From 1 May 2022, Paxlovid™ will be available on the Pharmaceutical Benefits Scheme (PBS). This will be the second oral agent PBS-listed for the treatment of COVID-19. Paxlovid™ is provisionally approved for the treatment of COVID-19 in adults who do not require initiation of supplemental oxygen but are at increased risk of progression to hospitalisation or death.
Paxlovid™ contains nirmatrelvir co-packaged with ritonavir. Nirmatrlevir inhibits the main protease of the SARS-CoV-2 virus, an enzyme with a key role in viral replication. To increase plasma levels of this antiviral, it is taken with ritonavir, a strong inhibitor of cytochrome P450 3A4. The recommended dose is two nirmatrelvir tablets and one ritonavir tablet taken together every 12 hours for five days. Therapy should be initiated as soon as possible after a diagnosis of COVID-19 and within five days of symptom onset.
The efficacy of nirmatrelvir and ritonavir was investigated in the EPIC-HR Study. An interim analysis of patients treated within three days of symptom onset showed a reduction in the incidence of COVID-19-related hospitalisation compared to placebo. At day 28, the incidence of hospitalisation was 0.77% in the nirmatrelvir and ritonavir group and 7.01% in the placebo group. There were no deaths in the treatment group and seven in the placebo group.
Paxlovid™ has many clinically significant drug interactions due to its effect on cytochrome P450. It is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated levels are associated with serious reactions. It is also contraindicated with potent CYP3A inducers where significantly reduced levels of nirmatrelvir or ritonavir may lead to loss of efficacy and resistance. A summary of contraindicated medicines is shown in Table 1. Refer to the product information for complete details.
Table 1. Medications contraindicated with Paxlovid™
|Apalutamide, neratinib, venetoclax
|HMG-CoA reductase inhibitors
|Avanafil, sildenafil, vardenafil, tadalafil
|Carbamazepine, phenobarbital, phenytoin
|St. John’s Wort
The COVID-19 Clinical Evidence Taskforce publishes recommendations on a range of COVID-19 therapies. The relative effectiveness of these therapies is currently unclear.
- Hammond J, Leister-Tebbe H, Gardner A, Abreu , Bao W, Wisemandle W, et al. Oral nirmatrelvir for high-risk, nonhospitalized adults with Covid-19. N Engl J Med. 2022; 386: 1397-1408.
- Paxlovid™ (nirmatrelvir/ritonavir) Australian approved product information. Sydney: Pfizer Australia. Approved January 2022.
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