pirtobrutinib

Action and Spectrum

Actions and Spectrum:

pirfenidone is a drug used to treat idiopathic pulmonary fibrosis (IPF), a lung disease characterized by the buildup of scar tissue in the lungs. It works by reducing inflammation and slowing down the progression of fibrosis. Pirfenidone is thought to interfere with the activity of certain chemical signals in cells that contribute to inflammation and scarring.

The exact mechanism of action of pirfenidone is not fully understood, but it is thought to work by modulating the activity of various signaling pathways involved in the regulation of cellular growth and survival. In particular, pirfenidone is thought to interfere with the activity of the transforming growth factor-beta (TGF-beta) pathway, which is a key player in the development and progression of IPF.

Drug Interaction

Adverse Reaction

Frequency Defined 

1-10% 

Headache (3%)

Sinus tachycardia (2%)

Bradycardia (3%)

QT prolonged (3%)

Tachycardia (5%)

Epistaxis (1%)

QRS prolonged (2%)

>10%

Hypertension (78%)

Black Box Warning

Black Box Warning

The FDA has issued a black box warning for the drug pirtobrutinib, indicating that the medication can cause serious and potentially life-threatening bleeding events. This warning applies to patients who take pirtobrutinib to treat mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL).

Contraindication / Caution

Contraindication/Caution:

• Pirtobrutinib is contraindicated in patients with known hypersensitivity to pirtobrutinib or any of its components.
• Caution should be exercised in patients with bleeding disorders, as pirtobrutinib may increase the risk of bleeding. Additionally, patients receiving pirtobrutinib should be monitored for the development of infections, and use of the drug should be discontinued if severe or life-threatening infections occur.
• Patients should be advised to avoid vaccination with live vaccines while receiving pirtobrutinib, as it may weaken the immune response to the vaccine.
• Inform healthcare providers of all current medications, including over-the-counter drugs and dietary supplements, as interactions with pirtobrutinib may occur.
• Finally, women who are pregnant or planning to become pregnant should inform their healthcare provider, as the safety of pirtobrutinib during pregnancy has not been established.

Pregnancy / Lactation

Pregnancy warnings:   

US FDA pregnancy category: N/A

Lactation:  

Excreted into human milk is known

Pregnancy Categories:        

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester.

Category B: There were lack of studies on pregnant women and no evidence of risk to the foetus in animal experiments.

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology: 

Pirtobrutinib is a selective, orally bioavailable, irreversible inhibitor of Bruton’s tyrosine kinase (BTK). It is used for the treatment of various hematologic malignancies, such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL).

Pharmacodynamics:  

Pirtobrutinib selectively targets BTK, an important signaling molecule that plays a crucial role in the activation of B cells and the regulation of immune response. By inhibiting BTK, pirtobrutinib blocks the activation of the B cell receptor (BCR) signaling pathway, which is frequently dysregulated in B-cell malignancies and leads to inhibition of B-cell proliferation and survival.

Pharmacokinetics:  

Absorption 

pirtobrutinib is rapidly and completely absorbed after oral administration, with peak plasma concentrations reached within 1-2 hours.

Distribution 

It is highly bound to plasma proteins, with a binding rate of 99.9%.

Metabolism 

pirtobrutinib is primarily metabolized by cytochrome P450 (CYP) 3A4, with lesser contributions from CYP2D6, CYP2C8, CYP2C9, and CYP3A5.

Elimination and Excretion 

pirtobrutinib and its metabolites are primarily excreted in the feces, with a small portion excreted in the urine.

Half-Life: The half-life of pirtobrutinib is approximately 11 hours.

Adminstartion

Administration: 

Oral administration

pirtobrutinib is typically administered orally, as a tablet, taken once daily. The specific dosing schedule and duration of treatment may vary depending on the individual patient’s condition and response to the medication.

It is important to take pirtobrutinib exactly as directed by a healthcare provider, and not to change the dose or frequency of the medication without medical advice. Patients should also avoid eating grapefruit or drinking grapefruit juice while taking pirtobrutinib, as this can increase the risk of side effects.

If a dose is missed, patients should take it as soon as possible, unless it is almost time for the next dose. In this case, patients should skip the missed dose and continue with their regular schedule.

Patient Information Leaflet

Patient information leaflet

Generic Name: pirtobrutinib

Why do we use pirtobrutinib?

pirtobrutinib is a medication used for the treatment of certain types of blood cancers and other blood disorders. Specifically, it is used to treat mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).