pemigatinib

Action and Spectrum

Actions and Spectrum: 

pemigatinib is a medication used to treat certain types of cancer, specifically locally advanced or metastatic cholangiocarcinoma (bile duct cancer). It generally belongs to a class of drugs called fibroblast growth factor receptor (FGFR) inhibitors. Here’s a brief overview of the action and spectrum of pemigatinib: 

• Action: pemigatinib works by inhibiting the activity of certain FGFRs, specifically FGFR1, FGFR2, and FGFR3. These receptors are proteins that play a role in cell growth, division, and angiogenesis (formation of new blood vessels). By blocking these receptors, pemigatinib helps to slow down/prevent the growth of cancer cells. 
• Spectrum: pemigatinib primarily treats cholangiocarcinoma, cancer originating in the bile ducts. It is indicated for patients with locally advanced or metastatic cholangiocarcinoma with a specific genetic alteration known as FGFR2 fusion or rearrangement. This genetic alteration leads to abnormal activation of the FGFR pathway, making the cancer cells more dependent on FGFR signaling for growth. 

It’s important to note that pemigatinib is prescribed by healthcare professionals. Its use should be guided by a comprehensive understanding of the patient’s condition, medical history, and genetic profile. The dosing, administration, and potential side effects of pemigatinib may vary depending on individual circumstances.

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Cholangiocarcinoma 

Enhanced creatinine (41%) 

Enhanced AST or ALT (43%) 

Dry eye (35%) 

Dry mouth (34%) 

Hypophosphatemia (23%) 

Enhanced calcium (43%) 

Enhanced urate (30%) 

Decreased lymphocytes (36%) 

Decreased albumin (34%) 

Alopecia (49%) 

Diarrhea (47%) 

Enhanced alkaline phosphatase (41%) 

Abdominal pain (23%) 

Peripheral edema (18%) 

Increased potassium (12%) 

Dry skin (20%) 

Decreased glucose (11%) 

Enhanced glucose (36%) 

Enhanced bilirubin (26%) 

Nail toxicity (43%) 

Pain in extremities (19%) 

Stomatitis (35%) 

Enhanced leukocytes (27%) 

Weight loss (16%) 

Vomiting (27%) 

Dysgeusia (40%) 

Constipation (35%) 

Decreased sodium (39%) 

Nausea (40%) 

Decreased hemoglobin (43%) 

Headache (16%) 

Hyperphosphatemia (60%) 

Decreased calcium (17%) 

Enhanced phosphate (94%) 

Fatigue (42%) 

Decreased platelets (28%) 

Back pain (20%) 

Arthralgia (25%) 

Decreased appetite (33%) 

Urinary tract infection (16%) 

Palmoplantar erythrodysesthesia syndrome (15%) 

Decreased potassium (26%) 

Dehydration (15%) 

Nausea (40%) 

1-10% 

Cholangiocarcinoma 

Increased bilirubin (6%) 

Increased potassium (2.1%) 

Palmoplantar erythrodysesthesia syndrome (4.1%) 

Increased calcium (4.1%) 

Diminished leukocytes (1.4%) 

Diminished calcium (2.7%) 

Increased AST (6%) 

Increased creatinine (1.4%) 

Decreased platelets (3.4%) 

Weight loss (2.1%) 

Increased ALT (4.1%) 

Diminished lymphocytes (8%) 

Stomatitis (5%) 

Increased urate (10%) 

Arthralgia (6%) 

Diminished hemoglobin (6%) 

Nail toxicity (2.1%) 

Back pain (2.7%) 

Diminished glucose (1.4%) 

Fatigue (4.8%) 

Urinary tract infection (2.7%) 

Abdominal pain (4.8%) 

Diarrhea (2.7%) 

Vomiting (1.4%) 

Pain in extremities (2.1%) 

Diminished potassium (5%) 

Dehydration (3.4%) 

Diminished appetite (1.4%) 

MLNs 

Palmoplantar erythrodysesthesia (9%) 

Increased alkaline phosphate (9%) 

Dry eye (6%) 

Increased glucose (3%) 

Diarrhea (2.9%) 

Abdominal pain (2.9%) 

Constipation (2.9%) 

Vision blurred (2.9%) 

Trichiasis (2.9%) 

Pyrexia (2.9%) 

Decreased calcium (2.9%) 

Increased calcium (2.9%) 

Decreased potassium (2.9%) 

Increased phosphate (2.9%) 

Decreased hemoglobin (9%) 

Decreased sodium (9%) 

Increased AST (9%) 

Rash (6%) 

Decreased appetite (6%) 

Hyperphosphatemia (2.9%) 

Fatigue (9%) 

Dizziness (9%) 

<1% 

Cholangiocarcinoma 

Increased glucose (0.7%) 

Peripheral edema (0.7%) 

Increased leukocytes (0.7%) 

Dry skin (0.7%) 

Dry eye (0.7%) 

Constipation (0.7%) 

Black Box Warning

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

pemigatinib is contraindicated in individuals with a known hypersensitivity to the drug or its components. It should not be used in pregnant condition or breastfeeding patients, as it may cause harm to the developing fetus or newborn. 

Additionally, pemigatinib may interact with certain medications, including potent CYP3A4 inhibitors, inducers, and medications that prolong the QT interval. Therefore, disclosing all current medications, supplements, and herbal products to a healthcare professional is vital before starting pemigatinib. 

Patients with severe renal impairment should also use pemigatinib with caution, as there is limited data on the safety and also the efficacy of the drug in this population. 

As with any medication, pemigatinib should be carefully considered and individualized based on the patient’s medical history, current medications, and overall health status. It is typically recommended to meet with a physician for personalized information and guidance regarding the contraindications and precautions associated with pemigatinib. 

