Managing Bad, Bitter and Metallic TASTE from Paxlovid

The U.S. Food and Drug Administration has issued an EUA for the emergency use of the unapproved PAXLOVID which is combination of nirmatrelvir, a SARS-CoV-2 main protease (Mpro: also referred to as 3CLpro or nsp5 protease) inhibitor, and ritonavir, an HIV-1 protease inhibitor and CYP3A inhibitor, for the treatment of mild-to-moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive test of direct severe acute respiratory syndrome coronavirus 2

Administer orally with or without food within 5 days of COVID infection.

Dosage: 300 mg nirmatrelvir (two 150 mg tablets) with 100 mg ritonavir (one 100 mg tablet), with all three tablets taken together twice daily for 5 days

Dose reduction for moderate renal impairment (eGFR ≥30 to <60 mL/min): 150 mg nirmatrelvir (one 150 mg tablet) with 100 mg ritonavir (one 100 mg tablet), with both tablets taken together twice daily for 5 days

PAXLOVID is not recommended in patients with severe renal impairment (eGFR <30 mL/min) or severe hepatic impairment (Child-Pugh Class C)

CONTRAINDICATIONS:

Co-administration with drugs highly dependent on CYP3A for clearance and for which elevated concentrations are associated with serious and/or life-threatening reactions

Alpha1-adrenoreceptor antagonist: alfuzosin 

Analgesics: pethidine 

Antianginal: ranolazine 

Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone, quinidine 

Anti-gout: colchicine

Antipsychotics: lurasidone, pimozide, clozapine 

Benign prostatic hyperplasia 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), viagra

Sedative/hypnotics: triazolam, oral midazolam 

Serotonin receptor 1A agonist/serotonin receptor 2A antagonist: flibanserin 

Vasopressin receptor antagonists: tolvaptan

Co-administration with potent CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance

Anticancer drugs: apalutamide 

Anticonvulsant: carbamazepine, phenobarbital, primidone, phenytoin

Cystic fibrosis transmembrane conductance regulator potentiators: lumacaftor/ivacaftor 

Antimycobacterials: rifampin

Herbal products: St. John’s Wort (hypericum perforatum)

Cytochrome P450 3A (including 3A4) inhibitors and inducers

Strong inhibitors	Moderate inhibitors	Strong inducers	Moderate inducers
Atazanavir Ceritinib Clarithromycin Cobicistat and cobicistat-containing coformulations Darunavir Idelalisib Indinavir Itraconazole Ketoconazole Levoketoconazole Lonafarnib Lopinavir Mifepristone Nefazodone Nelfinavir Ombitasvir-paritaprevir-ritonavir Ombitasvir-paritaprevir-ritonavir plus dasabuvir Posaconazole Ritonavir and ritonavir-containing coformulations Saquinavir Telithromycin Tucatinib Voriconazole	Amiodarone* Aprepitant Berotralstat Cimetidine* Conivaptan Crizotinib Cyclosporine* Diltiazem Duvelisib Dronedarone Erythromycin Fedratinib Fluconazole Fosamprenavir Fosaprepitant* Fosnetupitant-palonosetron Grapefruit juice Imatinib Isavuconazole (isavuconazonium sulfate) Lefamulin Letermovir Netupitant Nilotinib Ribociclib Schisandra Verapamil	Apalutamide Carbamazepine Enzalutamide Fosphenytoin Lumacaftor Lumacaftor-ivacaftor Mitotane Phenobarbital Phenytoin Primidone Rifampin (rifampicin)	Bexarotene Bosentan Cenobamate Dabrafenib Dexamethasone¶ Dipyrone Efavirenz Elagolix, estradiol, and norethindrone therapy packΔ Eslicarbazepine Etravirine Lorlatinib Mitapivat Modafinil Nafcillin Pexidartinib Rifabutin Rifapentine Sotorasib St. John's wort

Adverse events (all grades regardless of causality) in the PAXLOVID group (≥1%) that occurred at a greater frequency (≥5 subject difference) than in the placebo group were dysgeusia (6% and <1%, respectively), diarrhea (3% and 2%), hypertension (1% and <1%), and myalgia (1% and <1%).

Paxlovid can cause dysgeusia, which is a change in the taste in your mouth. A bitter or metallic taste in the mouth shortly after taking their first set of pills has been reported.

Managing Dysguesia:

1. Take Cold material beforehand to numb taste buds (popsicle, ice cube).

2. Put the pill at the very back of patient's tongue and swallow with whole glass of water

3. Coat COVID positive patient's tongue (back area) with honey or maple syrup for 30 seconds before and  1-2 minutes after taking Paxlovid 

4. Take honey cough drops during the course of treatment and 

5. Use candy to MANAGE bitter taste

6. Keep taking Zinc 50 mg twice daily for 1 week after the infection

Main cause of dysgeusia is zinc deficiency. It has been reported that zinc is partly responsible for the repair and production of taste buds

Bitter taste usually decreases in one to two days after the course of treatment.

References:

https://www.fda.gov/media/155050/download