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 (last updated on May 17, 2021):
- Inhaled budesonide: The typical dose used for asthma and obstructive lung diseases is 180 to 360 micrograms inhaled twice a day, but effectiveness at these doses is not well-established. Based on the STOIC Trial (open label Phase 2), 800 micrograms inhaled twice a day shortened self reported time to recovery as well as the need for urgent care or hospital visits. Side effects were mild and self-limited and occurred among 5 subjects. With interim results from the PRINCIPLE Trial on budesonide 800micrograms twice a day, time to recovery in outpatients was reported to be reduced. Inhaled steroids are believed to reduce expression of cellular proteins that SARS-Cov2 must bind, and may explain why asthmatics did not have worse Covid19 outcomes than the general population, despite being initially anticipated. Cost may be a barrier for some patients in the US, including some insured patients whose plans favor alternate inhaled steroids that have not been tested in covid19.
Nitazoxanide: An antiparasitic drug typically used for infectious diarrhea, it is believed to interfere with multiple mechanisms of viral entry. Well-designed clinical trials have demonstrated its ability to reduce viral replication and accelerate time to viral clearance when used as early monotherapy, but its clinical benefits have not been well-established. It may be synergistic in multidrug regimens, including a combination with ivermectin, as shown in one trial where it was combined with ivermectin, ribavirin and zinc, in which 58% of treatment and zero controls cleared the virus by day 7 (p< 0.001). It has an extremely favorable safety profile and no contraindications in immunocompetent patients, but can be expensive in some cases.
- 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.
Recently added to our I-MASK+ and MATH+ protocols:
- Fluvoxamine: 50 mg PO twice daily for 10–14 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.
Recently added to our MATH+ protocol:
- Cyproheptadine: 6–8 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.
- Dutasteride: 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.