What are the side effects of Paxlovid (nirmatrelvir and ritonavir)?

Side Effects of Paxlovid (Nirmatrelvir and Ritonavir)

The most common side effects of Paxlovid are altered sense of taste (dysgeusia, such as metallic or bitter taste) and diarrhea, with other potential side effects including headache, vomiting, abdominal pain, nausea, high blood pressure, and feeling generally unwell. 1

Common Side Effects

• Taste disturbances (dysgeusia):

  • Most frequently reported side effect
  • Often described as metallic or bitter taste
  • Typically resolves after completing treatment

• Gastrointestinal effects:

  • Diarrhea
  • Nausea
  • Vomiting
  • Abdominal pain

• Other common side effects:

  • Headache
  • High blood pressure
  • Malaise (feeling generally unwell)

Serious Side Effects

Allergic Reactions

• Severe allergic reactions (anaphylaxis) can occur
• Stop taking Paxlovid and seek immediate medical help if experiencing:
  • Skin rash, hives, blisters, or peeling skin
  • Painful sores or ulcers in mouth, nose, throat, or genital area
  • Swelling of mouth, lips, tongue, or face
  • Trouble swallowing or breathing
  • Throat tightness
  • Hoarseness 1

Liver Problems

• Monitor for signs of liver issues:
  • Loss of appetite
  • Yellowing of skin and eyes (jaundice)
  • Dark-colored urine
  • Pale colored stools
  • Itchy skin
  • Abdominal pain 1

Neurological Side Effects

Paxlovid has been associated with a higher rate of neurological adverse events compared to other COVID-19 medications, with particular attention needed for:

• Dysgeusia (altered taste)
• Ageusia (loss of taste)
• Headache
• Anosmia (loss of smell) 2

Drug-Drug Interactions

The ritonavir component of Paxlovid is a strong CYP3A inhibitor that can significantly increase serum levels of many medications, leading to potential adverse effects:

• High-risk interactions with medications metabolized through CYP3A4 pathway (approximately 60% of available medications) 3, 4

• Potential for serious interactions with:

  • Anticoagulants (warfarin, rivaroxaban)
  • Calcium channel blockers (nifedipine, manidipine, verapamil)
  • Statins (atorvastatin)
  • Immunosuppressants (tacrolimus)
  • Antiarrhythmics (amiodarone)
  • Antipsychotics (clozapine, quetiapine)
  • Ranolazine 5

• Management of drug interactions:

  • Review all patient medications before prescribing
  • Use the Liverpool COVID-19 Drug Interaction Tool to check potential interactions
  • Consider pausing interacting medications during Paxlovid treatment when possible 6, 3

Special Populations

Renal Impairment

• Dose adjustments required for patients with kidney disease:
  • Moderate renal impairment (eGFR ≥30 to <60 mL/min): 150 mg nirmatrelvir with 100 mg ritonavir, twice daily for 5 days
  • Severe renal impairment (eGFR <30 mL/min): 300 mg nirmatrelvir with 100 mg ritonavir on Day 1, followed by 150 mg nirmatrelvir with 100 mg ritonavir once daily on Days 2-5 1

Pregnancy and Breastfeeding

• Paxlovid represents an option for pregnant people with COVID-19
• No reports of serious adverse reactions in pregnant or breastfeeding individuals or their children in WHO Vigibase
• Breastfeeding is not contraindicated during Paxlovid treatment 7, 6

Clinical Pearls and Pitfalls

• Timing matters: Paxlovid must be initiated within 5 days of symptom onset for maximum efficacy 6

• Complete the full course: Do not stop taking Paxlovid without consulting a healthcare provider, even if symptoms improve 1

• Missed doses: If a dose is missed within 8 hours of the usual time, take it as soon as remembered. If more than 8 hours have passed, skip the missed dose and take the next dose at the regular time. Never take a double dose 1

• Drug interaction screening: Failure to screen for drug interactions can lead to adverse events. Always review all medications before prescribing Paxlovid 6

• Monitor female patients: Special attention should be paid to female patients taking Paxlovid within the first 30 days, monitoring for neurological side effects 2