The combination of nirmatrelvir and ritonavir is used to treat coronavirus disease 2019 (COVID-19 infection) caused by the SARS-CoV-2 virus in adults and children 12 years of age and older who weigh at least 88 pounds (40 kg) who have mild to moderate symptoms and are at risk of severe disease that could result in hospitalization or death. Nirmatrelvir is in a class of medications called antivirals. It works by stopping the virus from spreading in the body. Ritonavir is in a class of medications called pharmacokinetic boosters. It works by increasing the amount of nirmatrelvir available in the body so that the medication will have a greater effect.

The combination of nirmatrelvir and ritonavir comes as tablets to be taken by mouth. The nirmatrelvir and ritonavir must be taken together for the medication to work correctly. It is usually taken with or without food two times a day for 5 days. Take nirmatrelvir and ritonavir at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take nirmatrelvir and ritonavir exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the tablets whole; do not split, chew, or crush them.

Take nirmatrelvir and ritonavir until you finish the prescription, even if you start to feel better. Do not stop taking nirmatrelvir and ritonavir without talking to your doctor. If you stop taking nirmatrelvir and ritonavir too soon or skip doses, your infection may not be completely treated.

Ask your pharmacist or doctor for a copy of the manufacturer’s information for the patient.

Before taking nirmatrelvir and ritonavir,

• Tell your doctor and pharmacist if you are allergic to nirmatrelvir, ritonavir, any other medications, or any of the ingredients in nirmatrelvir or ritonavir tablets. Ask your pharmacist for a list of the ingredients.
• Tell your doctor if you are taking alfuzosin (Uroxatral), amiodarone (Pacerone), apalutamide (Erleada), carbamazepine (Carbatrol, Epitol, Tegretol, Tegretol XR, others), clozapine (Clozaril), colchicine, dihydroergotamine (DHEA), dronedarone (Multaq), ergotamine, flecainide (Tambocor), lovastatin (Altoprev), lurasidone (Latuda), methylergonovine, midazolam (Nayzilam, Seizalam), phenobarbital, phenytoin (Dilantin, Phenytek), pimozide (Orap), piroxicam (Feldene), propafenone (Rythmol), quinidine, ranolazine (Ranexa), rifampin (Rifadin, Rimactane, in Rifamate, Rifater), sildenafil (Revatio), simvastatin (Flolipid, Zocor, in Vytorin), St. John’s wort,or triazolam (Halcion). Your doctor may tell you not to take nirmatrelvir and ritonavir if you are taking one or more of these medications.
• Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: anticoagulants (‘blood thinners’) such as warfarin (Coumadin); atorvastatin (Lipitor, in Caduet); bosentan (Tracleer); bupropion (Aplenzin, Forfivo, Wellbutrin, in Contrave); calcium channel blockers such as amlodipine (Norvasc, in Caduet, in Tribenzor, others), diltiazem (Cardizem, Tiazac, others), felodipine, nicardipine, or nifedipine (Procardia); cyclosporine (Gengraf, Neoral, Sandimmune); digoxin (Lanoxin); encorafenib (Braftovi); ethinyl estradiol oral contraceptives such as certain (‘birth control pills’), patches, hormonal vaginal rings and other ethinyl estradiol products; fentanyl (Actiq, Fentora, Lazanda, Subsys); glecaprevir and pibrentasivir (Mavyret); ibrutinib (Imbruvica); ivosidenib (Tibsovo); methadone (Methadose); neratinib (Nerlynx); quetiapine (Seroquel); rifabutin (Mycobutin, in Talicia); rivaroxaban (Xarelto); rosuvastatin (Crestor, in Ezallor Sprinkle, in Roszet); salmeterol (Serevent, in Advair, in Airduo Respliclick, others); sirolimus (Rapamune); oral or inhaled steroids such as betamethasone, budesonide (Endocort, Ortikos, Pulmicort, Rhinocort, others), ciclesonide (Alvesco, Omnaris, Zetonna), dexamethasone, fluticasone (Flonase, Flovent, in Advair, in Breo Ellipta, others), methylprednisolone (Medrol). mometasone (Asmanex, in Dulera). prednisone, and triamcinolone; tacrolimus (Astagraf, Prograf); trazodone; venetoclax (Venclexta): and voriconazole (Vfend). Your doctor may need to change the doses of your medications or monitor you carefully for side effects. Many other medications may also interact with nirmatrelvir and ritonavir, so be sure to tell your doctor about all the medications you are taking, even those that do not appear on this list.
• If you are taking a ritonavir- or cobicistat-containing medicine to treat hepatitis C or human immunodeficiency virus (HIV), you should continue to take these medications as prescribed while taking nirmatrelvir and ritonavir.
• Tell your doctor if you have or have ever had HIV, kidney disease, or liver disease.
• Tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking nirmatrelvir and ritonavir, call your doctor.
• You should know that nirmatrelvir and ritonavir may decrease the effectiveness of hormonal contraceptives (birth control pills, patches, rings, implants, injections, and intrauterine devices). Use another form of birth control or do not have sexual intercourse while you are taking nirmatrelvir and ritonavir. Talk to your doctor about types of birth control that will work for you during your treatment with nirmatrelvir and ritonavir.

Unless your doctor tells you otherwise, continue your normal diet.

If you miss a dose within 8 hours of the time it is usually taken, take the missed dose as soon as you remember it. However, if you miss a dose by more than 8 hours, skip the missed dose and continue your regular dosing schedule. Do not take a double dose to make up for a missed one.

Nirmatrelvir and ritonavir may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• Altered taste
• Diarrhea
• Muscle aches

Some side effects can be serious. If you experience any of these symptoms, stop taking nirmatrelvir and ritonavir and call your doctor immediately:

• Loss of appetite
• Yellowing of your skin or the whites of your eyes
• Dark-colored urine
• Pale-colored stools
• Itchy skin
• Stomach pain

Nirmatrelvir and ritonavir may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA’s Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

In case of overdose, call the poison control helpline at 1-800-222-1222. Information is also available online at https://www.poisonhelp.org/help. If the victim has collapsed, had a seizure, has trouble breathing, or can’t be awakened, immediately call emergency services at 911.

Keep all appointments with your doctor.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

Tell your healthcare provider if you do not feel better or if you feel worse after 5 days.

You should continue to isolate as directed by your doctor and follow public health practices such as wearing a mask, social distancing, and frequent hand washing.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

The American Society of Health-System Pharmacists, Inc. represents that this information about nirmatrelvir and ritonavir was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are cautioned that nirmatrelvir and ritonavir are not approved for treatment of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, but rather, are being investigated for and are currently available under, an FDA emergency use authorization (EUA) for the treatment of COVID-19 in certain adults and children 12 years of age and older. The American Society of Health-System Pharmacists, Inc. makes no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to the information, and specifically disclaims all such warranties. Readers of the information about nirmatrelvir and ritonavir are advised that ASHP is not responsible for the continued currency of the information, for any errors or omissions, and/or for any consequences arising from the use of this information. Readers are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information contained in this information is provided for informational purposes only. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. This information about nirmatrelvir and ritonavir are not to be considered individual patient advice. Because of the changing nature of drug information, you are advised to consult with your physician or pharmacist about specific clinical use of any and all medications.