Dexamethasone Ophthalmic and Nirmatrelvir: Interaction Details

a) A 58-year-old man taking darunavir 800 mg/ritonavir 100 mg for HIV management was diagnosed with adrenal insufficiency, without preceding Cushing syndrome, 4 weeks after a local injection of triamcinolone 30 mg for relief of back pain. He presented with cold-like symptoms, progressive fatigue, muscular weakness, nausea, and a recent 3.5 kg weight loss; HIV viral load was less than 20 copies/mL and CD4 count was within normal limits. An adrenocorticotropic hormone (ACTH) test confirmed adrenal insufficiency. The patient was transitioned to an alternative HIV regimen devoid of ritonavir, and treatment with hydrocortisone was initiated at 35 mg/day with a 4 week taper. Symptoms improved rapidly and a follow up ACTH test after 4 weeks showed nearly complete resolution of adrenal insufficiency ³.

b) In a pharmacokinetic study in 18 subjects, coadministration of fluticasone propionate aqueous nasal spray 200 mcg once daily for 7 days concomitantly with ritonavir 100 mg every 12 hours for 7 days resulted in an approximate 350-fold increase in the fluticasone AUC and an approximate 25-fold increase in fluticasone Cmax. A decrease of 86% was also noted in plasma cortisol AUC. Systemic corticosteroid effects, including Cushing syndrome and adrenal suppression, have been reported during postmarketing use of ritonavir in combination with inhaled or intranasally administered fluticasone propionate or budesonide ⁴.

c) A 58-year-old, HIV-positive, African American woman had iatrogenic Cushing syndrome following concomitant administration of epidural triamcinolone and ritonavir. The woman had a history of spinal stenosis, hypertension, and hyperlipidemia. Her HIV regimen consisted of emtricitabine/tenofovir, ritonavir 100 mg, and fosamprenavir 1400 mg daily; other medications included hydroCHLOROthiazide 25 mg/day, omeprazole 40 mg/day, pravastatin 80 mg/day, and HYDROcodone/acetaminophen as needed. Four weeks after administration of epidural triamcinolone, she presented with generalized swelling (for 2 weeks), fatigue, profound weakness, dyspnea on exertion, tremor, insomnia, recent weight gain, and spinal stenosis. Physical examination revealed blood pressure of 199/89 mmHg (from a baseline of 110 to 120/70 to 80 mmHg), a temperature of 101.2 degrees F, and cushingoid facies and body habitus (eg, prominent dorsocervical hump and truncal obesity). Diffuse ecchymosis, pitting edema in the lower extremities, diaphoresis, and tremor were also noted. Her CD4 count was 150 (a decrease from 400 two months prior) and her baseline morning cortisol level was 0.9 mcg/dL. Cortisol levels rose slightly to 5.9 mcg/dL at 30 minutes and 8.1 mcg/dL at 60 minutes after receiving 250 mcg of IV cosyntropin, indicating suppression of the hypothalamic-pituitary-adrenal axis. Further corticosteroid injections were avoided and ritonavir was continued. At 6 weeks after discharge, swelling was significantly decreased, blood pressure returned to baseline, and the CD4 count increased to near baseline ⁵.

d) Ritonavir significantly increased the systemic exposure of prednisoLONE in a pharmacokinetic drug interaction study conducted in 10 HIV-seronegative, healthy volunteers. Each subject was given single oral doses of predniSONE 20 mg at baseline, and after receiving ritonavir 200 mg twice a day on days 4 and 14 of a 2-week course of ritonavir. Compared with baseline, the geometric mean prednisoLONE AUC increased from 2261 to 3098 nanograms (ng) x hr/mL (geometric mean ratios (GMR)=1.37; 90% CI, 1.27 to 1.47) and from 2261 to 2906 ng x hr/mL (GMR=1.28; 90% CI, 1.19 to 1.37) on days 4 and 14, respectively. PrednisoLONE apparent oral clearance (Cl/F) decreased from 9.84 L/hr at baseline to 6.45 L/hr (GMR=0.73; 90% CI, 0.68 to 0.78) on day 4 of ritonavir, and from 8.84 to 6.88 L/hr (GMR=0.78; 90% CI, 0.64 to 0.92) on day 14. PrednisoLONE half-life also increased from 2.96 hours at baseline to 3.92 hours on day 4 of ritonavir administration (GMR=1.33; 90% CI, 1.2 to 1.46). At day 14, there were no significant differences in prednisoLONE half-life compared with baseline. Cmax and Tmax were not significantly different between the groups (p greater than 0.05 for all comparisons) ⁶.