New COVID-19 pills carry risks: What patients need to know

In December, the Food and Drug Administration, along with Merck & Co., its partners Ridgeback Biotherapeutics, and Pfizer Inc., authorized the use of new pills to treat mild to moderate COVID-19 in people with severe deteriorating conditions. are at high risk of. Diseases, such as the elderly or those with certain chronic medical conditions.

Both drugs, which must be prescribed by a doctor, are five-day regimens that must be started within five days of symptom onset. The drugs work by blocking the replication of the pandemic virus, and clinical trials have shown that they reduce the risk of hospitalization and death in people with mild to moderate COVID-19.

Health officials and drug makers say the benefits of the pills far outweigh the risks. They may be particularly useful as the Omron coronavirus variant spreads as some other COVID-19 treatments have been shown to lose effectiveness against the variant. The new pills are not expected to lose effectiveness against Omicron because they target parts of the virus that are not significantly mutated into the different forms.

“I think they’re likely to be an incredibly important tool to prevent hospitalizations,” said Dr. Rajesh Gandhi, an infectious disease specialist at Massachusetts General Hospital in Boston.

But not everyone infected with Kovid-19 is a candidate for treatment. The Pfizer drug, Paxlovid, should not be used at the same time as certain other medicines, including generic medicines such as the cholesterol-lowering pill simvastatin, also known by the brand Zocor.

This is because a component of paxlovid, an older booster agent called ritonavir, can interact with other drugs in dangerous and life-threatening ways. Doctors say that in some cases it may be possible to suspend the use of another drug or adjust its dosage over the course of five days.

“Patients and physicians need to know how to investigate drug interactions,” said Dr. Gandhi, who is also a professor of medicine at Harvard Medical School. Patients should make sure that they tell the doctor or pharmacist about any other medicines they take, including over-the-counter medicines and herbal products.

The Paxlovid interaction problem results from ritonavir’s inhibition of a naturally occurring enzyme in the body called CYP3A. While this helps improve the effectiveness of Paxlovid, the CYP3A enzyme is also responsible for the metabolism of many other drugs. If a person is taking another drug that is highly dependent on CYP3A for clearance from the body, taking Paxlovid at the same time can lead to a dangerous build-up of higher-than-normal concentrations of the other drug.

The FDA-authorized fact sheet for Paxlovid lists several drugs that should not be taken with Paxlovid because of CYP3A interactions.

In addition to simvastatin, they include some antipsychotics, analgesics, and the herbal product St. John’s wort. Some other drugs may be co-administered with Paxlovid, but with dosage adjustments to ensure safety.

Many infectious disease doctors have become accustomed to ritonavir drug-interaction issue because it has been a standard part of HIV treatment for years.

An infectious-disease physician at Yale Medicine in New Haven, Conn. Jamie Meyer said it should be manageable to reduce the dose or temporarily stop treatment with some other medication, especially since the PaxLovid regimen is only five days long.

“Sometimes we choose different drugs” that don’t have an interaction with ritonavir, said Dr. Meyer, who works in the HIV clinic in addition to her role as an associate professor at Yale School of Medicine.

Paxlovid is approved for use in people 12 years of age and older who are infected and at high risk of worsening severe COVID-19. The drug reduced the risk of Covid hospitalization and death from any cause by 88% in clinical trials. There were some side effects, including taste disorders, diarrhea, high blood pressure and muscle pain, but they occurred at relatively low rates.

James Rusnack, chief development office of Pfizer’s internal medicine and hospital division, said on a recent conference call with analysts, “We believe that related drug-drug interactions can be managed clinically, especially with five- days for a short period of time.” ,

The second antiviral the FDA recently approved, mollupiravir from Merck and Ridgeback, was less effective than Pfizer in clinical trials, reducing people’s risk of hospitalization or death by 30%. Side effects, including diarrhea and dizziness, were relatively rare.

The FDA said adults should only take Merck medication if they do not have access to other treatments, or if they are not able to take other treatments.

Thus, some people who should not take Pfizer’s paxlovid because of potential drug-drug interactions may be candidates for the Merck drug. Merck medicine has no known interactions with other drugs that would limit its use.

But the Merck drug also has safety considerations. It is authorized for adults, but not for children under the age of 18, because of its potential effect on bone and cartilage development. High doses of the drug impaired bone and cartilage growth in rat studies.

The drug Merck is not recommended for pregnant women because of the potential for fetal harm, a safety indication seen in animal studies of the drug.

And the FDA says women of childbearing age should use reliable contraception during treatment and for four days after the last dose. Men who are sexually active with women of childbearing potential should use contraception during treatment and for at least three months after the last dose.

The way Merck’s drug works has also raised concerns about its effects. It is designed to block the replication of the COVID-19 coronavirus by causing a genetic mutation in the virus. This has raised concerns that it could lead to forms of the virus developing in patients taking the drug, which could then survive and be transmitted to others. FDA officials said the drug lowers the viral load, and patients must self-isolate during treatment, which could reduce this potential risk of transmitting a variant. A Merck spokesman said there was no evidence the drug contributed to the emergence of circulating forms.

The mechanism of Merck’s drug has also raised concerns that it could cause genetic changes in patients. The FDA concluded that this risk is low, partly due to the short duration of treatment. A Merck spokesperson said animal studies indicated that mollupiravir did not cause mutations or damage to DNA in animals.

Merck said its safety analysis supports the short-term use of molnupiravir in adults.