pulmicort and Candidiasis--Oral

Topically active inhaled corticosteroid (IC) drugs are highly effective for chronic asthma. Formalized conceptions of "high, low or safe" dosages of these drugs may be less appropriate than one of "optimal dosage". It seems reasonable to formulate a specific goal of treatment, and then fit dosage to the individual needs and tolerances of the patient rather than to a conventionalized "safe" limit, based on averaged data from different and perhaps quite dissimilar subjects. The studies reviewed here illustrate some principles applicable to the effective use of IC drugs.

Topics: Aerosols; Asthma; Beclomethasone; Budesonide; Candidiasis, Oral; Dose-Response Relationship, Drug; Drug Administration Schedule; Glossitis; Glucocorticoids; Humans; Hypothalamo-Hypophyseal System; Pituitary-Adrenal System; Prednisone; Pregnenediones; Respiratory Therapy; Risk; Time Factors; Voice Disorders

Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE.. We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily).. At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P < .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent.. In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029.

Topics: Administration, Oral; Adult; Antifungal Agents; Budesonide; Candidiasis, Oral; Double-Blind Method; Eosinophilic Esophagitis; Esophagoscopy; Female; Glucocorticoids; Humans; Male; Middle Aged; Tablets; Treatment Outcome

To review the worldwide safety data for budesonide inhalation suspension (Pulmicort Respules) to provide a budesonide inhalation suspension pediatric tolerability profile.. Clinical study data were obtained from AstraZeneca safety databases used by the US Food and Drug Administration to support the approval of budesonide inhalation suspension and from postmarketing surveillance reports (January 1, 1990, through June 30, 2002).. Completed parallel-group studies of patients with asthma 18 years and younger.. Safety data for budesonide inhalation suspension were pooled from 3 US, 12-week, randomized, double-blind, placebo-controlled studies (n = 1,018); data from their open-label extensions (n = 670) were pooled with data from a fourth US open-label study (n = 335). Data for 333 patients 18 years and younger enrolled in 5 non-US studies also were analyzed. No posterior subcapsular cataracts were reported in any study, and the frequencies of oropharyngeal events and infection with budesonide inhalation suspension were comparable with those of reference treatments. No increased risk of varicella or upper respiratory tract infection was apparent, and budesonide inhalation suspension did not cause significant adrenal suppression in studies assessing this variable. There were small differences in short-term growth velocity between children who received budesonide inhalation suspension and those who received reference treatment in 2 of 5 trials that evaluated this variable. No increased risk of adverse events was apparent from postmarketing reports.. Short- and long-term treatment with budesonide inhalation suspension, using a wide range of doses, is safe and well tolerated in children with asthma.

Topics: Administration, Inhalation; Adolescent; Asthma; Bone and Bones; Budesonide; Candidiasis, Oral; Child; Child, Preschool; Double-Blind Method; Growth; Humans; Hypothalamo-Hypophyseal System; Infant; Pituitary-Adrenal System; Respiratory Tract Infections; Suspensions

To determine therapeutically and systemically equivalent dosages of budesonide inhaled through the Turbuhaler dry powder inhalation device (Astra Pharma Production AB, Södertälje, Sweden) or pressurized metered-dose inhaler (pMDI) plus Nebuhaler spacer (Astra Pharma Production AB), we compared these devices in a randomized, open, parallel-group trial. Adults with moderate to severe asthma inhaled budesonide (0.4, 0.8, 1.6, and 2.4 mg/day), for 2 weeks at each dose level, through the Turbuhaler (n = 30) or pMDI + Nebuhaler (n = 28). Dose-dependent effects were demonstrated on asthma symptoms (p = 0.0001), daily peak expiratory flow (p = 0.02), blood eosinophils (p = 0.0001), urinary cortisol output per day (p = 0.0001), serum cortisol (p = 0.006), serum osteocalcin (p = 0.0001), and the oropharyngeal Candida colony count (p = 0.0007. analysis of covariance). The ratio of the responses to the two inhalation devices approximated 1.0 for each index measured; that is, no significant between-device difference was found (p > or = 0.29). However, the 95% confidence limits for the ratio of their respective systemic effects on osteocalcin production were 0.83 to 1.48. Thus in adults who use inhalation devices efficiently and have optimally controlled asthma, conversions from the pMDI + Nebuhaler to the Turbuhaler may reasonably be made at milligram equivalent doses of budesonide, then down-titrated to minimize possible systemic effects. Because earlier studies have shown that the Turbuhaler can double intrapulmonary drug delivery in comparison with a pMDI without a spacer, a 50% dose reduction may be indicated when converting from a pMDI to the Turbuhaler.

