mitomycin pyelocalyceal

Action and Spectrum

Actions and Spectrum: 

• mitomycin exerts its anticancer effects through its unique mechanism of action. It is classified as an alkylating agent, which means it works by damaging the DNA of cancer cells. The drug undergoes biotransformation in the body and produces reactive intermediates that covalently bind to DNA, causing cross-linking between DNA strands. This cross-linking interferes with DNA replication and transcription, leading to cell cycle arrest and death. 
• mitomycin has a broad spectrum of activity against various tumor types. When used in the pyelocalyceal region, it is primarily employed for treating superficial urothelial carcinoma of the kidney. Superficial urothelial carcinoma refers to cancer confined to the kidney’s inner lining (renal pelvis and calyces) without invading deeper into the kidney tissue. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% (All grades) 

Flank pain (39%) 

Hematuria (32%) 

Nausea (24%) 

Abdominal pain (23%) 

Dysuria (21%) 

Vomiting (20%) 

Ureter stenosis (44%) 

Urinary tract infection (34%) 

Renal dysfunction (25%) 

Fatigue (24%) 

Laboratory anomalies worsen from baseline 

eGFR (37%) 

Hypoalbuminemia (30%) 

Thrombocytopenia (21%) 

Anemia (37%) 

Increased creatinine (32%) 

Lymphopenia (21%) 

Hypocalcemia (17%) 

>10%(Grade 3 and 4) 

Hyperuricemia (16%) 

1-10% All Grades H3 

Urinary tract obstruction (6%) 

Obstructive uropathy (1.4% 

Ureteropelvic obstruction (6%) 

Ureteric obstruction (2.8%) 

1-10% (Grades 3-4) 

Hydronephrosis (6%) 

Vomiting (4.2%) 

Hematuria (2.8%) 

Ureteropelvic obstruction (1.4%) 

Urinary tract infection (4.2%) 

Flank pain (2.8%) 

Renal dysfunction (2.8%) 

Ureteric stenosis (8%) 

Laboratory anomalies worsen from baseline 

Lymphopenia (2.9%) 

Hypoalbuminemia (2.8%) 

eGFR (10%) 

Thrombocytopenia (2.8%) 

Hyperkalemia (1.4%) 

Black Box Warning

Black box warning: 

None 

Contraindication / Caution

Contraindications/caution: 

Contraindications: 

• Hypersensitivity or Allergy: Patients with known hypersensitivity or allergy to mitomycin or its components should not receive mitomycin pyelocalyceal. 
• Severe Bone Marrow Suppression: mitomycin can cause bone marrow suppression, reducing blood cell counts (red blood cells, white blood cells, and platelets).  
• Impaired Renal Function: Since mitomycin is eliminated from the body primarily through the kidneys, patients with severe renal impairment or kidney failure may be at a higher risk of drug accumulation and toxicity.  

Caution: 

• Local Irritation and Injury: mitomycin is a cytotoxic agent, and its direct contact with normal urothelial tissues during administration can cause local irritation and injury.  
• Risk of Tissue Perforation: The procedure of mitomycin pyelocalyceal may involve using medical instruments, such as catheters or endoscopes, to deliver the drug.  
• Potential for Systemic Absorption: While the localized administration of mitomycin aims to minimize systemic exposure, some drug absorption is still possible into the bloodstream.  
• Bone Marrow Suppression: mitomycin can cause bone marrow suppression, reducing blood cell counts. 

Pregnancy / Lactation

Pregnancy consideration: Due to findings from animal studies and its mechanism of action, it has the potential to cause harm to the developing fetus.  

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or 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: 

• Correlation with Guanine and Cytosine Content:  The mitomycin-induced cross-linking degree correlates with the guanine and cytosine content in the DNA. The presence of guanine and cytosine bases facilitates the formation of cross-links because the drug’s reactive intermediates preferentially react with these bases. Therefore, DNA sequences rich in guanine and cytosine are more susceptible to mitomycin-induced cross-linking. 
• Suppression of RNA and Protein Synthesis: At high concentrations of mitomycin, the drug’s effects extend beyond inhibiting DNA synthesis. It can also suppress cellular RNA and protein synthesis.  