Caution 

Here are some general cautions that may apply to pemigatinib: 

• Hepatic Impairment: pemigatinib should be used cautiously in patients with pre-existing liver conditions or impaired liver function. Close monitoring of liver function tests is advisable during treatment. 
• Cardiac Effects: pemigatinib may affect the QT interval, representing the time it takes for the heart to repolarize between beats. It is crucial to use pemigatinib cautiously in patients with a prior history of QT prolongation, electrolyte imbalances, or those taking medications that can prolong the QT interval. Regular monitoring of electrocardiograms (ECGs) may be recommended. 
• Eye Disorders: Some patients receiving pemigatinib may experience eye disorders such as dry eye, eye pain, blurred vision, or increased tearing. If any of these symptoms occur, informing the healthcare provider promptly is essential. 
• Gastrointestinal Effects: pemigatinib can cause gastrointestinal adverse effects, including diarrhea, nausea, vomiting, and abdominal pain. Adequate management of these symptoms, including supportive medications, hydration, and dietary adjustments, may be necessary. 
• Wound Healing: pemigatinib may affect wound healing. Before surgery, it’s crucial to inform the healthcare provider about using pemigatinib to assess the need for temporary discontinuation before and after surgical procedures. 

These general cautions may apply to pemigatinib, but it’s essential to consult the most recent prescribing information and discuss specific concerns with a healthcare professional. They can provide the most accurate guidance based on individual patient factors and the latest available information. 

Pregnancy / Lactation

Pregnancy consideration:  

US FDA pregnancy category: Not assigned 

Lactation:   

Excreted into human milk is Not known. 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies do not show risk to the fetus in the first/later trimester.        
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women        
• 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 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: 

pemigatinib selectively inhibits certain FGFR enzymes, particularly FGFR1, FGFR2, and FGFR3. By binding to the ATP-binding pocket of these receptors, pemigatinib prevents the activation of downstream signaling pathways involved in cell growth, differentiation, and angiogenesis. 

Pharmacodynamics: 

Mechanism of action: pemigatinib belongs to the class of orally bioavailable inhibitors targeting FGFR types 1, 2, and 3 (FGFR1/2/3). By inhibiting the phosphorylation and signaling of FGFR 1/2/3, pemigatinib effectively reduces cell viability in cancer cell lines that have to activate FGFR amplifications and fusions. 

Pharmacokinetics: 

Absorption 

pemigatinib is administered orally in the form of tablets. After the oral administration, it is rapidly absorbed from the gastrointestinal tract. The bioavailability of pemigatinib is increased when taken with food, although it can be taken with or without food. 

Distribution 

pemigatinib has a moderate volume of distribution. It is extensively bound to plasma proteins, primarily to albumin. 

Metabolism 

pemigatinib undergoes extensive hepatic metabolism. It is primarily metabolized by cytochrome P450 enzymes, mainly CYP3A4 and, to a lesser extent, by CYP2C9. The primary metabolites formed are M2 and M5, less active than the parent compound. 

Elimination and Excretion 

The primary route of elimination of pemigatinib is through feces, accounting for approximately 67% of the administered dose. Renal excretion plays a lesser role, accounting for about 22% of the dose. The elimination half-life of pemigatinib is approximately 36 hours. 

Adminstartion

Administration: 

Oral administration 

pemigatinib is available as oral tablets and should be taken precisely as a healthcare professional prescribes. Here are some general guidelines for the administration of pemigatinib: 

• Dosage: The dosage of pemigatinib will be determined by the prescribing healthcare professional based on factors such as the specific indication, patient characteristics, and overall treatment plan. It’s essential to consult a healthcare provider before following the prescribed dosage and only adjust or modify it. 
• Timing: pemigatinib is usually taken once daily, with or without food. The specific timing of administration may vary depending on the individual’s treatment plan, so it’s essential to follow the healthcare provider’s instructions. 
• Swallowing: The pemigatinib tablets should be swallowed whole with water and not crushed, chewed, or broken before consumption. 
• Missed Dose: If a dose is missed, taking it as soon as possible is generally recommended. However, if the next scheduled dose is missed, it should be skipped and the following dose should be taken at the appropriate time. It is important to avoid taking a double dose of the medication to compensate for the missed dose.
• Interactions: pemigatinib may interact with certain medications, so it’s essential to inform the healthcare provider about all current medications, including prescription drugs, over-the-counter medications, supplements, and herbal products. This will help ensure that potential drug interactions are identified and managed appropriately. 

It’s important to note that the administration instructions for pemigatinib may vary depending on individual circumstances and treatment protocols. Always follow the instruction provided by the healthcare professional prescribing pemigatinib and consult them or a pharmacist if there are any concerns/queries regarding administering the medication. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: pemigatinib 

Pronounced: [ PEM-i-GA-ti-nib ] 

Why do we use pemigatinib? 

pemigatinib is primarily used to treat a specific type of cancer called locally advanced or metastatic cholangiocarcinoma (bile duct cancer). It is specifically indicated for patients with cholangiocarcinoma with a specific genetic alteration known as FGFR2 fusion or rearrangement. The FGFR2 alteration leads to abnormal activation of the fibroblast growth factor receptor (FGFR) pathway, which plays key role in cell growth and division. 

pemigatinib is used when the cholangiocarcinoma is unresectable or has spread to other body parts (metastatic). It is for patients who have prior received at least one line of chemotherapy. 

A healthcare professional determines the specific use of pemigatinib based on various factors, including the patient’s medical history, genetic profile, stage of cancer, and overall treatment plan. The decision to use pemigatinib should be made in consultation with a physician who can assess the patient’s situation and recommend the most appropriate treatment options.