[8] Common side effects of ritonavir include nausea, vomiting, loss of appetite, diarrhea, and numbness of the hands and feet.

[4][5][8] Though initially developed as an independent antiviral treatment, it is most commonly used as a pharmacokinetic enhancer, in order to increase the plasma concentrations of other antiretrovirals.

[22] In December 2021, the combination of nirmatrelvir and ritonavir was granted emergency use authorization by the US Food and Drug Administration (FDA) for the treatment of coronavirus disease COVID-19.

[24][25][26] Paxlovid is not authorized for the pre-exposure or post-exposure prevention of COVID-19 or for initiation of treatment in those requiring hospitalization due to severe or critical COVID-19.

[24] On December 31, 2021, the UK Medicines and Healthcare products Regulatory Agency (MHRA) approved the same combination "for people with mild to moderate COVID-19 who are at high risk of developing severe COVID-19".

[30] Due to it being a strong inhibitor (that causes at least a five-fold increase in the plasma AUC values, or more than 80% decrease in clearance) of both cytochrome P450 enzymes CYP2D6 and CYP3A4, ritonavir can severely potentiate and prolong the half-life and/or increase the blood concentration of phenobarbital, primidone, carbamazepine, phenytoin, PDE5 inhibitors like sildenafil, opioids such as hydrocodone, oxycodone, pethidine and fentanyl, antiarrhythmic agents such as amiodarone, propafenone and disopyramide, immunosuppressants such as tacrolimus, voclosporin and sirolimus, neuroleptics like lurasidone and pimozide, as well as some chemotherapeutic agents, benzodiazepines and some ergot derivatives.

However, because of the general role of CYP3A4 in xenobiotic metabolism, dosing with ritonavir also affects the efficacy of numerous other medications, adding to the challenge of prescribing drugs concurrently.

[8] Ritonavir was demonstrated to have an in vitro potency of EC50=0.02 μM on HIV-1 protease and highly sustained concentration in plasma after oral administration in several species.

In the first step shown, an aldehyde derived from phenylalanine is treated with zinc dust in the presence of vanadium(III) chloride.

[10] After the start of the COVID pandemic in 2020, many antivirals, including protease inhibitors in general and ritonavir in particular, were repurposed in an effort to treat the new infection.

[45][46][47][48] Ritonavir serves to slow down metabolism of nirmatrelvir by cytochrome enzymes to maintain higher circulating concentrations of the main drug.

[49] In November that year, Pfizer announced positive phase 2/3 results, including 89% reduction in hospitalizations when given within three days after symptom onset.

[citation needed] It has been estimated that Abbott lost more than US$250 million as a result, and the incident is often cited as a high-profile example of disappearing polymorphs.

[55] The company's research and development teams ultimately solved the problem by replacing the capsule formulation with a refrigerated gelcap.[when?

][citation needed] In 2000, Abbott (now AbbVie) received FDA-approval for a tablet formulation of lopinavir/ritonavir (Kaletra) which contained a preparation of ritonavir that did not require refrigeration.