Dr. Ahmed Jaypirca (Pirtobrutinib) is a medication that is used to treat mantle cell lymphoma (MCL) that is relapsed or resistant to other treatments. It is also safe and effective to be used in children.
Brand Name: Jaypirca
Medical Name: Pirtobrutinib
Class: BTK (Bruton’s Tyrosine Kinase) Inhibitor
FDA-Approval Date: 27th January 2023
Primary Indication: Refractory or relapsed Mantle Cell Lymphoma
Jaypirca (Pirtobrutinib) FDA-Approved Indications:
JAYPIRCA is a Bruton’s Tyrosine Kinase Inhibitor (BTK-Inhibitor). It has been approved by the FDA for treating mantle cell lymphoma in patients who have not responded adequately to previous therapies, including a BTK inhibitor and at least two first-line of chemotherapeutic drugs.
It is indicated for the treatment of relapsed cases or refractory cases of mantle cell lymphoma.
Jaypirca (Pirtobrutinib) Dose Recommendation:
The usual recommended dose is 200 mg orally once a day. The treatment is continued until the toxic effects of the drugs are observed or the disease is noted to progress despite the treatment.
The tablets should be swallowed whole with water. Avoid cutting, crushing, or chewing them. The drug should be taken daily at the same time of the day without regard to meals or food.
If a person forgets to take the dose at the scheduled time, it should be taken immediately. However, if more than 12 hours have passed, skip the dose and wait for the next dose.
Dose modification due to side effects:
Adverse Reaction | Dosage Modification |
| First Occurrence | Interrupt JAYPIRCA until the adverse reaction is resolved or reduced to Grade 1 or baseline. Restart the dose at the usual recommended dose of 200 mg once daily. |
| Second Occurrence | Withhold the treatment until the side effects have resolved or improved to at least Grade 1. Restart the dose at half the usual recommended dose (100 mg once daily). |
| Third Occurrence | Stop the treatment until the side effects have resolved or improved to Grade 1. Restart the dose at a much lower dose i.e. 50 mg once daily. |
| Fourth Occurrence | Discontinue the treatment permanently. |
Lymphocytosis can occur; however, in asymptomatic patients, adjusting the dose is not recommended.
Dosage modifications for JAYPIRCA in specific situations:
Situation | Dosage Modification |
| Severe Renal Impairment (eGFR 15-29 mL/min) | Reduce the dose to 100 mg orally once daily if the current dose is 200 mg once daily, otherwise, reduce to 50 mg. Discontinue the treatment if the current dose is 50 mg once daily. |
| Mild to Moderate Renal Impairment (eGFR 30-89 mL/min) | No modification recommended |
| Concomitant use with Strong CYP3A Inhibitors | Avoid it if possible. If unavoidable, reduce the JAYPIRCA dose by 50 mg. Interrupt JAYPIRCA treatment if currently taking 50 mg once daily. Resume the previous dose after 5 half-lives of the CYP3A inhibitor. |
| Concomitant use with Strong or Moderate CYP3A Inducers | Avoid concomitant use with strong or moderate CYP3A inducers. However, if one can not avoid it, increase the dose to 300 mg. For current dosages of 50 mg or 100 mg once daily, increase by 50 mg. |
Jaypirca Dose form and strength:
Tablet | Appearance | Debossing |
| 50 mg | Blue, arc-triangle shaped | “Lilly 50” on one side, “6902” on the other |
| 100 mg | Blue, round | “Lilly 100” on one side, “7026” on the other |
Contraindications to Pirtobrutinib (Jaypirca):
No contraindication is given in the FDA prescribing information.
The warnings and precautions for JAYPIRCA are listed in the table below:
Safety Information | Recommendations |
| Infections | Consider prophylaxis in patients at increased risk. Monitor for the clinical features of infection and treat promptly with appropriate antibiotics. In severe infection, the treatment may be discontinued. |
| Hemorrhage | Consider the risk of bleeding and monitor (for bleeding) in patients on antithrombotic drugs. The treatment may be discontinued in severe cases and after major surgery. |
| Cytopenias | Monitor for cytopenias and adjust or discontinue the treatment if required. |
| Atrial Fibrillation/Flutter | Monitor for arrhythmias. Educate the patients to report palpitations and shortness of breath. In severe cases, the treatment may be discontinued. |
| Second Primary Malignancies | Advise patients to use sunscreens. Monitor for second primary malignancies. |
| Embryo-Fetal Toxicity | The drug is toxic to the fetus. Ensure effective contraception during the treatment and one week after the treatment. |
Side effects of Jaypirca (Pirtobrutinib):
Side Effects | Description |
Severe | |
| Infections | Fatal and serious infections and sepsis can occur in patients with febrile neutropenia |
| Hemorrhage | Fatal and serious bleeding including major bleeding episodes can occur. |
| Cytopenias | Grade 3 or 4 cytopenias |
| Atrial Fibrillation and Atrial Flutter | Atrial fibrillation and atrial flutter |
| Secondary Malignancies | Solid tumors and melanoma |
Common | |
| Infections | Grade 3 or higher infections especially pneumonia |
| Hemorrhage | Bleeding of any grade, excluding bruising and petechiae |
| Cytopenias | Neutropenia, anemia, thrombocytopenia |
| Atrial Fibrillation and Atrial Flutter | Atrial fibrillation or flutter |
Less Common | |
| Infections | Opportunistic infections |
| Hemorrhage | Major bleeding especially with the concomitant use of antithrombotic drugs |
| Cytopenias | Grade 4 neutropenia and thrombocytopenia |
| Embryo-Fetal Toxicity | Fetal harm |
Side effects experienced in clinical trials:
| Adverse Reactions (by System Organ Class) | Rate (%) |
| Neutropenia | 41 |
| Anemia | 37 |
| Thrombocytopenia | 27 |
| Tiredness | 27 |
| Skeletal pain | 26 |
