associated with contraindicated drug-drug interaction alerts (CDDIAs) should always outweigh benefits. Misclassified CDDIAs should be eliminated. To review CDDIAs and determine if they are contraindicated according to Food and Drug Administration-approved product labeling and if there are circumstances in which contraindicated interactions are acceptable. A cross-sectional observational and quality improvement study was conducted over two 1-year periods. The 20 most common CDDIAs from May 2007 to May 2008 and all CDDIAs from April 2008 to April 2009 were collected at a large teaching hospital. Horizon Meds Manager used First DataBank as the knowledge base for decision support. Interactions were deemed truly contraindicated if listed in the contraindications section of the labeling of at least one of the interacting drugs. Alerts were grouped by drug and pharmacologic class to evaluate the evidence supporting the relevance of these interactions. An expert panel determined when an alert was misclassified. A medical advisory committee determined whether a contraindicated drug-drug combination was acceptable. Twelve (60%) of the most common 20 contraindicated interaction pairs from 2007 to 2008 were inappropriately classified. Half of the alerts were not truly contraindicated. The 8 truly contraindicated drug-drug pairs were ketorolac and other nonsteroidal antiinflammatory drugs or oral solid potassium products and anticholinergics. Half of these interactions were subsequently deemed acceptable under specific circumstances. Similar results were found in the second year, with only 55.1% of all CDDIAs being truly contraindicated despite eliminating some of the alerts that were misclassified in the first year. Nearly three fourths of legitimate CDDIAs were deemed acceptable under specific circumstances. Most contraindicated drug-drug interaction alerts from a commercial knowledge base were inappropriately categorized and could be downgraded. Some contraindicated drug combinations are permissible under specific circumstances. Alerts suggesting that certain drugs should never be used together, but their use together is sometimes acceptable, contribute to alert fatigue.

Successful Experience Utilizing Dexrazoxane Treatment for an Anthracycline Extravasation

To describe a successful case of dexrazoxane treatment after an extravasation of doxorubicin and share a creative solution for formulary cost management. A 42-year-old female diagnosed with breast cancer was receiving doxorubicin as adjuvant treatment. The patient recently underwent a right mastectomy for a 3-centimeter grade 3 invasive ductal carcinoma. Three of 20 lymph nodes were positive, and the patient was stage 2B at presentation, with an estrogen receptor/progesterone receptor-positive and HER-2/neu-negative tumor. At an outside hospital, the patient was receiving doxorubicin through an infusion port when extravasation was noted after approximately 15 mL had been infused. She was transferred to Riverside Methodist Hospital and dexrazoxane treatment was initiated within 6 hours after extravasation. She received a full 3-day course of dexrazoxane treatment without complication and was discharged home. Significant delays in chemotherapy administration were avoided, and the patient successfully completed her planned chemotherapy course. Dexrazoxane has the potential to minimize tissue damage and treatment delays after an anthracycline extravasation. Although dexrazoxane is commercially marketed for 2 separate treatment indications, Totect is the Food and Drug Administration-approved product for anthracycline extravasations. Facilities administering anthracyclines should proactively resolve how to obtain, process, prepare, and administer this antidote to a patient within 6 hours of an extravasation event. Developing a preprinted chemotherapy extravasation order may facilitate the incorporation of the most recent Oncology Nursing Society guidelines to utilize dexrazoxane for an anthracycline extravasation. Cost sharing with other institutions may offer a creative solution to lessen the financial impact of stocking dexrazoxane therapy. Ensuring expedient treatment and accessibility to dexrazoxane therapy after an anthracycline extravasation is critical to the success of the treatment. All facilities utilizing anthracycline chemotherapy should purchase dexrazoxane or secure agreements with other facilities to guarantee the administration of this medication should extravasation occur.

Identification and treatment of acute repetitive seizures in children and adults

Acute repetitive seizures are a predictable component of a patient's seizure disorder, historically distinct from the patient's other epileptic seizures in type, frequency, severity, or duration, and with an onset easily recognized by caregiver and physician. Onset has a consistent predictable component (such as aura or prodrome, which may be a convulsive or nonconvulsive symptom, or characteristic single or multiple seizures) that is predictably and temporally linked to subsequent seizures. Typically there is recovery between seizures. Episodes may or may not progress to a prolonged seizure or to status epilepticus but may be predictable for each patient based on history. Acute repetitive seizures may include any type of epileptic seizure and may occur at any age. Other terms for acute repetitive seizures include cluster, serial, recurrent, or crescendo seizures. Treatment should only be administered by caregivers who in the opinion of the prescriber are capable of monitoring the clinical response and recognize when the response is such that immediate professional evaluation or care is necessary. Caregivers must be comfortable so that they feel capable of recognizing when and how to treat. The prescriber and caregiver should have a written plan on when to treat and what to observe and do after treatment. The most immediate treatment for out of hospital care and the only US Food and Drug Administration-approved product for acute repetitive seizures is rectal diazepam gel administered at a dose of 0.2 to 0.5 mg/kg, depending on age and weight (Class I evidence). Treatment may produce central nervous system depression. Oral, buccal, and sublingual benzodiazepines (lorazepam, diazepam) are also used for treatment but only if the risk of aspiration is not a concern and recognizing that absorption time will be increased (Class III evidence). Nasal benzodiazepine products, available in some countries, are not yet available in the United States.

REVIVING AN OLD DRUG

IT S NOT OFTEN THAT SOMEONE CAN further a company's ambitions while advancing a more personal project at the same time. But if Paul Rubin is successful in commercializing the asthma drug zileuton, he will have managed to accomplish both of these goals. Rubin is president and chief executive officer of Critical Therapeutics Inc.(CTI), a small biopharmaceutical company in Lexington, Mass. And in his dual quest, he is leveraging two strengths from his past: an intimate knowledge of zileuton and a good working experience with the pharmaceutical services firm Rhodia Pharma Solutions. From 1987 until 1993, Rubin, a medical doctor, was in charge of a group at Abbott Laboratories responsible for the development of zileuton. When the drug was approved in 1996 as Zyflo, it became the only Food & Drug Administration-approved product that works by blocking the activity of 5-lipoxygenase, the main enzyme responsible for the formation of a family ...

Growth factor therapy to improve soft tissue healing.

The advent of new U.S. Food and Drug Administration-approved products containing growth factors to improve soft tissue healing signifies a new era for wound healing. Over the last decade, some clinical growth factor studies have been promising, whereas others have not shown any positive effect. What many of these studies have shown is that the state of a healing wound is not only dependent on its growth factor milieu but also on other variables (wound care, tissue oxygen state, bacteria count, and nutritional status of the patient). This article describes recent progress with growth factors on soft tissue structures (skin, mucosa, and nerve) relevant to the facial plastic and reconstructive surgeon.