202205201345關於paxlovid- from 耶魯大學醫學院
13 Things To Know About Paxlovid, the Latest COVID-19 Pill
[最初發布：2022 年 3 月 10 日。更新：2022 年 5 月 12 日]
注意：本文中的信息在原始發佈時是準確的。由於有關 COVID-19 的信息變化迅速，我們鼓勵您訪問疾病控制與預防中心 (CDC)、世界衛生組織 (WHO) 以及您所在州和地方政府的網站以獲取最新信息。
Paxlovid 是最新的 COVID-19 治療方法，已成為新聞。該藥物於 12 月獲得美國食品和藥物管理局 (FDA) 的緊急使用授權 (EUA)，適用於任何 12 歲及以上體重至少 88 磅且有患嚴重疾病高風險的人。輝瑞公司最近開始在 6 至 17 歲的兒童和青少年中進行第 2 期和第 3 期試驗
這種由輝瑞公司開發的藥物有很多優點：在支持 EUA 的臨床試驗中，它的住院和死亡風險降低了 89%，這個數字足以促使美國國立衛生研究院 (NIH) ) 優先於其他 COVID-19 治療；它比許多其他 COVID-19 藥物便宜（在發生公共衛生緊急情況時由美國政府免費提供）；而且，也許最令人放心的是，它有望對抗 Omicron 變體。
“我認為這是‘改變遊戲規則’的開始，”耶魯大學醫學傳染病專家、醫學博士 Scott Roberts 說。“這確實是我們針對這種病毒的第一個有效的口服抗病毒藥丸。它顯示出明顯的好處，它確實可以防止高危人群住院和死亡。”
需要注意的是，Paxlovid（該藥物的品牌名稱，由兩種非專利藥物——nirmatrelvir 和 ritonavir 組成）並不是唯一可用於治療 COVID-19 的藥丸。FDA 還在 12 月向默克公司的一種名為 molnupiravir (Lagevrio) 的藥丸授予了 EUA，但一些研究表明，molnupiravir 只能將 COVID-19 住院和死亡的風險降低 30%。
就方便而言，這種藥物被認為是對瑞德西韋（2020 年 10 月 FDA 批准）等通過靜脈 (IV) 注射給藥的治療方法的改進。
我們向耶魯醫學傳染病專家詢問了有關 Paxlovid 的常見問題。以下是他們的回應。
1. Paxlovid 是如何工作的？
Paxlovid 是一種抗病毒療法，由包裝在一起的兩種獨立藥物組成。當您服用三片藥片時，其中兩片藥片將是 nirmatrelvir，一種抑制 SARS-CoV-2 蛋白複製的藥物。另一種是利托那韋，這種藥物曾經用於治療艾滋病毒/艾滋病，但現在用於提高抗病毒藥物的水平。
作為一種 COVID-19 治療藥物，利托那韋基本上會關閉 nirmatrelvir 在肝臟中的新陳代謝，因此它不會很快從您的身體中移出，這意味著它可以工作更長時間，從而有助於抵抗感染。
2. 我應該什麼時候服用 Paxlovid？
參與確定 COVID-19 治療方案的耶魯大學醫學傳染病專家 Jeffrey Topal 醫學博士說，與所有抗病毒藥物一樣，Paxlovid 在疾病早期發揮最佳作用——在這種情況下，在症狀出現的前五天內耶魯紐黑文醫院患者。
3. 我多久服用一次 Paxlovid？
您每天兩次服用三片 Paxlovid 藥片，持續五天，一個完整的療程，總計 30 片藥片。將藥丸包裝在“劑量卡”中很有幫助，基本上是一種藥物泡罩包裝，可讓您根據需要衝出藥丸。
4. Paxlovid 與達菲類似嗎？
達菲每天服用兩次，持續五天，必須在流感發作後 48 小時內開始服用。羅伯茨博士說：“當你給病人服用達菲時，它並沒有真正改變他們的流感病程。”
但 Topal 博士補充說，從研究方式開始，兩者之間也存在差異。研究人員表明，Paxlovid 可以預防住院和死亡。但由於流感導致的重症病例較少，臨床試驗的重點是達菲是否可以縮短流感病程——它確實做到了，他說。
5. 任何人都可以獲得 Paxlovid 處方嗎？
FDA 授權 Paxlovid 用於 12 歲及以上體重至少 88 磅的人。但為了有資格獲得處方，您還必須有 COVID-19 檢測結果呈陽性，並且患嚴重 COVID-19 的風險很高。
這意味著您必須要么患有某些潛在疾病（包括癌症、糖尿病、肥胖症或其他疾病），要么必須年滿 65 歲（超過 81% 的 COVID-19 死亡發生在該組中）。根據疾病預防控制中心的說法，一個人的基礎疾病越多，他們患上嚴重的 COVID-19 病例的風險就越高。
希望隨著時間的推移，對誰可以服用 Paxlovid 的限制將會放寬。FDA 於 12 月批准了 EUA，就在數量驚人的人感染了 Omicron 並且對護理的需求猛增，導致供應問題時。
6. Paxlovid 的效果如何？
在申請 FDA 授權時，輝瑞提供了 2021 年 7 月中旬至 12 月初進行的一項臨床試驗的數據。數據顯示，接受 Paxlovid 的參與者（所有人都未接種疫苗）患重病的可能性降低了 89%和接受安慰劑的試驗參與者相比死亡。（雖然建議在症狀出現後五天內服用 Paxlovid，但臨床試驗的參與者在三天內服用該藥物。）
7. 我們對 Paxlovid 在兒童中的作用了解多少？
