Paxlovid Drug Interactions List PDF Free Download

Paxlovid Drug Interactions List PDF Download Info

The Drug Paxlovid (Nirmatrelvir/ritonavir) Is A Cyp3a Inhibitor, And Such An Agent May Cause An Increase In Plasma Concentrations Of Drugs Almost Exclusively Metabolized Via Cyp3a. Drugs Exhibiting Extensive First Pass Metabolism And Larger Extent Of Cyp3a Metabolism Are Particularly At Risk For Clinically Relevant Increases In Exposure During The Concomitant Administration With Nirmatrelvir/ritonavir.

Paxlovid Drug Interactions List PDF Free Download

Thus, The Co-administration Of Nirmatrelvir/ritonavir With Drugs That Are Cleared To Almost A Completely Extent By Cyp3a And For Which Exposure Is Associated With Serious Or Life-threatening Events Is Contraindicated (See The Table 1, Section 4.3 Contraindications).

In Vitro And At Therapeutically Relevant Concentrations, Nimatrelvir Demonstrated No Measurable Reversible Inhibition Of Cyp2d6, Cyp2c9, Cyp2c19, Cyp2c8, And Cyp1a2 Or Ugt1a1, Ugt1a4, Ugta6, Ugt1a9, Ugt2b7, And Ugtb15. It Is Not Likely That Nirmatrelvir Would Activate The Cyp1a2, Cyp2c19, Cyp2b6, Cyp2c8, Or Cyp2c9 Enzymes.

In Vitro, Nirmatrelvir Was Shown To Weakly Inhibit Bcrp, Mate2k, Oat1, Oat3, Oatp1b3, Oct1, And Oct2. In Vitro, At Clinically Relevant Concentrations, Nirmatrelvir Is Known To Inhibit Mdr1 (P-gp), Mate1, And Oatp1b1.

Ritonavir May Be A Strong Oxidation Inhibitor In The Following Ordered Order Because Of Its Affinity For A Number Of Cyp Isoforms: Cyp2a6 >> Cyp1a2, Cyp2e1, Cyp2d6 > Cyp2c9, Cyp2c19.

Ritonavir May Also Be A P-gp Inhibitor Due To A High Affinity For This Product. Ritonavir May Induce Glucuronidation And Oxidation Through Cyp1a2, Cyp2c8, Cyp2c9, And Cyp2c19, With An Enhancement Of The Drug Metabolism Through These Pathways.

This Might Result In A Reduction In Systemic Exposure To These Pharmaceuticals, Thereby Causing A Possible Diminishment Or Shortening Of Their Therapeutic Effect.

This Practice Should Only Be Considered When The Benefits Of Co-administration Of Other Cyp3a4 Substrates Outweigh The Potential Risks Of Potential Drug Interactions That Could Be Harmful (See Table 2). Since Ritonavir And Nirmatrelvir Are Cyp3a Substrates, Inducers Of Cyp3a May Reduce Ritonavir And Nirmatrelvir Plasma Concentrations And Diminish The Therapeutic Effect Of Paxlovid.

Listed Below Are The Drug-drug Interactions Related To Ritonavir In Table 1 (See To Section 4.3 Contraindications) And 2. They Need To Apply For Paxlovid As Well, For Just A Piece Of Mind.

The Drugs In Tables 1 (Section 4.3 Contraindications) And 2 Are Only Indicative; There Is No Utility In Tabulating Every Medication That Might Interact With Nirmatrelvir/ritonavir. If A Clinician Wishes To Learn More, They Can Refer To The Appropriate Sources.

Proof Of Safety For Paxlovid Comes From Study C4671005 (Epic-hr), A Phase 2/3 Randomised, Placebo-controlled Study In Non-hospitalised Adult Patients Who Are At Increased Risk For Severe Covid-19 Disease And Laboratory Confirmed Sars-cov-2 Infection (See Section 5.1 Pharmacodynamic Characteristics, Clinical Studies). Symptomatic Adult Patients Aged ≥18 Years Were Treated With At Least One Dose Of Either Paxlovid (N = 1,109) Or Placebo (N = 1,115).

The Adverse Events Were Defined As All Those Occurring From The Time Of The Study’s Drug Phase And Until Day 34 Post-commencement Of The Study’s Therapy. The Participant Had To Take, Orally Twice Daily For Five Days, Either Placebo Or Paxlovid (300 Mg Nirmatrelvir With 100 Mg Ritonavir).