| Lymphocytopenia | 24 |
| Bruising | 20 |
| Diarrhea | 20 |
Drug interactions:
| Drugs | Effect on JAYPIRCA | Recommendation |
| Strong CYP3A Inhibitors | Increases Jaypirca’s systemic exposure | Avoid concomitant use of strong CYP3A inhibitors. May reduce the dose of JAYPIRCA if the strong CYP3A4 inhibitor can not be avoided. |
| Strong or Moderate CYP3A Inducers | Decreases Jaypirca’s systemic exposure | Avoid concomitant use of strong or moderate CYP3A inducers. If moderate CYP3A inducers are unavoidable, increase the JAYPIRCA dosage |
| Effect of JAYPIRCA on Other Drugs | P-gp inhibitor, moderate CYP2C8 and BCRP inhibitor, and weak CYP2C19 and CYP3A inhibitor | Increases plasma concentrations of sensitive P-gp, CYP2C8, BCRP, CYP2C19, or CYP3A substrates |
| Risks Associated with Increased Concentrations of Substrates | This may increase the risk of adverse reactions | Follow recommendations for sensitive CYP2C8, CYP2C19, CYP3A, P-gp, or BCRP substrates provided in their approved product labeling |
Use of Jayprica in specific populations:
| Category | Description |
| Pediatric Use | Not studied in children. |
| Geriatric Use | Data is limited however, older people are at an increased risk of developing side effects. |
| Renal Impairment | No need to adjust the dose for mild and moderate renal impairment. In severe renal impairment, reduce the dose. |
| Hepatic Impairment | Dosage adjustment is not recommended in patients with liver disease of any severity. |
| Pregnancy | |
| Risk Summary | Jaypirca is toxic to the fetus. Pregnancy should be avoided using effective contraception during the treatment and for at least one week after the last dose. |
| Lactation | |
| Risk Summary | No information is available. Breastfeeding is not recommended during the treatment and at least for a week after the last dose. |
| Females and Males of Reproductive Potential | |
| Pregnancy Testing | Test for pregnancy in females of reproductive ages before initiating the treatment. |
| Contraception | Effective contraception is recommended during the treatment for at least one week after the last dose. |
Mechanism of Action (MOA) of Pirtobrutinib (Jaypirca):
Pirtobrutinib belongs to the class of medicines called Bruton’s tyrosine kinase (BTK) inhibitors.
BTK is an important signaling protein for the B-cell antigen receptor (BCR) and cytokine receptor pathways.
BTK is a signaling protein that activates pathways that are essential for B-cell functions such as proliferation, trafficking, chemotaxis, and adhesion.
Pirtobrutinib targets both the normal BTK and BTK with C481 mutations resulting in the inhibition of BTK kinase activation of B cells. Hence, it inhibits BTK-mediated functions of B-cells CD69 expression and proliferation.
Cardiac Electrophysiology:
No significant effect on the QTc interval.
Pharmacokinetics | Information |
| Dose Proportionality | Pirtobrutinib exposure (AUC) and Cmax increase proportionally |
| Steady State | 5 days |
| Absolute bioavailability | 85.5% (range 75.9% to 90.9%). |
| Peak plasma concentration | 2 hours |
| Effect of Food | A high-fat meal decreased the Cmax of Pirtobrutinib by 23% and delayed the Tmax by 1 hour. |
| Protein binding | 96%. |
| Elimination | 19 hours |
| Metabolism |
|
| Excretion |
|
Clinical studies:
| Aspect | Details |
| Study Name | BRUIN (NCT03740529) [Ref] |
| Participants | The study enrolled 120 patients with mantle cell lymphoma who had been previously treated with Bruton’s tyrosine kinase (BTK) inhibitors. Those with active CNS lymphoma, who had undergone allogeneic HSCT, or had received CAR) T-cell therapy within 60 days were excluded from the study. |
| Treatment | Enrolled patients were given JAYPIRCA orally at a dose of 200 mg once daily. |
| Outcome | Overall response rate (ORR) and duration of response (DOR) were evaluated based on 2014 Lugano criteria by an independent review committee (IRC) |
| Results | The median age of patients was 71 years (79% were male) ORR was 66.7% (80/120) with a complete response (CR) rate of 28.3% (34/120) and partial response (PR) rate of 38.3% (46/120); the median duration of response was 19.5 months. |
Conclusion: In patients with MCL who had previously been treated with a BTK inhibitor, JAYPIRCA demonstrated an ORR of 66.7% with a median duration of response of 19.5 months.
Patient counseling information:
Topic | Counseling Information |
| Patient Labeling | Patients should read the FDA handout. |
| Infections | Serious infections can occur during the treatment. Patients should report any signs of infection instantly |
| Bleeding | Bleeding can occur. During major surgeries, the treatment may be temporarily stopped. |
| Cytopenias | Frequent monitoring of blood counts is important to identify marrow toxicity earlier. |
| Atrial arrhythmia | Atrial fibrillation and flutter have been reported during the treatment. patients should be asked to report symptoms of shortness of breath and palpitations. |
| Second Primary Malignancies | There is a risk of skin cancer and other solid tumors. Patients should limit sun exposure and use sunscreens. Monitoring for solid tumors is also important. |
| Embryo-Fetal Toxicity | The drug is toxic to the fetus. Effective contraception should be used during the treatment and at least one week after the last dose. |
| Lactation | Breastfeeding is not recommended until one week after the last dose. |
| Administration | The drug should be taken daily at the scheduled time. Crushing the tablet, chewing, or cutting is not recommended. In addition, one should not make up for a missed dose if more than 12 hours have passed. |
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