nitazoxanide + atazanavir + ritonavir

The combination of nitazoxanide + atazanavir + ritonavir is a repurposed drug therapy that has been investigated primarily for COVID-19 treatment. This combination brings together an antiprotozoal agent (nitazoxanide) with antiretroviral drugs (atazanavir/ritonavir) to potentially enhance antiviral effects. ## Pharmacological Properties Nitazoxanide is a broad-spectrum antiparasitic and antiviral agent that works by inhibiting pyruvate ferredoxin oxidoreductase (PFOR), an enzyme essential for anaerobic energy metabolism in parasites[6][10]. It has established efficacy against parasites like Cryptosporidium parvum and Giardia lamblia[8]. Atazanavir is an HIV protease inhibitor, while ritonavir serves as a pharmacokinetic enhancer. When combined with nitazoxanide, atazanavir/ritonavir significantly increases the plasma exposure of tizoxanide (nitazoxanide's active metabolite) by approximately 68-87%[2][4]. Specifically, the geometric mean ratios of tizoxanide AUC0-12h, Cmax, and C12h were 1.872, 2.029, and 3.14 respectively when co-administered with atazanavir/ritonavir[4]. ## Clinical Investigation The NACOVID trial investigated this combination for COVID-19 treatment in Nigeria. In this pilot, randomized, open-label trial, patients with mild to moderate COVID-19 received either standard of care (SoC) or SoC plus a 14-day course of nitazoxanide (1000 mg twice daily) and atazanavir/ritonavir (300/100 mg once daily)[2]. The trial results showed: - No significant difference in time to clinical improvement between the standard of care group and the intervention group (adjusted hazard ratio = 0.898, 95% CI: 0.492-1.638, p = 0.725)[2] - No difference in SARS-CoV-2 viral load changes from days 2 to 28 between the two arms (adjusted hazard ratio = 0.948, 95% CI: 0.341-2.636, p = 0.919)[2] - No significant difference in time from enrollment to complete symptom resolution (adjusted hazard ratio = 0.535, 95% CI: 0.251-1.140, p = 0.105)[2] Despite these results, the pharmacokinetic interaction between the drugs was notable, with atazanavir/ritonavir increasing tizoxanide plasma exposure by 68% and achieving median trough plasma concentrations of 1546 ng/ml (95% CI: 797-2557), which was above its putative EC90 in 54% of patients[2]. This combination represents an interesting approach to drug repurposing for viral infections, leveraging pharmacokinetic interactions to potentially enhance therapeutic effects, though clinical efficacy for COVID-19 was not demonstrated in the initial trials.

Other names

Nitazoxanide Plus Atazanavir/RitonavirNitazoxanide + Atazanavir + Ritonavir