Table 3. Adverse Events Of All Grades, Regardless Of Causality For The Group Treated With Paxlovid. Dysgeusia, Diarrhea, Headache, And Vomiting Were The Most Common Side Effects In The 34 Days Following Treatment With Paxlovid. See Table 4.

A Higher Proportion Of Patients In The Paxlovid Group Discontinued Treatment Because Of An Adverse Event Than In The Placebo Group. 18 (1.6%) Patients In The Paxlovid And Placebo Group Experienced A Serious Adverse Event.

Data From Epic-hr: Phase 2/3 Randomized, Double-blind, Placebo-controlled Study In Outpatient, Symptomatic Adults Who Have Confirmed Sars-cov-2 Infection Serves As Efficacy Data For Paxlovid.

This Comprised Individuals Who Satisfied The Inclusion Criteria To Participate In The Study, Either Being 60 Years Of Age Or Older, Independent Of Comorbidities, Or 18 Years Of Age And Above With At Least One Of The Following Risk Factors For The Progression To Severe Disease:

Diabetes, Overweight (Bmi > 25), Chronic Kidney Disease, Chronic Lung Disease (Including Asthma), Chronic Kidney Disease, Current Smoking, Immunosuppressive Disease Or Immunosuppressive Treatment, Cardiovascular Disease, Hypertension, Diabetes, Sickle Cell Disease, And Neurodevelopmental Disorders.

Individuals With Documented Proof Of Covid-19 Infection Or Vaccination Are Excluded For This Trial. Enrolled Participants Were Those Whose Symptoms Related To Covid-19 Developed In 5 Days Or Less. Percentage Of Hospitalization Or Death Due To Any Cause Associated With Covid-19 By Day 28 Is Considered As The Primary Endpoint Of Effectiveness.

All Treated Patients In Whom Symptoms Had Begun ≤ 3 Days At Baseline Were Included In The Mitt Analysis Set In Whom Covid-19 Therapeutic Mab Treatment Was Neither Administered Nor Expected.

In All The Treated Patients In Whom Symptoms Began ≤ 5 Days And At Baseline Did Not Receive Nor Were Expected To Receive Covid-19 Therapeutic Mab Treatment, The Mitt1 Analysis Set Was Used And The Analysis Was Done. All Treated Subjects In The Mitt2 Analysis Set Had Onset Of Symptoms ≤ 5 Days.

Total Participants Randomized To Either Placebo Or Paxlovid: 2,246. Baseline Population’s Mean Age Was 46 Years With 51% Men, 72% White People, 5% Black People, 14% Asian People, And 45% Hispanic Or Latino.

47% Of Participants Were Serologically Negative At Baseline, And 66% Of Participants Had Symptoms That Began Within Three Days Of Initiation Of Study Drug. Baseline Viral Load Mean (Sd) Was 4.63 Log10 Copies/ml (2.87);

In 26% Of Participants, The Baseline Viral Load Was Higher Than 10^7 Units. At The Time Of Randomization, 6% Of The Subjects Were Receiving Or Would Likely Receive Therapeutic Monoclonal Antibody Covid-19 Therapy And Were Thus Excluded From The Mitt And Mitt1 Analyses.

The Demographic And Illness Characteristics At Baseline Were Similar Between Patients In The Paxlovid And Placebo Groups.

697 (62.2%) Participants In The Paxlovid Treatment Group, And 682 (60.6%) Participants In The Placebo Group, Were Included In The Mitt Analysis Set As Of Pcd Analysis.

In The Mitt Data Set, In The Context Of Patients Who Started Treatment Within Three Days Of Symptom Onset, The Rate Of A Covid-19-related Hospitalization Or Death From Any Cause Through Day 28 Was 5/697 (0.72%) In The Paxlovid Group And 44/682 (6.45%) In The Placebo Group.

Primary Outcome Events: In Comparison With Placebo, Relative Reduction In Primary Outcome Events Was 88.9%, Representing An Absolute Reduction Of 5.81% (95% Ci: -7.78% To -3.84; P<0.0001). Compared With Nine Deaths In The Group Receiving A Placebo, No Deaths Were Observed In The Group That Received Paxlovid.

Table 5 Shows The Primary Endpoint Results For The Mitt1 Analysis Population. The Relative Risk Difference Between Paxlovid And Placebo For The Main Outcome In The Mitt1 Study Population Is 88% (95% Ci: 75%, 94%).