Pharmacodynamics:  

The pharmacodynamics of mitomycin pyelocalyceal: 

• DNA Cross-Linking: The primary pharmacodynamic effect of mitomycin is the formation of covalent cross-links between DNA strands. Once activated, mitomycin produces reactive intermediates that specifically target and bind to guanine bases in the DNA. This leads to the formation of interstrand cross-links, which inhibit DNA replication and transcription.  
• Cell Cycle Arrest: The cross-linking of DNA by mitomycin triggers cell cycle arrest at various stages, primarily in the late S and early G2 phases. This cell cycle disruption prevents cancer cells from dividing and increasing, contributing to the drug’s antineoplastic effects. 
• Selectivity for Cancer Cells: mitomycin’s cytotoxic effects are not entirely selective; it can also affect normal cells to some extent. However, its use as a localized treatment (pyelocalyceal administration) allows for targeted delivery of the drug to the site of the urothelial carcinoma. This localization minimizes exposure to healthy tissues in other body parts, reducing systemic side effects compared to systemic administration. 
• Anti-angiogenic Activity: mitomycin has shown some anti-angiogenic properties, which can inhibit the formation of new blood vessels that tumours need to grow and spread. This additional mechanism contributes to its anticancer effects. 
• Immunomodulatory Effects: mitomycin has been observed to have immunomodulatory effects, which can impact the body’s immune response to cancer cells. mitomycin may enhance the body’s ability to recognize and attack cancer cells by influencing the immune system. 

Pharmacokinetics: 

Absorption 

Peak plasma concentration: 6.24 ng/mL (2.43-12.8 ng/mL). after localized administration within the pyelocalyceal region, mitomycin is absorbed into the bloodstream and reaches peak plasma concentration. 

Distribution 

It is distributed to various tissues via the bloodstream, including the kidney and other organs. 

The drug’s distribution is influenced by blood flow, tissue permeability, and protein binding. 

Metabolism 

mitomycin is primarily metabolized in the liver. The liver processes the drug into biologically inactive or less active metabolites than the parent compound. 

Elimination and Excretion 

After administration into the pyelocalyceal region, mitomycin forms a semisolid gel. This gel gradually dissolves and releases the drug into the urine. Normal kidney urine flow facilitates the elimination of mitomycin over 4-6 hours. A portion (approximately 10%) of the drug is excreted unchanged in the urine. 

Adminstartion

Administration: 

Pyelocalyceal administration 

• Not for topical, oral, or intravenous use  
• Tell the patient to take 1.3 g of sodium bicarbonate orally the night before, the morning of, and 30 minutes before each instillation.  
• Utilizing an Uroject12 Lever, a ureteral catheter, and a Luer lock syringe with a moulded Luer lock connector, administer as a cold solution.  
• It will turn into a viscous liquid for instillation once chilled at -3°C to 5°C (27-41°F), and it is stable for up to an extra hour after that.  
• Immediately after it becomes a thick liquid, inject. 

Storage 

• Keep items in cartons at 20 to 25 °C (68 to 77 °F); excursions are allowed to 15 to 30 °C (59 to 86 °F). 
• Avoid temperatures above 40 °C (104 °F). 

Patient Information Leaflet

Patient information leaflet 

Generic Name: mitomycin pyelocalyceal 

Why do we use mitomycin pyelocalyceal? 

mitomycin pyelocalyceal is primarily used to treat superficial urothelial carcinoma within the renal pelvis and calyces of the kidney. This localized administration of mitomycin is specifically targeted to treat early-stage and low-grade tumors in the pyelocalyceal region.  

• Superficial Urothelial Carcinoma: mitomycin pyelocalyceal is an effective treatment option for superficial urothelial carcinoma, also known as transitional cell carcinoma, located within the renal pelvis and calyces of the kidney. This type of cancer is confined to the inner lining of the kidney and has not invaded deeper into the kidney tissue.  
• Low-Grade and Early-Stage Tumors: mitomycin pyelocalyceal is particularly suitable for low-grade and early-stage tumors in the pyelocalyceal region. These tumors are usually less aggressive and have a better prognosis.  
• Minimally Invasive Treatment: mitomycin pyelocalyceal is administered through minimally invasive procedures, such as endoscopy or ureteroscopy, which involve inserting medical instruments through the urinary tract. This approach offers patients a less invasive treatment option, leading to shorter hospital stays, quicker recovery times, and reduced discomfort compared to traditional open surgeries. 
• Adjuvant Therapy: mitomycin pyelocalyceal can be used as adjuvant therapy after surgically removing urothelial carcinoma or other localized treatments.  
• Palliative Care: In some cases, mitomycin pyelocalyceal may be used as palliative care for patients with advanced urothelial carcinoma that cannot be entirely removed by surgery or has spread to other body parts.