Irinotecan 20mg/ml Inj, 5ml

Irinotecan is a prodrug that is converted by carboxylesterases to its active metabolite, SN-38. SN-38 inhibits topoisomerase I, an enzyme critical for DNA replication, transcription, and repair. By binding to the topoisomerase I-DNA complex, SN-38 prevents religation of DNA single-strand breaks, leading to accumulation of DNA damage and ultimately apoptosis of cancer cells.

Urgent Side Effects: Seek Medical Help Right Away

Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:

Allergic Reaction: Rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Infection: Fever, chills, severe sore throat, ear or sinus pain, cough, increased sputum production or change in sputum color, painful urination, mouth sores, or a wound that won't heal.
Fluid and Electrolyte Imbalance: Mood changes, confusion, muscle pain or weakness, irregular or rapid heartbeat, severe dizziness or fainting, increased thirst, seizures, extreme fatigue or weakness, decreased appetite, difficulty urinating or changes in urine output, dry mouth, dry eyes, or severe nausea and vomiting.
Kidney Problems: Inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruising or bruising that worsens, or uncontrollable bleeding.
Severe Dizziness or Fainting
Confusion
Redness or Irritation: Redness, irritation, or discomfort on the palms of your hands or soles of your feet. This medication may cause vein irritation, and if it leaks from the vein, it can cause irritation around the injection site. Inform your nurse if you experience redness, burning, pain, swelling, or fluid leakage at the injection site.
Lung Problems: Shortness of breath, difficulty breathing, new or worsening cough, or fever. These symptoms can be life-threatening, so seek medical attention immediately.
Blood Clots: If you have a history of blood clots, inform your doctor. Seek medical help right away if you experience symptoms like chest pain or pressure, coughing up blood, shortness of breath, swelling, warmth, numbness, color changes, or pain in your legs or arms, or difficulty speaking or swallowing.

Other Possible Side Effects

While many people may not experience side effects or only have mild ones, it's essential to be aware of the following:

Hair loss
Dizziness, drowsiness, fatigue, or weakness
Sleep disturbances
Headache
Back pain
Excessive sweating
Weight loss
Gas
Mouth irritation or mouth sores
Constipation
* Nausea, vomiting, stomach pain, and decreased appetite (common side effects that can be managed with your doctor's guidance)

If these side effects bother you, don't improve, or worsen, contact your doctor for advice. It's crucial to stay hydrated to minimize the risk of dehydration. This list is not exhaustive, and if you have concerns about side effects, consult your doctor.

Reporting Side Effects

You can report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch. Your doctor can also provide guidance on managing side effects and offer medical advice.

Before Taking This Medication: Important Information to Share with Your Doctor

It is essential to inform your doctor about the following:

Any allergies you have, including allergies to this medication, its components, or other substances. Be sure to describe the symptoms you experienced.
If you are undergoing dialysis, discuss this with your doctor.
Any medications you are taking, including prescription and over-the-counter drugs, natural products, and vitamins, that may interact with this medication. Certain medications used to treat HIV, infections, seizures, and other conditions should not be taken with this drug.
If you are breastfeeding, as you should not breastfeed while taking this medication and for 1 week after your last dose.

Please note that this is not an exhaustive list of all potential interactions. To ensure your safety, it is crucial to inform your doctor and pharmacist about all your medications, health problems, and any other relevant information. Before starting, stopping, or changing the dose of any medication, consult with your doctor to confirm it is safe to do so with this medication.

It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.

Before operating a vehicle or engaging in activities that require alertness and clear vision, wait until you understand how this medication affects you.

Certain genetic factors may increase your risk of developing severe or life-threatening low white blood cell counts. Your doctor may recommend a genetic test before starting this medication to assess this risk. If you have questions or concerns, discuss them with your doctor.

While taking this medication, you may be more susceptible to infections. To minimize this risk, practice good hygiene by washing your hands frequently, and avoid close contact with individuals who have infections, colds, or flu, as some infections can be life-threatening.

This medication may also increase your risk of bleeding easily. Be cautious and take steps to avoid injury. Use a soft-bristled toothbrush and an electric razor to reduce the risk of bleeding.

Regular blood tests will be necessary to monitor your condition. Adhere to the schedule recommended by your doctor and discuss any concerns or questions you may have.

Before receiving any vaccinations, consult with your doctor, as some vaccines may not be effective or may increase the risk of infection when taken with this medication.

If you are 65 years or older, use this medication with caution, as you may be more prone to experiencing side effects.

This medication may affect fertility, potentially leading to difficulties in becoming pregnant or fathering a child. If you plan to conceive, discuss this with your doctor before starting the medication.

This medication can cause harm to an unborn baby. A pregnancy test will be conducted before initiating treatment to confirm that you are not pregnant.