輝瑞公司於 3 月啟動了一項臨床試驗，以研究 Paxlovid 在 6 至 17 歲的兒童和青少年中的安全性和有效性，這些兒童和青少年有 COVID-19 症狀並且病毒檢測呈陽性，並且既沒有住院也沒有患嚴重疾病的風險。
雖然 Paxlovid 被授權用於 12 歲及以上且體重至少 88 磅的青少年，但該年齡組並未在最初的臨床試驗中進行測試。但由於許多兒童體重達到 88 磅（被認為是成年人的體重），因此 FDA 允許在較年輕的人群中將 EUA 擴展用於單克隆抗體和瑞德西韋等藥物，Topal 博士補充道。
“根據 Paxlovid 中藥物的藥代動力學，這些藥物在這個年齡段的代謝和排泄——特別是肝和腎功能——的差異被認為與成年人相似，”Topal 博士說。
8. Paxlovid 對 Omicron 有效嗎？
Paxlovid 的臨床試驗是在 Omicron 成為主導之前進行的，但輝瑞公司表示該藥物可對抗高度傳染性的變體。三項基於實驗室的研究聲稱支持這一點——其中兩項研究由輝瑞公司進行，而第三項研究由輝瑞公司與西奈山伊坎醫學院合作完成。這些研究尚未在同行評審的醫學期刊上發表。
9. Paxlovid 的副作用是什麼？
羅伯茨博士解釋說，大多數服用 Paxlovid 的人不會出現嚴重的副作用。“Paxlovid 通常具有很好的耐受性，”他說。常見的副作用通常是輕微的，包括：
由於 Paxlovid 可被腎臟清除，因此輕度至中度腎病患者可能需要調整劑量，Dr. 博士解釋說。托帕爾。“對於患有嚴重腎病或正在接受透析的患者或患有嚴重肝病的患者，不建議使用 Paxlovid；藥物的含量可能會變得過高，並可能導致副作用增加，”他說。
值得注意的是，Paxlovid 仍在研究中，因此可能所有風險尚不清楚。（FDA 提供了一份關於 Paxlovid 的情況說明書，其中包含已知副作用的完整列表。）
10. 如果我正在服用其他藥物，我可以服用 Paxlovid 嗎？
Paxlovid 可能與一長串藥物相互作用，在某些情況下，醫生可能不會開 Paxlovid，因為這些相互作用可能會導致嚴重的並發症。
Paxlovid 與之相互作用的藥物清單包括移植患者服用的一些器官抗排斥藥物，以及更常見的藥物，如一些用於治療心律失常的藥物。Topal 博士解釋說，Paxlovid 還降低了許多老年人所依賴的抗凝劑或血液稀釋劑的新陳代謝，從而使體內這些藥物的水平升高到不安全的程度。
如果您懷孕或哺乳，FDA 建議與您的醫療保健提供者討論您的選擇和具體情況，因為在這些人群中沒有使用該藥物的經驗。如果您可能懷孕，建議您在服用 Paxlovid 時使用有效的屏障避孕或不進行性活動。
有報導稱，一些完成了五天 Paxlovid 療程的人的 COVID-19 症狀“反彈”；在這些情況下，症狀在完成治療後四五天再次出現。一些人還報告說在接受藥物治療後 COVID-19 檢測呈陽性。輝瑞曾表示，在 Paxlovid 的臨床試驗中，幾名參與者的病毒水平似乎“在第 10 天或第 14 天左右”出現反彈，儘管這也發生在一些服用安慰劑的人身上。
“這正在被密切調查，我們應該很快就會有更多的指導，”羅伯茨博士說。“假設是免疫系統沒有機會看到病毒的全部範圍，因為 Paxlovid 在疾病早期抑制了複製，”他說。
對於任何經歷反彈的人，輝瑞建議在其門戶網站上向他們報告與 Paxlovid 相關的不良事件。
12. 如果我不符合 Paxlovid 的條件，我還有什麼可以服用的嗎？
COVID-19 還有其他療法，任何不能服用 Paxlovid（可能是因為它會與另一種藥物相互作用）的人都應該與他們的醫生討論適合他們情況的最佳方法。
13. 如果 Paxlovid 可用，我是否仍需要“更新”疫苗接種？
即使您認為自己只是感冒或過敏，他也鼓勵您進行測試——如果您能得到一個。“家庭測試是真正‘實施’這些藥物的重要組成部分，”他說，並補充說，雖然家庭測試可能不像基於實驗室的聚合酶鏈反應 (PCR) 測試那樣高度敏感，但它們仍然非常敏感。有助於做出診斷。
Topal 博士說，人們還應該記住，Paxlovid 即使具有很高的功效，也並不完美，即使是完美的，病毒也會發生變異並對抗病毒藥物產生抗藥性。“有些人還會住院嗎？是的——沒有一種藥物是完美的，”他說。“但對於許多高危患者來說，這種藥物確實可以降低這種風險。”
如果您出現 COVID-19 的症狀並認為您有資格接受治療，您可以訪問政府的測試治療定位器。您可以使用該網站搜索您附近可以填寫 COVID-19 處方的地方，或確定提供檢測、醫療和 COVID-19 藥物的網站。
[Originally published: March 10, 2022. Updated: May 12, 2022]
Note: Information in this article was accurate at the time of original publication. Because information about COVID-19 changes rapidly, we encourage you to visit the websites of the Centers for Disease Control & Prevention (CDC), World Health Organization (WHO), and your state and local government for the latest information.
