The US Food and Drug Administration (FDA) approved ritonavir on March 1, 1996, As a result of the introduction of "highly active antiretroviral thearap[ies]" the annual U.S. HIV-associated death rate fell from over 50,000 to about 18,000 over a period of two years.In 2014, the FDA approved a combination of ombitasvir/paritaprevir/ritonavir for the treatment of hepatitis C virus (HCV) genotype 4.In 2021, a combination of ritonavir with nirmatrelvir, an orally active 3C-like protease inhibitor, was developed for the treatment of COVID-19. Ritonavir serves to slow down metabolism of nirmatrelvir by cytochrome enzymes to maintain higher circulating concentrations of the main drug. In November that year, Pfizer announced positive phase 2/3 results, including 89% reduction in hospitalizations when given within three days after symptom onset. Polymorphism and temporary market withdrawal
Ritonavir was originally dispensed as a capsule that did not require refrigeration. This contained a crystal form of ritonavir that is now called form I. However, like many drugs, crystalline ritonavir can exhibit polymorphism, i.e., the same molecule can crystallize into more than one crystal type, or polymorph, each of which contains the same repeating molecule but in different crystal packings/arrangements. The solubility and hence the bioavailability can vary in the different arrangements, and this was observed for forms I and II of ritonavir.During development—ritonavir was introduced in 1996—only the crystal form now called form I was found; however, in 1998, a lower free energy, more stable polymorph, form II, was discovered. This more stable crystal form was less soluble, which resulted in significantly lower bioavailability.
Tolterodine, sold under the brand name Detrol among others, is a medication used to treat frequent urination, urinary incontinence, or urinary urgency. Effects are seen within an hour. It is taken by mouth.Common side effects include headache, dry mouth, constipation, and dizziness. Serious side effects may include angioedema, urinary retention, and QT prolongation. Use in pregnancy and breastfeeding are of unclear safety. It works by blocking muscarinic receptors in the bladder thus decreasing bladder contractions.Tolterodine was approved for medical use in 1998. It is available as a generic medication. In 2019, it was the 292nd most commonly prescribed medication in the United States, with more than 1 million prescriptions. Medical uses
Detrusor overactivity (DO, contraction of the muscular bladder wall) is the most common form of urinary incontinence (UI) in older adults. It is characterized by uninhibited bladder contractions causing an uncontrollable urge to void. Urinary frequency, urge incontinence and nocturnal incontinence occur. Abnormal bladder contractions that coincide with the urge to void can be measured by urodynamic studies. Treatment is bladder retraining, pelvic floor therapy or with drugs that inhibit bladder contractions such as oxybutynin and tolterodine. Side effects
Known side effects:

Dry mouth
Decreased gastric motility (upset stomach)
Headache
Constipation
Dry eyes
Sleepiness
Urinary retentionThe following reactions have been reported in people who have taken tolterodine since it has become available:

Allergic reactions including swelling
Rapid heartbeat or abnormal heartbeat
Accumulation of fluid in the arms and legs
HallucinationsTolterodine is not recommended for use in people with myasthenia gravis and angle closure glaucoma.