Topics: Administration, Inhalation; Adult; Aerosols; Aged; Anti-Inflammatory Agents; Asthma; Budesonide; Candidiasis, Oral; Colony Count, Microbial; Dose-Response Relationship, Drug; Drug Delivery Systems; Eosinophils; Female; Humans; Hydrocortisone; Lung; Male; Middle Aged; Nebulizers and Vaporizers; Osteocalcin; Pregnenediones; Respiratory Function Tests

Concomitant allergic reactions to multiple drugs are uncommon. We report the case of a 66-year-old woman who presented with concomitant sensitization to inhaled budesonide and oral nystatin presenting as allergic contact stomatitis and systemic allergic contact dermatitis. It is notable that one of the reactions was caused by oral nystatin, which generally is not considered to be allergenic due to its poor intestinal absorption. Diagnoses were confirmed on patch testing with histologic examination along with oral challenge testing. We also used challenge testing to rule out cross-reactivity among nystatin and other macrolide drugs, both antifungals and antibiotics.

Topics: Administration, Inhalation; Aged; Antifungal Agents; Budesonide; Candidiasis, Oral; Cough; Dermatitis, Allergic Contact; Female; Glucocorticoids; Humans; Nystatin; Stomatitis

Oral chronic graft versus host disease (cGVHD) is common and a major cause of morbidity and loss of quality of life in long term survivors. Cyclosporine with prednisone remains the first line therapy for oral manifestations of cGVHD. However, even with routine administration of systemic agents, many patients with oral manifestations of cGVHD do not have resolution of their disease and may benefit from incorporation of local therapy. Budesonide is a highly potent steroid which has minimal systemic side effects and being used for oral cGVHD. We designed a retrospective study to compare treatment results of patients with oral cGVHD who received topical budesonide in addition to systemic therapy that consists of combined prednisone and cyclosporine (Group A, n = 12), with the treatment results of patients who were administered the same systemic therapy alone (Group B, n = 11) to determine whether budesonide mouthwash had any advantage on response rates. Three mg topical budesonide/10 ml saline was used 3-4 times a day for up to 6 months in group A. Diagnosis, clinical staging, and treatment response scoring for cGVHD were performed according to National Institutes of Health (NIH) consensus criteria. At the baseline examination, there were no statistically significant differences in terms of median oral cGVHD examination scores between two groups. After treatment, there was statistically significant decrease in median oral cGVHD examination scores compared to baseline (P < 0.001 and 0.021), and significant differences were found between two groups (P < 0.032). Overall response rate was 83% and 36% for group A and B, respectively (P = 0.036). However, no statistically significant differences were found between median pain scores of two groups before and after treatment (P = 0.740 and P = 0.091). No major systemic side effects and oral candidiasis were observed in two groups of patients. We concluded that topical budesonide might be added to systemic therapy to obtain better response rates in patients with oral cGHVD.

Topics: Adult; Budesonide; Candidiasis, Oral; Chronic Disease; Cohort Studies; Cyclosporine; Drug Evaluation; Drug Therapy, Combination; Female; Graft vs Host Disease; Hematologic Neoplasms; Humans; Immunosuppressive Agents; Male; Middle Aged; Mouthwashes; Pain Measurement; Peripheral Blood Stem Cell Transplantation; Prednisone; Retrospective Studies; Sodium Chloride; Stomatitis; Transplantation Conditioning; Treatment Outcome