Paxlovid is the latest COVID-19 treatment that’s been all over the news. The drug was granted an emergency use authorization (EUA) by the Food and Drug Administration (FDA) in December for anyone ages 12 and older who weighs at least 88 pounds, and is at high risk for severe disease. Pfizer recently began Phase 2 and 3 trials in children and teens ages 6 to 17.
Paxlovid is an oral antiviral pill that can be taken at home to help keep high-risk patients from getting so sick that they need to be hospitalized. So, if you test positive for the coronavirus and a health care provider writes you a prescription, you can take pills at home and lower your risk of going to the hospital.
The drug, developed by Pfizer, has a lot of positives: It had an 89% reduction in the risk of hospitalization and death in the clinical trial that supported the EUA, a number that was high enough to prompt the National Institutes of Health (NIH) to prioritize it over other COVID-19 treatments; it’s cheaper than many other COVID-19 drugs (it’s provided for free by the U.S. government while there is a public health emergency); and, perhaps most reassuring, it is expected to work against the Omicron variant.
“I think it is the beginning of a ‘game-changer,’” says Scott Roberts, MD, a Yale Medicine infectious diseases specialist. “It's really our first efficacious oral antiviral pill for this virus. It shows clear benefit, and it really can prevent hospitalization and death in people who are at high risk.”
It’s important to note that Paxlovid (the brand name for the drug, which is made up of two generic medications—nirmatrelvir and ritonavir) isn’t the only pill available to treat COVID-19. The FDA also granted an EUA in December to a pill from Merck called molnupiravir (Lagevrio), but some studies suggest that molnupiravir has only a 30% reduction in the risk for hospitalization and death from COVID-19.
And as far as convenience, this medication is considered an improvement over treatments like remdesivir (approved by the FDA in October 2020), which is administered by intravenous (IV) injection.
We asked Yale Medicine infectious diseases experts common questions about Paxlovid. Below are their responses.
