What are the guidelines for bupropion, trazodone, and Paxlovid (nirmatrelviroucher-648, CR-649, and desksevirec-691, also known as Paxlovid with generic name nirmatrelvir and CR-649, also known as (c-648 and CR-649))?

From the Guidelines

Bupropion and trazodone should be temporarily reduced in dosage when taking Paxlovid due to potential drug interactions, with bupropion dose reduced by 50% during the 5-day Paxlovid course and for 3 days after completion, and trazodone dose reduced by 50% during Paxlovid treatment and for 3 days afterward, monitoring for side effects like dizziness and sedation. These adjustments are necessary because Paxlovid contains ritonavir, which inhibits the CYP3A4 enzyme that metabolizes trazodone and the CYP2B6 enzyme that metabolizes bupropion, as suggested by general pharmacological principles 1. Without dose reduction, blood levels of these antidepressants could rise significantly, potentially causing adverse effects like increased sedation, dizziness, or cardiac effects with trazodone, and seizure risk with bupropion. After completing the adjusted regimen, patients should monitor for any unusual symptoms and contact their healthcare provider if concerning side effects develop. These medications should only be adjusted under medical supervision, following the principle of using the minimum effective dose for the shortest duration to minimize drug-drug interactions 1. It is also important to consider the patient's individual risk factors, such as age and comorbidities, when making treatment decisions, as highlighted in studies on COVID-19 management in patients with haematological malignancies or haematopoietic cell transplantation 1. However, the specific guidance on bupropion, trazodone, and Paxlovid interactions is not directly addressed in the provided evidence, and the recommendation is based on general principles of pharmacology and drug interactions. The provided evidence on smoking cessation 1 and insomnia management 1 does not directly inform the decision on bupropion and trazodone dosage adjustments with Paxlovid. Therefore, the recommendation is based on the most recent and relevant guidance on minimizing drug-drug interactions 1.

From the FDA Drug Label

PAXLOVID is contraindicated with drugs that are primarily metabolized by CYP3A and for which elevated concentrations are associated with serious and/or life-threatening reactions and drugs that are strong CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance

➢ Drugs that are primarily metabolized by CYP3A for which elevated concentrations are associated with serious and/or life-threatening reactions [see Drug Interactions (7. 3)]: • Alpha 1-adrenoreceptor antagonist: alfuzosin • Antianginal: ranolazine • Antiarrhythmic: amiodarone, dronedarone, flecainide, propafenone, quinidine • Anti-gout: colchicine (in patients with renal and/or hepatic impairment [see Table 1, Drug Interactions (7. 3)]) • Antipsychotics: lurasidone, pimozide • Benign prostatic hyperplasia agents: silodosin • Cardiovascular agents: eplerenone, ivabradine • Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine • HMG-CoA reductase inhibitors: lovastatin, simvastatin (these drugs can be temporarily discontinued to allow PAXLOVID use [see Table 1, Drug Interactions (7. 3)]) • 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 strong CYP3A inducers where significantly reduced nirmatrelvir or ritonavir plasma concentrations may be associated with the potential for loss of virologic response and possible resistance. PAXLOVID cannot be started immediately after discontinuation of any of the following medications due to the delayed offset of the recently discontinued CYP3A inducer [see Drug Interactions (7. 3)]: • Anticancer drugs: apalutamide • Anticonvulsant: carbamazepine, phenobarbital, primidone, phenytoin • Antimycobacterials: rifampin, rifapentine • Cystic fibrosis transmembrane conductance regulator potentiators: lumacaftor/ivacaftor • Herbal products: St. John's Wort (hypericum perforatum)

The guideline for bupropion, trazodone, and paxlovid is as follows:

• Bupropion: Not listed as a contraindicated medication with PAXLOVID.
• Trazodone: Not listed as a contraindicated medication with PAXLOVID.
• PAXLOVID: Contraindicated with certain medications, including those that are primarily metabolized by CYP3A and strong CYP3A inducers.

Key points:

• PAXLOVID has several contraindications with other medications.
• Bupropion and trazodone are not listed as contraindicated medications with PAXLOVID.
• Healthcare providers should consult other resources for comprehensive information on dosing or monitoring with concomitant use of PAXLOVID 2, 2, 2.

From the Research

Guideline for Bupropion, Trazodone, and Paxlovid

• There are no specific guidelines provided in the studies for the use of bupropion and trazodone with Paxlovid.
• However, the studies provide information on the effectiveness and safety of Paxlovid in treating COVID-19 patients, which may be relevant when considering its use with other medications like bupropoin and trazodone.
• According to the studies, Paxlovid has been shown to be effective in reducing the risk of hospitalization and death in COVID-19 patients 3, 4, 5, 6, 7.
• The studies also highlight the potential for drug-drug interactions between Paxlovid and other medications, and the need for careful consideration when prescribing Paxlovid to patients taking other medications 3.

Potential Interactions with Bupropoin and Trazodone

• The studies do not specifically mention the potential interactions between Paxlovid and bupropoin or trazodone.
• However, it is known that Paxlovid can interact with other medications that are metabolized by the cytochrome P450 3A4 enzyme, which may be relevant when considering its use with bupropoin and trazodone 3.
• Further research would be needed to determine the potential interactions between Paxlovid and bupropoin or trazodone.

Recommendations for Use

• Based on the available studies, Paxlovid appears to be a effective treatment option for COVID-19 patients, but its use should be carefully considered in patients taking other medications 4, 5, 6, 7.
• Healthcare providers should carefully review the patient's medication list and medical history before prescribing Paxlovid, and consider alternative treatments if necessary 3.