Mouth washing after inhalation of corticosteroids is effective for prevention of local adverse effects. We determined the amounts of drug residues remaining on the oropharyngeal mucosa following inhalation of budesonide (BUD) via a Turbuhaler (BUD-TH) (100 microg). Further, we studied the effects of mouth washing on the removal of drug residues by quantification of BUD in expectorated wash solution using an HPLC method. The amount of BUD recovered after gargling and rinsing for 5 s each was 19.4+/-9.4 microg, as compared to 23.8+/-13.6 microg after rinsing alone for 10 s and 18.3+/-8.9 microg after gargling alone for 10 s, though the differences were not significant. Our results indicated that about 20% of the dose was remaining on the oropharyngeal mucosa after inhalation. In a comparison of washing times, the amounts of BUD recovered were 26.3+/-3.2 microg after gargling and rinsing for 3 s each, and 19.4+/-9.3 microg after those for 5 s each. As for the effect of lag time before beginning mouth washing, the ratio of BUD recovered following mouth washing with a lag time of 1 min was 73.2%, while it was reduced to 27.8% after 10 min, as compared to immediate mouth washing following administration. Our results suggest that the amount of BUD removed by mouth washing is associated with the lag time between inhalation and mouth washing, however, not with the duration of mouth washing. We concluded that immediate mouth washing after inhalation is most useful for the removal of drugs following BUD-TH administration.

Topics: Adult; Anti-Inflammatory Agents; Budesonide; Candidiasis, Oral; Female; Glucocorticoids; Hoarseness; Humans; Male; Metered Dose Inhalers; Middle Aged; Mouthwashes; Time Factors

The influence of the dosing regimen on the occurrence of oropharyngeal complications during a trial of the anti-asthmatic aerosol steroid budesonide was assessed by systematically varying the daily dose (400, 800, 1,600 micrograms), dose frequency (b.i.d. vs. q.i.d.), and dosing schedule (AM vs. AM/PM). Dysphonia was infrequent and was not affected by any features of the treatment regimen. ;Its incidence was unrelated to that of candidiasis. The amount of oropharyngeal candidiasis on the other hand correlated strongly with the daily dose of budesonide and dosing frequency. B.i.d. treatment abolished the effect of increasing budesonide dose on candidiasis, and virtually eliminated any need for nystatin. A 24 h interval between doses (using an AM schedule), or two intervals of about 12 h were both effective in conserving antifungal host defences in the oropharynx. Temporary conversion to b.i.d. dosing can facilitate the control or prevention of thrush, especially when the risk is increased by concomitant antibiotic therapy, as was shown to be the case in these patients. A small, but statistically significant, deterioration in peak expiratory flow occurred during b.i.d. dosing. Thus, despite its ability to virtually eliminate the problem of recurring thrush, b.i.d. dosing should not be continued indefinitely. These considerations probably apply to other topically active steroids currently used to treat asthma.

Topics: Aerosols; Asthma; Budesonide; Candidiasis, Oral; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Pregnenediones; Voice Disorders

Budesonide, a topically active corticosteroid, was administered in doses of 400 and 1,600 micrograms/day to 35 asthmatic adults, using a standard inhalation device or a tube or cone spacer. The spacers reduced oropharyngeal candidiasis by an amount equivalent to a 90% reduction in drug dose (p = less than 0.005) and doubled the drug's overall antiasthmatic potency (delta FEV1, p = 0.05) without significantly increasing its overall effect on blood eosinophils (p = 0.14) or the A.M. serum cortisol (p = 0.12). Steroid-induced neutrophilia increased by an amount approximating that produced by an extra half tablet of prednisone per day (p = 0.002). Both the airways and systemic effects of the spacers were greater in patients who had small airways dysfunction present prior to the study. The data suggest an increase in intrapulmonary drug deposition during spacer treatment without a material shift in regional delivery within the lung. Spacers should be particularly useful for patients whose response to inhaled steroid is compromised by by dose-limiting oropharyngeal complications. They can also reduce drug costs. They should be used selectively in children until their effect on regional intrapulmonary drug deposition has been more clearly defined.

Topics: Administration, Topical; Aerosols; Anti-Inflammatory Agents; Asthma; Budesonide; Candida; Candidiasis, Oral; Dose-Response Relationship, Drug; Female; Glucocorticoids; Humans; Male; Middle Aged; Oropharynx; Pregnenediones; Respiratory Function Tests