DENTAL CARE
Adverse events with transmucosal buprenorphine products
The FDA is warning of dental issues associated with the use of transmucosal buprenorphine products, even in patients with no prior history of dental issues.
Buprenorphine is an opioid that was originally approved in 2002 as a sublingual tablet to treat opioid use disorder and pain. In 2015, the FDA approved a buccal film. Other forms exist, but these two are the only ones associated with the development of dental adverse events, said the FDA.
Patients have reported dental problems such as tooth decay, cavities, dental abscesses and infection, tooth erosion, and, total tooth loss in some cases.
The FDA says it is unable to determine the likelihood of any patient experiencing dental problems when taking transmucosal buprenorphine, though they do say the benefits of taking the medications outweigh the risks. Regular adherence to the medication reduces withdrawal symptoms and decreases the desire to further use opioids by decreasing pleasurable effects. The FDA says the comprehensive approach to treatment with buprenorphine and behavioral therapies sustains recovery, prevents or reduces opioid overdose, improves patient survival, and allows patients to live self-directed lives.
A new warning about the risks of dental issues will be required in the prescribing information and patient medication guide for all transmucosal buprenorphine-containing medications, the FDA says.
To reduce the risk of dental decay, the FDA advises patients to swish a sip of water between the teeth and gums after the product has dissolved. Patients should wait at least 1 hour before brushing their teeth and visit a dentist regularly to develop a preventive strategy, for close monitoring, and regular checkups.
The FDA suggests prescribers advise patients to see a dentist soon after starting treatment with a transmucosal buprenorphine product and patients report all medications they are taking to their provider.
Reference:
Center for Drug Evaluation and Research. FDA warns about risks of dental problems associated with buprenorphine. U.S. Food and Drug Administration. 2022. http://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-risks-dent.
COMMUNITY-ACQUIRED PNEUMONIA
Shorter antibiotic treatment for children
A 5-day antibiotic strategy may be superior to a 10-day strategy in children responding to initial treatment of outpatient community-acquired pneumonia (CAP) according to a study published in JAMA Pediatrics.1
Between December of 2016 and December of 2019, 380 children between the ages of 6 to 71 months with nonsevere CAP demonstrating early clinical improvement were enrolled in a randomized double-blind placebo-controlled clinical trial in outpatient clinics, urgent care centers, or emergency settings in eight US cities.
On the sixth day of prescribed therapy, each child was randomized to receive either 5 days of a matching placebo (n = 189) or 5 additional days of the same antibiotic (n = 191). Eight children were Asian, 99 Black American, 234 White American, 32 multiracial, and 7 were of unknown or unreported race; 33 were Hispanic, 344 were not Hispanic, and 3 were of unknown or unreported ethnicity. Just over half, 194 (51%) of the participants were male.
Researchers found that the short-course (5-day) strategy had a 69% probability of a more desirable response adjusted for duration of antibiotic risk when compared with the standard-course strategy.
Some children (n = 171) were also selected for throat swab collection between days 19 and 25 to quantify antibiotic resistance genes in oropharyngeal flora. The median number of antibiotic resistance genes per prokaryotic cell (RGPC) was significantly lower in the short-course strategy compared with standard-course strategy and beta-lactamase RGPC.
Overall, the shorter strategy achieved similar clinical responses and antibiotic-associated adverse events to the standard therapy while also reducing antibiotic exposure and resistance.
CAP is defined as signs and symptoms of an acute infection of the pulmonary parenchyma in a patient who acquired the infection in the community, as distinguished from hospital-acquired pneumonia. CAP can be caused by coronaviruses, respiratory syncytial virus, adenoviruses, influenza viruses, metapneumovirus, and parainfluenza viruses.2
Symptoms of CAP include malaise, chills, rigor, fever, cough, dyspnea (usually mild and exertional), and chest pain. Coughs are productive in older children, while dry in infants and young children. Given that some symptoms overlap, no symptom is sensitive nor specific enough to predict a particular organism.2
References:
1. Williams DJ, Creech CB, Walter EB, et al Short- vs standard-course outpatient antibiotic therapy for community-acquired pneumonia in children: the SCOUT-CAP randomized clinical trial. JAMA Pediatr. 2022. doi:10.1001/jamapediatrics.2021.5547. [Context Link]
2. Sethi S. Community-acquired pneumonia - pulmonary disorders. Merck Manuals Professional Edition. 2020. http://www.merckmanuals.com/professional/pulmonary-disorders/pneumonia/community. [Context Link]
BRAIN TUMOR
Risk linked with common hormone drug
High doses of cyproterone acetate (CPA) have been linked to an increased risk of meningiomas in a new study published in Scientific Reports.
CPA is a steroid ester used in high doses (greater than 50 mg per day) to treat hormonal disorders such as excessive hair growth, early puberty, and prostate cancer.1 The drug is also used at lower doses in combination with estradiol to treat androgen-associated alopecia or female seborrhoea.
