Medication Safety Considerations for COVID-19 Treatment Paxlovid

Pfizer’s Paxlovid (nirmatrelvir tablets and ritonavir tablets, co-packaged for oral use) received emergency use authorization (EUA) for the FDA on Dec. 22, 2021 for the treatment of mild-to-moderate COVID-19 in adults and children 12 years and older weighing at least 40 kilograms (88 pounds) with positive results of direct SARS-CoV-2 testing who are at high risk of progression to severe disease.

Pfizer has begun distributing Paxlovid, but it is available in limited supply. According to HHS, 64,970 courses had been distributed as of Jan. 7, 2022.

But the Institute for Safe Medication Practices (ISMP) has issued important safety concerns regarding Paxlovid and recommendations for physicians and pharmacists when prescribing and dispensing the medication.

According to the EUA, the recommended dose of Paxlovid for patients with normal renal function or mild renal impairment (estimated glomerular filtration rate (eGFR) > 60 to < 90 ml/min) is 300 milligrams of nirmatrelvir (two, 150 mg tablets) with 100 milligrams ritonavir (one 100 mg tablet). Additionally, all 3 tablets must be taken together orally twice daily for five days.

Patients with moderate renal impairment (eGFR > 30 to < 60 ml/min) are supposed to take smaller doses: 150 mg of nirmatrelvir (one tablet) with 100 mg ritonavir (one tablet) taken together twice daily for five days. And patients with severe renal impairment (eGFR < 30 ml/min) are supposed to avoid Paxlovid altogether.

It is important for pharmacists to remove one of the nirmatrelvir tablets for both the morning and evening doses from each blister card and cover the empty blisters with pre-printed moderate renal impairment dosing instructions on all five cards with manufacturer-supplied stickers prior to dispensing Paxlovid. Pharmacists are also supposed to educate patients with moderate renal impairment that the packaging was altered to reflect the dosing changes.

Pharmacies can contact C19therapies@amerisourcebergen.com to obtain additional stickers. Pharmacies should ensure that their staff are educated about these essential steps. Additionally, prescribers should ensure that the appropriate dosing is on all Paxlovid prescriptions for patients with moderate renal impairment. 

There are also drug interactions to be aware of with Paxlovid because it is an inhibitor of CYP3A, and it is critical for pharmacists to educate prescribers and patients about these since they can result in decreased Paxlovid efficacy or toxicity of the patient’s other therapies. Paxlovid treatment is contraindicated with the following medications:

• Alpha1-adrenoreceptor antagonist: alfuzosin
• Analgesics: pethidine, piroxicam
• Antianginal: ranolazine
• Antiarrhythmics: amiodarone, dronedarone, flecainide, propafenone, quinidine
• Anti-gout: colchicine
• Antipsychotics: lurasidone, pimozide, clozapine
• Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine
• Statins: lovastatin, simvastatin
• PDE5 inhibitor: sildenafil (Revatio) for pulmonary arterial hypertension
• Sedative/hypnotics: triazolam, oral midazolam
• Anticancer drugs: apalutamide
• Anticonvulsants: carbamazepine, phenobarbital, phenytoin
• Antimycobacterials: rifampin
• Herbal products: St. John’s Wort