COVID-19 Antiviral Side Effects: What to Expect and When to Call Your Doctor

If you've been prescribed Paxlovid or another COVID-19 antiviral, you probably have questions about what side effects to expect. Most people tolerate these medications well — and the benefits of preventing hospitalization far outweigh the side effects for high-risk patients. Here's what you need to know before you start treatment.

Paxlovid Side Effects: What's Most Common

Paxlovid (nirmatrelvir/ritonavir) is the most commonly prescribed COVID-19 antiviral, and its side effects are generally mild and manageable. The most frequently reported include:

• Dysgeusia (altered or metallic taste): The most commonly reported side effect. Food and drinks may taste metallic, bitter, or different than usual. This typically resolves after completing the 5-day course.
• Diarrhea: A common gastrointestinal side effect. Stay well-hydrated if this occurs. Mild diarrhea is not a reason to stop taking the medication.
• Elevated blood pressure (hypertension): Ritonavir can cause blood pressure to rise in some patients. If you already have hypertension, your provider may want to monitor you.
• Myalgia (muscle aches): Muscle discomfort during the treatment course. Often difficult to distinguish from COVID-19 symptoms themselves.
• Nausea and abdominal discomfort: Taking Paxlovid with food can help reduce nausea. Swallow tablets whole — do not crush or chew.

The Most Talked-About Side Effect: Paxlovid Rebound

"Paxlovid rebound" refers to a recurrence of COVID-19 symptoms or a return to a positive test after completing treatment. This has received significant media attention, but here's what the data actually show:

• COVID-19 rebound occurs in a subset of patients — both those who take Paxlovid AND those who took placebo in clinical trials
• The FDA has stated there is not a clear association between Paxlovid treatment and COVID-19 rebound — it appears to be a natural feature of the illness for some people
• The CDC says rebound is generally mild and does not require additional antiviral treatment in most cases
• Rebound is not a reason to avoid Paxlovid — the benefits of reducing hospitalization and death far outweigh this relatively minor risk

If you experience rebound, stay home, rest, and contact your provider. Resume isolation precautions if you test positive again.

Serious Side Effects: When to Call Your Doctor Immediately

While rare, serious side effects can occur. Seek medical attention immediately if you experience:

• Allergic reaction: Hives, difficulty breathing or swallowing, large swelling of the face, lips, tongue, or throat (angioedema). Stop Paxlovid and call 911 or go to the ER.
• Severe skin reaction: Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) are rare but serious rashes. Any rapidly spreading blistering rash requires immediate medical evaluation.
• Signs of liver problems: Ritonavir can cause hepatic transaminase elevations. Call your doctor if you develop yellowing of skin or eyes (jaundice), dark urine, or severe upper-right abdominal pain.
• Significant drug interaction symptoms: If you develop unusual symptoms after starting Paxlovid while on other medications — such as irregular heartbeat, extreme muscle pain (myopathy), or confusion — contact your provider immediately. This may indicate a drug interaction.

The Most Important Warning: Drug Interactions

Paxlovid's boxed warning — the most serious FDA warning — is about drug interactions. Ritonavir is a powerful CYP3A4 inhibitor that can dramatically increase blood levels of other medications. Some of the most dangerous interactions:

• Calcineurin inhibitors (tacrolimus, cyclosporine) — blood levels can spike dramatically; can cause kidney damage or toxicity
• Calcium channel blockers — blood levels increase; monitor for low blood pressure or dizziness
• Certain antiarrhythmics (amiodarone, ranolazine) — contraindicated due to risk of serious cardiac arrhythmias
• Certain statins (lovastatin, simvastatin) — contraindicated; can cause severe muscle breakdown (rhabdomyolysis)

Always give your provider a complete medication list — including over-the-counter medications, herbal supplements, and vitamins — before starting Paxlovid.

Side Effects of Remdesivir (Veklury)

Remdesivir, given as an IV infusion, has its own side effect profile. Common effects during infusion include nausea and decreased heart rate (bradycardia). Liver enzyme elevations have been reported and may be monitored. Unlike Paxlovid, Remdesivir does not have the same extensive drug interaction profile, though it should still be used with caution in patients with severe liver impairment.

Side Effects Are Manageable — Don't Let Fear Prevent Treatment

For high-risk patients, the risk of severe COVID-19 — hospitalization, ICU admission, death — far outweighs the risk of Paxlovid's manageable side effects. The metallic taste goes away. Diarrhea resolves. But avoiding antiviral treatment in a high-risk patient can have irreversible consequences. If you're concerned about interactions, read our detailed guide to COVID-19 antiviral drug interactions and discuss with your provider.