Real-World Adherence to Toxicity Management Guidelines for Immune-Related Adverse Events.

Immune checkpoint inhibitors (ICIs) affect immunologic homeostasis, leading to immune-related adverse events (irAEs). Early irAE detection and management can prevent significant morbidity and mortality. A retrospective chart review was performed to characterize irAEs associated with nivolumab, ipilimumab, and nivolumab plus ipilimumab in adult medical oncology patients in Nova Scotia Health-Central Zone from 2013-2020, and to describe adherence to toxicity management guidelines. Diarrhea/colitis, hepatitis, pneumonitis, nephrotoxicity, and cardiotoxicity were studied. Of 129 charts reviewed, 67 patients (51.9%) experienced at least one irAE for a total of 98 irAEs and a 1.5% fatality rate. Of these irAEs, 33.7% led to an emergency room visit. Patients were admitted to hospital and steroids were used in 24.5% and 35.7% of cases, respectively. In 17.3% of irAEs, ICIs were permanently discontinued. In 20.4% of irAEs, ICIs were held, and patients were monitored; while in 18.4%, ICIs were held until the irAE was Grade 0-1 (and until steroids were tapered). Almost 47% of irAEs were managed according to guidelines (14.3% were not), and 38.8% had no documented management. Patients receiving immunotherapy frequently experience irAEs with half of irAEs having documented management adhering to guidelines. As immunotherapy indications expand, it is important to ensure irAEs are documented and managed appropriately.

Stability of Compounded Topical Nifedipine in Cream, Gel, and Ointment Bases.

The objective of this study was to investigate the stability of compounded nifedipine cream in gel and ointment formulations dispensed in white plastic and glass amber jars. Extemporaneously compounded nifedipine cream (Glaxal Base), gel (K-Y Jelly), and ointment (Aquaphor) in white plastic and glass amber jars were stored at 4°C, 23°C, and 40°C. We determined potency on days 0, 7, 14, 30, 60, and 90, and subsequently assigned beyond-use-dates based on United States Pharmacopeia recommendations, organoleptic properties, and pH changes. Nifedipine potency in cream and ointment stored in white plastic jars was within ±10% of initial for 90 days (excluding day 14 for cream). In glass amber jars, potency was outside the acceptable range by day 14 at 23°C but within range for 90 days at 4°C (excluding day 30). Nifedipine potency was maintained for 90 days in both jars at 23°C and 4°C (excluding day 30) and in white plastic jars at 40°C, but 60 days stored in glass amber jars. The pH of formulations was stable with changes of less than 1-unit pH. At 40°C, a significant decrease in apparent viscosity of cream was evident on day 90. There was a decrease in apparent viscosity and phase separation of the ointment at 40°C and an increase in apparent viscosity (difficult to mix) at 4°C on day 14 onwards. Significant organoleptic changes were observed by day 7 at 40°C (decrease in apparent viscosity and abnormal odor by day 90), day 30 at 4°C (thicker consistency), and day 90 at 23°C (abnormal odor). Storage in white plastic jars at 23°C is recommended for compounded topical nifedipine cream and ointment (for 90 days), and for gel (60 days).

Stability of Compounded Diltiazem Hydrochloride in Cream, Ointment, and Gel Formulations for Topical Use.

Interest in the topical use of compounded diltiazem has increased. Published information on the stability of such products is scarce. The objective of this study was to investigate the stability of diltiazem hydrochloride compounded in cream (Glaxal Base), ointment (white petrolatum), and hydroxyethyl cellulose-based gel over 90 days at room (23°C), refrigerator (4°C), and elevated (40°C) temperatures, stored in white plastic and glass amber containers. Organoleptic properties, pH changes, and United States Pharmacopeia recommendations were used for assigning beyond-use-dates. The results showed that the currently recommended United States Pharmacopeia beyond-use date of 30 days is acceptable for diltiazem (2%) in Glaxal Base at 4°C and 23°C in either white plastic or glass amber jars. The cream, however, is not recommended for use if exposed to elevated temperatures (40°C) in white plastic jars but may be used within 7 days if stored in glass amber jars. A beyond-use date of 90 days for diltiazem (2%) hydroxyethyl cellulose-based gel, when maintained at 4°C or 23°C, in either white plastic or glass amber jars, is recommended. Gels exposed to elevated temperatures (40°C) should be used within14 and 30 days in glass amber and white plastic jars, respectively. Lastly, a BUD of 90 days for diltiazem (2%) ointment (white petrolatum) at 23°C stored in either jar type is acceptable. Ointment formulations exposed to elevated temperatures (40°C) may be used within 7 days in white plastic jars. Diltiazem (2%) in white petrolatum should not be stored at 4°C.

Drug-release Assessment of Compounded Topical Nifedipine and Diltiazem in Commonly Used Bases for Wound Healing.

The objective of this study was to determine release profiles of extemporaneously compounded nifedipine and diltiazem in commonly used bases in pharmacy practice. Release of nifedipine 0.2%, 2%, and 10% (w/w) from Glaxal Base, K-Y Jelly, and Aquaphor Healing Ointment, and of diltiazem 2% (w/w) from GlaxalBase, hydroxyethyl cellulose-based gel, and white petrolatum was quantified using the Franz-cell diffusion system. The cumulative release was determined at 0.5 hour, 1 hour, 1.5 hours, 2 hours, 3 hours, 4 hours, and 6 hours. Two-way ANOVA with Tukey's posthoc test was used for statistical analyses, with a P-value of <0.05 considered significant. At a 0.2% concentration, cumulative nifedipine release was highest from Glaxal Base. At 2% and 10% concentrations, nifedipine release was highest from K-Y Jelly, although this was only significantly different from Glaxal Base at 6 hours and 1.5 hours, 4 hours, 6 hours (P<0.05), respectively. Diltiazem release from Glaxal Base and white petrolatum was significantly lower than the gel (P<0.05). No significant difference in diltiazem release from Glaxal Base at 0.5 hour was observed versus white petrolatum (P>0.05). Nifedipine and diltiazem release both followed Higuchi's mathematical model with the highest coefficient of determination (R2) for all formulations. Of the bases studies, Glaxal Base is the recommended base for compounding topical nifedipine (0.2%). For higher concentrations of nifedipine (2% and10%), both Glaxal Base and K-Y Jelly are suitable options for base selection. A hydroxyethylcellulose-based gel is recommended for topical diltiazem (2%).