Researchers at the University of Bristol, Cambridge, and the National University of Singapore conducted a meta-analysis of four retrospective observational studies examining meningioma development in conjunction with CPA use.2
Out of the 8,132,348 patients included in their meta-analysis, 165,988 received CPA. Throughout the studies observed, females received low doses of 2 mg per day, whereas all males received at least 50 mg per day.
Meningioma development was observed in patients older than 45 years (403 out of 456 (88.4%)). All studies that analyzed high versus low dose CPA found a significant association between high dose CPA usage and increased risk of meningioma.
The authors concluded that high dose CPA usage (greater than 50 mg per day) carries a significant risk for the development of meningiomas.
References:
1. NIH. Cyproterone acetate. National Center for Biotechnology Information. PubChem Compound Database. https://pubchem.ncbi.nlm.nih.gov/compound/Cyproterone-acetate. [Context Link]
2. Lee KS, Zhang JJ, Kirollos R, et al A systematic review and meta-analysis of the association between cyproterone acetate and intracranial meningiomas. Scientific Reports. 2022;12(1). doi:10.1038/s41598-022-05773-z [Context Link]
HEARING HEALTH
OTC analgesics associated with tinnitus
Frequent use of NSAIDs or acetaminophen, or regular use of COX-2 inhibitors, has been associated with a greater risk of tinnitus, according to a recent study published in the Journal of General Internal Medicine.
Researchers at Brigham and Women's Hospital in Boston, Mass. conducted a longitudinal cohort study that included about 70,000 women between the ages of 31 and 48 without tinnitus at baseline. The researchers sought self-reported information on analgesic use and tinnitus collected through biennial questionnaires.1
Frequent use was defined as use at least 6 out of 7 days per week. 10,452 cases of incident persistent tinnitus were reported in 1,120,936 follow-ups after one year.
Those consuming low-dose aspirin did not have an elevated risk of developing persistent tinnitus, the researchers said. However, an increased risk of persistent tinnitus development was recorded among those women taking a moderate dose of aspirin and who were younger than 60 years.
The researchers concluded that frequent use of moderate-dose aspirin elevated the risk of developing persistent tinnitus in women younger than 60 years by about 20%.
Limitations of the study included the fact that usages were self-reported, indications for analgesic use were not available, and studies in non-White women and men are needed.
Reference:
Curhan SG, Glicksman J, Wang M, et al Longitudinal Study of analgesic use and risk of incident persistent tinnitus. Journal of General Internal Medicine. 2022. doi:10.1007/s11606-021-07349-5 [Context Link]
KIDNEY DISEASE
Dapagliflozin and CKD outcomes
Dapagliflozin, a medication prescribed for Type 2 diabetes, was shown to be safe and effective in reducing major adverse kidney outcomes in participants with chronic kidney disease (CKD) who were not prescribed mineralocorticoid receptor antagonists (MRAs, a type of diuretic like spironolactone) at baseline in a paper published in Kidney International Reports.
Participants with CKD (estimated glomerular filtration rate [eGFR] 25-75 mL/min/1.73 m2; urinary albumin-to-creatinine ratio 200-500 mg/g), with or without type 2 diabetes were 1:1 randomized to receive dapagliflozin 10 mg or placebo, once daily.
Out of 4,304 total trial participants, 229 received conventional MRAs at baseline (dapagliflozin n = 109, placebo n = 120). The primary outcome was consistent in participants prescribed and not prescribed MRAs (hazard ratio [HR] 0.76, 95% CI 0.40-1.4; and HR 0.60, 95% CI 0.50-0.72, P-interaction = 0.59, respectively). MRAs.
Similarly, hyperkalemia (HR 0.87, 95% CI 0.70-1.09) was consistent among those prescribed and not prescribed MRAs (HR 0.94, 95% CI 0.41-2.20; and HR 0.87, 95% CI 0.69-1.10, P-interaction = 0.96, respectively). MRA. Adverse events leading to discontinuation and serious reactions were similar between treatment groups regardless of baseline MRA prescription. The authors concluded that kidney protective effects of both dapagliflozin and MRAs may be complementary.
The authors acknowledged some limitations to the study. Few participants were treated with MRAs at baseline and the authors were unable to assess effective initiation of combination therapy because participants were on a stable dose of MRA before enrollment into the trial. "Mineralocorticoid receptor antagonists reduce albuminuria in patients with CKD, but clinical trials to establish their effects on major kidney outcomes were lacking until recently," the authors wrote.
Reference:
Provenzano M, Jongs N, Vart P, et al The kidney protective effects of the sodium-glucose cotransporter-2 inhibitor, dapagliflozin, are present in patients with CKD treated with mineralocorticoid receptor antagonists. Kidney Int Rep. 2021. doi:10.1016/j.ekir.2021.12.013.