Nirmatrelvir-Ritonavir

Nirmatrelvir/ritonavir is an investigational medication used for the treatment of COVID-19 disease.

• Nirmatrelvir/ritonavir is available under the following different brand names: Paxlovid

Common side effects of Nirmatrelvir/ritonavir include:

• diarrhea, 
• myalgia, 
• altered sense of taste, and 
• high blood pressure

Serious side effects of Nirmatrelvir/ritonavir include:

• hives, 
• difficulty breathing, 
• swelling of the face, lips, tongue, or throat, 
• severe dizziness, and
• abnormal lab test results

Rare side effects of Nirmatrelvir/ritonavir include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Tablets

• Dose pack 300 mg nirmatrelvir and 100 mg ritonavir: Each daily blister card contains 4 nirmatrelvir tablets (150-mg) and 2 ritonavir tablets (100-mg)
• Dose pack 150 mg nirmatrelvir and 100 mg ritonavir: Each daily blister card contains 2 nirmatrelvir tablets (150-mg) and 2 ritonavir tablets (100-mg)

COVID-19 Disease Treatment (Emergency use authorization)

Adult dosage

• 300 mg nirmatrelvir plus 100 mg ritonavir orally twice daily for 5 days
• Initiate as soon as possible after COVID-19 diagnosis and within 5 days of symptom onset
• Completing the full 5-day treatment course and isolating following public health recommendations are important to maximize viral clearance and minimize viral transmission

Pediatric dosage

• Aged below 12 years: Safety and efficacy not established
• 300 mg nirmatrelvir plus 100 mg ritonavir orally twice daily x 5 days

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Nirmatrelvir/ritonavir has severe interactions with at least 44 other drugs.
• Nirmatrelvir/ritonavir has serious interactions with at least 31 other drugs.
• Nirmatrelvir/ritonavir has moderate interactions with at least 70 other drugs.
• Nirmatrelvir/ritonavir has no noted minor interactions with the following drugs:
  • emtricitabine
  • irbesartan
  • losartan
  • macitentan
  • mycophenolate
  • sacubitril/valsartan
  • sofosbuvir/velpatasvir
  • valsartan

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• History of clinically significant hypersensitivity reactions (eg, toxic epidermal necrolysis [TEN], Stevens-Johnson syndrome [SJS]) to nirmatrelvir or ritonavir
• Drugs highly dependent on CYP3A for clearance
• Alpha1-adrenoreceptor antagonist: Alfuzosin
• Analgesics: Meperidine
• Antianginal: Ranolazine
• Antiarrhythmic: Amiodarone, dronedarone, flecainide, propafenone, quinidine
• Antigout: Colchicine
• Antipsychotics: Lurasidone, pimozide, clozapine
• BPH agents: Silodosin
• Cardiovascular agents: Eplerenone, ivabradine
• Ergot derivatives: Dihydroergotamine, ergotamine, methylergonovine
• HMG-CoA reductase inhibitors: Lovastatin, simvastatin
• Immunosuppressants: Voclosporin
• Microsomal triglyceride transfer protein inhibitor: Lomitapide
• Migraine medications: Eletriptan, ubrogepant
• Mineralocorticoid receptor antagonists: Finerenone
• Opioid antagonists: Naloxegol
• PDE5 inhibitor: Sildenafil (Revatio) when used for pulmonary arterial hypertension (PAH)
• Sedative/hypnotics: Triazolam, oral midazolam
• Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: Flibanserin
• Vasopressin receptor antagonists: Tolvaptan
• Drugs that are potent CYP3A inducers
• Anticancer drugs: Apalutamide
• Anticonvulsant: Carbamazepine, phenobarbital, primidone, phenytoin
• Antimycobacterials: Rifampin
• CFTR modulator: Lumacaftor/ivacaftor
• Herbal products: St. John’s Wort (Hypericum perforatum)

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Nirmatrelvir/ritonavir?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Nirmatrelvir/ritonavir?”

Cautions

• Hypersensitivity reactions reported including urticaria, angioedema, dyspnea, mild skin eruptions, and pruritus; cases of anaphylaxis; TEN, and SJS reported with ritonavir; if significant hypersensitivity reaction or anaphylaxis occurs, immediately discontinue and initiate appropriate medications and/or supportive care
• Hepatic transaminase elevations, clinical hepatitis, and jaundice reported with ritonavir; caution when administering to patients with preexisting liver diseases, liver enzyme abnormalities, or hepatitis
• Because nirmatrelvir is coadministered with ritonavir, possible risk of developing resistance to HIV protease inhibitors in individuals with uncontrolled or undiagnosed HIV-1 infection
• COVID-19 rebound
  • May 24, 2022: CDC has issued a health advisory regarding the potential for recurrence of COVID-19 or “viral RNA rebound” after case reports documented persons treated with nirmatrelvir/ritonavir and having recovered can experience recurrent illness
  • COVID-19 rebound is characterized by the reoccurrence of symptoms or a new positive viral test after having tested negative
  • Currently, there is no evidence that additional treatment is needed for COVID-19 rebound and patient monitoring continues to be the most appropriate management of symptom reoccurrence
• Persons with COVID-19 rebound should
  • Re-isolate for at least 5 days
  • Per CDC guidance, they can end their re-isolation period after 5 full days if the fever has resolved for 24 hr (without the use of antipyretics) and symptoms are improving
  • The patient should wear a mask for a total of 10 days after rebound symptoms started
  • Consider clinical evaluation of patients who have COVID-19 rebound and symptoms that persist or worsen
  • Healthcare workers are encouraged to report cases of COVID-19 rebound after Paxlovid treatment using Pfizer Safety Reporting or FDA MedWatch
• Drug interaction overview
  • Potential for nirmatrelvir and ritonavir to affect other drugs
  • Nirmatrelvir and ritonavir is an inhibitors of CYP3A and may increase drugs primarily metabolized by CYP3A
  • Coadministration with drugs highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events is contraindicated
  • Potential for other drugs to affect nirmatrelvir and ritonavir
  • Nirmatrelvir and ritonavir are CYP3A substrates; therefore, drugs that induce CYP3A may decrease nirmatrelvir and ritonavir plasma concentrations and reduce the therapeutic effect

Pregnancy and Lactation

• Nirmatrelvir
  • Human data are unavailable on the use of nirmatrelvir during pregnancy to evaluate for drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes
• Ritonavir
  • Observational studies on ritonavir use in pregnant females have not identified an increase in the risk of major birth defects
  • Studies with ritonavir are insufficient to identify a drug-associated risk of miscarriage
• Clinical considerations
  • There are maternal and fetal risks (eg, preeclampsia, eclampsia, preterm birth, premature rupture of membranes, venous thromboembolic disease, fetal death) associated with untreated COVID-19 in pregnancy
• Contraception
  • The use of ritonavir may reduce the efficacy of combined hormonal contraceptives
  • Advise patients using combined hormonal contraceptives to use an effective alternative contraceptive method or an additional barrier method of contraception
• Lactation
• Breastfeeding individuals with COVID-19 should follow practices according to clinical guidelines to avoid exposing the infant to COVID-19
• Nirmatrelvir
  • There are no available data on the presence of nirmatrelvir in human or animal milk, its effects on breastfed infants, or its effects on milk production
  • Transient decrease in body weight observed in nursing offspring of rats administered nirmatrelvir
• Ritonavir
  • Limited published data reports that ritonavir is present in human milk
  • There is no information on the effects of ritonavir on breastfed infants or its effects on milk production