If you may become pregnant, use effective birth control methods while taking this medication and for 6 months after your last dose. If you become pregnant, notify your doctor immediately.

If your partner may become pregnant, use birth control while taking this medication and for 3 months after your last dose. If your partner becomes pregnant, contact the doctor right away.

• Strong CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin, St. John's Wort): May significantly decrease exposure to irinotecan and SN-38, reducing efficacy. Avoid concomitant use.
• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice): May significantly increase exposure to irinotecan and SN-38, increasing toxicity. Avoid concomitant use.
• UGT1A1 inhibitors (e.g., atazanavir): May increase SN-38 exposure, increasing toxicity. Avoid concomitant use.

• Laxatives: May exacerbate diarrhea. Avoid during treatment, especially around infusion.
• Diuretics: May increase risk of dehydration from diarrhea.
• Neuromuscular blocking agents: Irinotecan has anticholinesterase activity, potentially prolonging neuromuscular blockade of succinylcholine and antagonizing non-depolarizing agents. Use with caution.
• Corticosteroids (dexamethasone): May increase risk of hyperglycemia and infection, and potentially exacerbate diarrhea.

• Antidiarrheals (e.g., loperamide): Essential for managing late diarrhea, but excessive use without medical guidance can mask severe toxicity.

• Diarrhea (onset, frequency, severity, consistency)
• Nausea and vomiting
• Abdominal pain/cramping
• Fever or signs of infection (e.g., chills, sore throat)
• Fatigue/weakness
• Hair loss (alopecia)
• Signs of cholinergic syndrome (diaphoresis, abdominal cramping, bradycardia, rhinitis, lacrimation, salivation, miosis)
• Mucositis/stomatitis

Irinotecan is classified as Pregnancy Category D. It can cause fetal harm when administered to a pregnant woman. Based on its mechanism of action and animal studies, it is expected to cause serious adverse developmental effects. Avoid use during pregnancy.

Irinotecan and its active metabolite SN-38 are excreted in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is contraindicated during treatment with irinotecan and for at least one month after the last dose.

Safety and effectiveness have not been established in pediatric patients. While investigational in some pediatric cancers, dosing is highly variable and toxicity profiles can differ. Use only in specialized centers with extensive experience.

No overall differences in safety or effectiveness were observed between elderly and younger patients in clinical trials, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients may be more susceptible to severe diarrhea and myelosuppression. Close monitoring and careful dose adjustments are recommended.

• The most critical toxicities are severe delayed diarrhea and myelosuppression (neutropenia).
• Patients with UGT1A1*28 allele (homozygous or heterozygous) are at significantly increased risk for severe neutropenia and diarrhea due to reduced SN-38 glucuronidation. Consider UGT1A1 genotyping, especially for patients receiving higher doses or those with prior severe toxicities.
• Early diarrhea (within 24 hours of infusion) is typically cholinergic and responds to atropine. Late diarrhea (>24 hours) is secretory and requires aggressive management with high-dose loperamide (e.g., 4 mg initially, then 2 mg every 2 hours until diarrhea-free for 12 hours, or as directed by physician).
• Prophylactic loperamide is generally not recommended, but patients should be instructed to start it at the first sign of loose stools.
• Febrile neutropenia is a medical emergency requiring immediate hospitalization and broad-spectrum antibiotics.
• Hydration is crucial, especially with diarrhea. IV fluids may be necessary for severe dehydration.
• Monitor liver function closely, as hepatic impairment significantly increases SN-38 exposure and toxicity.
• Irinotecan is often used in combination regimens (e.g., FOLFIRI) for metastatic colorectal cancer.

• Other cytotoxic chemotherapy agents (e.g., 5-fluorouracil, oxaliplatin, capecitabine)
• Targeted therapies (e.g., bevacizumab, cetuximab, panitumumab, regorafenib, encorafenib/binimetinib for BRAF-mutated CRC)
• Immunotherapy (e.g., pembrolizumab, nivolumab for MSI-H/dMMR colorectal cancer)
• Surgical resection
• Radiation therapy

If your symptoms or health problems persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, do not share your medication with others, and never take someone else's medication. Store all medications in a secure location, out of reach of children and pets, to prevent accidental ingestion. Properly dispose of unused or expired medications by checking with your pharmacist for guidance, as some communities have drug take-back programs. Unless instructed to do so, avoid flushing medications down the toilet or pouring them down the drain. If you have questions about disposing of medications, consult your pharmacist. Additionally, some medications may come with a separate patient information leaflet, which can be obtained from your pharmacist. If you have any concerns or questions about your medication, discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. Be prepared to provide information about the medication taken, the amount, and the time it occurred.