1. How does Paxlovid work?
Paxlovid is an antiviral therapy that consists of two separate medications packaged together. When you take your three-pill dose, two of those pills will be nirmatrelvir, the drug that inhibits the SARS-CoV-2 protein from replicating. The other is ritonavir, a drug that was once used to treat HIV/AIDS but is now used to boost levels of antiviral medicines.
As a COVID-19 treatment, ritonavir essentially shuts down nirmatrelvir’s metabolism in the liver, so that it doesn’t move out of your body as quickly, which means it can work longer—giving it a boost to help fight the infection.
2. When should I take Paxlovid?
You have to take Paxlovid within five days of developing symptoms.
Like all antivirals, Paxlovid works best early in the course of an illness—in this case, within the first five days of symptom onset, says Jeffrey Topal, MD, a Yale Medicine infectious diseases specialist who is involved in determining COVID-19 treatment protocols for Yale New Haven Hospital patients.
“Once you’ve been ill with the virus for more than a week, the damage done to the body in a severe case can’t be undone by the antiviral,” he says.
3. How often do I take Paxlovid?
You take three Paxlovid pills twice daily for five days for a full course that adds up to 30 pills. It helps that the pills are packaged in a “dose card,” basically a medication blister pack that allows you to punch out the pills as needed.
4. Is Paxlovid similar to Tamiflu?
“I think it's a good comparison,” says Dr. Roberts. Tamiflu is an antiviral drug that reduces flu symptoms. Both are prescription-only oral antiviral pills given early in illness.
Tamiflu is taken twice a day for five days, and it must be started within 48 hours of flu onset. “When you give a patient Tamiflu beyond that, it doesn’t really change the course of their flu,” Dr. Roberts says.
But there are also differences between the two, starting with the way they were studied, Dr. Topal adds. Researchers showed that Paxlovid can prevent hospitalization and death. But since influenza causes fewer severe cases, clinical trials focused on whether Tamiflu could shorten the length of flu illness—which it did, he says.
5. Can anyone get a Paxlovid prescription?
The FDA authorized Paxlovid for people ages 12 and older who weigh at least 88 pounds. But in order to qualify for a prescription, you must also have had a positive COVID-19 test result and be at high risk for developing severe COVID-19.
That means you must either have certain underlying conditions (including cancer, diabetes, obesity, or others) or be 65 or older (more than 81% of COVID-19 deaths occur in in this group). The more underlying medical conditions a person has, the higher their risk for developing a severe case of COVID-19, according to the CDC.
The hope is that the restrictions on who can take Paxlovid will be relaxed over time. The FDA granted the EUA in December, just as a staggering number of people were infected with Omicron and the need for care skyrocketed, leading to supply issues.
6. How well does Paxlovid work?
When it applied for FDA authorization, Pfizer presented data from a clinical trial conducted between mid-July and early December in 2021. The data showed that participants (all of whom were unvaccinated) who were given Paxlovid were 89% less likely to develop severe illness and death compared to trial participants who received a placebo. (While the recommendation is to take Paxlovid within five days of symptom onset, participants in the clinical trial took the drug within three days.)
Scientists will continue to study the drug’s effectiveness as it is used to treat patients in the real world.
7. What do we know about how Paxlovid works in kids?
Pfizer launched a clinical trial in March to study the safety and efficacy of Paxlovid in children and teenagers ages 6 to 17 who have COVID-19 symptoms and test positive for the virus, and who are neither hospitalized nor at risk for severe disease.
While Paxlovid is authorized for use in adolescents and teenagers ages 12 and up, and weighing at least 88 pounds, that age group wasn’t tested in the original clinical trial. But because many children reach 88 pounds—considered to be an adult weight—the FDA has allowed extensions of EUAs for medications such as monoclonal antibodies and remdesivir in younger age groups, adds Dr. Topal.
“Based on the pharmacokinetics of the drugs in Paxlovid, the differences in metabolism and excretion—liver and kidney function specifically—of these drugs in this age group are thought to be similar to that of adults,” Dr. Topal says.
8. Does Paxlovid work against Omicron?
Paxlovid’s clinical trials took place before Omicron became predominant, but Pfizer says the drug works against the highly contagious variant. Three laboratory-based studies claim to back this up—two of those studies were conducted by Pfizer, while the third was done by Pfizer in partnership with the Icahn School of Medicine at Mount Sinai. These studies have not yet been published in peer-reviewed medical journals.
