Optional Medicines for the Treatment of COVID-19
A founding principle underlying our I-MASK+ and MATH+ treatment protocols is that they evolve in accordance with both emerging therapeutic trials evidence as well as new pathophysiologic insights. When sufficient supportive evidence for a new therapeutic against COVID-19 emerges, we first add these medicines as “optional” components until such a time when we can better clarify their additive or synergistic efficacy to the existing core therapies.
The most compelling recent therapeutic evidence suggests a role for the following therapies:
- Fluvoxamine: 50 mg PO BID for 14 days. Selective serotonin reuptake inhibitor (SSRI) that activates sigma-1 receptors decreasing cytokine production. Two randomized controls trials have found decreased risk of hospitalization and time to clinical recovery. Larger trials are ongoing.
- Cyproheptadine: 6 mg PO TID, monitor for drowsiness. Mounting evidence has identified the clear pathophysiologic role of excess platelet activation with serotonin release in COVID-19, thus explaining multiple physiologic abnormalties observed (hyperpnea, pulmonary vasodilation, renal vasoconstriction, neurologic dysfunction etc) which often quickly reverse in the presence of the anti-serotonin agent cyproheptadine.
- Dulateride: Men who develop COVID-19 have a significantly worse outcome than women (independent of other risk factors). This effect may be mediated in part by testosterone. Testosterone increases the expression of the transmembrane protease, serine 2 (TMPRSS2) which is required for priming of the spike protein for cell fusion. The antiandrogens dutasteride 0.5 mg/day and proxalutamide 200 mg /day (NCT 04446429) have been demonstrated to reduce time to viral clearance, improve time to recovery and reduce hospitalization in men with COVID-19 in the outpatient setting. It should be noted that proxalutamide in not available in the USA.
- Colchicine: Early outpatient use only – 0.6 mg BID for 3 days then reduce to 0.6 mg daily for total of 30 days. In the COLCORONA study colchicine reduced the need for hospitalization (4.5 vs 5.7%) in high risk patients. The drug was associated with an increased risk of side effects most notably diarrhea and pulmonary embolism. It is unclear if colchicine has any benefit in patients receiving ivermectin and whether the addition of colchicine to ivermectin has additive effects.