9. What are the side effects from Paxlovid?
Most people who take Paxlovid should not experience serious side effects, explains Dr. Roberts. “Paxlovid is usually very well-tolerated,” he says. Common side effects, which are usually mild, include:
Altered or impaired sense of taste
Increased blood pressure
Since Paxlovid is cleared by the kidneys, dose adjustments may be required for patients with mild-to-moderate kidney disease, explains Dr. Topal. “For patients with severe kidney disease—or who are on dialysis—or those with severe liver disease, Paxlovid is not recommended; the levels of the drug can become too high and could cause increased side effects,” he says.
It’s worth noting that Paxlovid is still being studied, so it is possible that all of the risks are not yet known. (The FDA has provided a fact sheet on Paxlovid with a full list of known side effects.)
10. Can I take Paxlovid if I'm taking other medications?
There is a long list of medications Paxlovid may interact with, and in some cases, doctors may not prescribe Paxlovid because these interactions may cause serious complications.
The list of drugs that Paxlovid interacts with includes some organ anti-rejection drugs that transplant patients take, as well as more common drugs like some used to treat heart arrhythmias. Paxlovid also decreases the metabolism of anticoagulants, or blood thinners, that many older adults depend on, driving up levels of those medications in the body to a point where they are unsafe, Dr. Topal explains.
It also interacts with cholesterol-lowering medications like Lipitor, but that’s less challenging for patients to overcome. “If you stop taking your Lipitor for five days, nothing bad is going to happen,” he adds.
If you are pregnant or breastfeeding, the FDA recommends discussing your options and specific situation with your health care provider, since there is no experience using the drug in these populations. If you could become pregnant, it’s recommended that you use effective barrier contraception or do not have sexual activity while taking Paxlovid.
11. What is the rebound effect of Paxlovid?
There have been reports of a “rebound” of COVID-19 symptoms in some people who have completed the five-day course of Paxlovid; in those cases, symptoms have recurred four or five days after completing the treatment. Some have also reported having a positive COVID-19 test after being treated with the drug. Pfizer had said that in the clinical trial for Paxlovid, several participants appeared to have a rebound in virus levels “around day 10 or day 14,” although this also occurred in some people who were given a placebo.
“This is being closely investigated and we should have more guidance soon,” says Dr. Roberts. “The hypothesis is that the immune system didn’t have a chance to see the full extent of the virus, since Paxlovid suppressed replication early in disease,” he says.
There is currently no evidence to support a second course of Paxlovid in these situations, but scientists are studying the effects of longer treatment durations, longer periods of isolation, and other ways of managing the problem, he adds.
For anyone who experiences a rebound, Pfizer recommends reporting it to them on its portal for adverse events associated with Paxlovid.
12. If I'm not eligible for Paxlovid, is there something else I can take?
There are other therapies for COVID-19, and anyone who cannot take Paxlovid—perhaps because it would interact with another medication—should talk to their doctor about the best approach for their situation.
13. Do I still need to be 'up to date' on vaccination if Paxlovid is available?
Vaccination remains a key part of prevention, even as more drugs become available, says Dr. Topal. He pictures prevention as an upside-down pyramid. Vaccination, mitigation efforts, such as masking, and testing would be at the base—and medications at the top point.
“Early testing is key to making these drugs work,” he says. “It’s always been the Achilles’ heel of these antiviral drugs that most people don’t get tested—or they don’t have access to testing.”
He encourages taking a test even if you think you only have a cold or allergies—and if you can get one. “Home testing is a huge part of the way to really ‘operationalize’ these medications,” he says, adding that while home tests may not be as highly sensitive as the laboratory-based polymerase chain reaction (PCR) tests, they are still very helpful in making a diagnosis.
Dr. Topal says people also should remember that Paxlovid, even with its high efficacy, is not perfect, and even if it were, viruses can mutate and develop resistance to antiviral medications. “Will some people still be hospitalized? Yes—no medication is perfect,” he says. “But for many high-risk patients, this medication can really reduce that risk.”
If you are experiencing symptoms of COVID-19 and think you are eligible for a treatment, you can visit the government Test-to-Treat Locater. You can use the site to search for the places near you where you can fill a COVID-19 prescription, or identify sites that provide testing, medical care, and COVID-19 medications.
Information provided in Yale Medicine articles is for general informational purposes only. No content in the articles should ever be used as a substitute for medical advice from your doctor or other qualified clinician. Always seek the individual advice of your health care provider with any questions you have regarding a medical condition.