Irinotecan 40mg/2ml Inj, 2ml

Irinotecan is a prodrug that is converted by carboxylesterases to its active metabolite, SN-38. SN-38 is a topoisomerase I inhibitor. Topoisomerase I relieves torsional strain in DNA by inducing single-strand breaks. SN-38 binds to the topoisomerase I-DNA complex, preventing re-ligation of the DNA strand breaks. This leads to accumulation of DNA damage, which ultimately triggers apoptosis in rapidly dividing cancer cells.

Important Side Effects to Report to Your Doctor Right Away

Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you experience any of the following symptoms, 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, trouble 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 will not heal.
Fluid and Electrolyte Imbalance: Mood changes, confusion, muscle pain or weakness, abnormal 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 uncontrolled bleeding.
Severe Dizziness or Fainting: Confusion, redness, or irritation of the palms of hands or soles of feet.
Vein Irritation: If the medication leaks from the vein, it may cause irritation, redness, burning, pain, swelling, or fluid leakage at the injection site. Inform your nurse if you experience any of these symptoms.
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 attention immediately if you experience 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 may only have mild side effects, it is 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 any of these side effects bother you, do not improve, or worsen, consult your doctor. It is crucial to stay hydrated to minimize the risk of dehydration. This list is not exhaustive, and you should consult your doctor if you have any questions or concerns about side effects.

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 is also available to provide guidance and support regarding side effects.

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 currently 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 that it is safe to do so in conjunction 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 any activity that requires alertness and clear vision, ensure you understand how this medication affects you.

Individuals with specific genetic types may have a higher risk of developing severe or life-threatening low white blood cell counts. Your doctor may recommend a genetic test before initiating treatment with this medication. If you have 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 increase your risk of bleeding easily. Take precautions to avoid injury, and use a soft-bristled toothbrush and an electric razor for shaving.

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 certain 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 treatment.

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

If you may become pregnant, use effective birth control methods while taking this medication and for six months after the 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 three months after the last dose. If your partner becomes pregnant, inform the doctor right away.

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

• Laxatives: May exacerbate diarrhea.
• Diuretics: May exacerbate dehydration from diarrhea.
• Corticosteroids (dexamethasone): Used as antiemetic, but may worsen hyperglycemia or increase risk of infection.
• Neuromuscular blocking agents (e.g., succinylcholine): Irinotecan can cause cholinergic symptoms, potentially prolonging neuromuscular blockade.

• Antiemetics (e.g., 5-HT3 antagonists): Standard supportive care.

• Diarrhea (onset, frequency, consistency, presence of blood/mucus)
• Fever (especially with chills, sore throat, or other signs of infection)
• Nausea and vomiting
• Abdominal cramping/pain
• Fatigue/weakness
• Hair loss
• Signs of cholinergic syndrome (e.g., rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing, bradycardia, intestinal hyperperistalsis)

Category D. Irinotecan can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose.

L5 (Contraindicated). It is not known whether irinotecan or its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in breastfed infants, breastfeeding is contraindicated during irinotecan treatment and for at least one week after the last dose.

Safety and effectiveness in pediatric patients have not been established. Irinotecan is generally not used in pediatric oncology outside of specific clinical trials for certain rare tumors (e.g., neuroblastoma, rhabdomyosarcoma), where dosing and toxicity profiles may differ significantly from adult mCRC indications.

No overall differences in safety or effectiveness were observed between elderly patients (≥65 years) and younger patients in clinical trials, but greater sensitivity of some older individuals cannot be ruled out. Close monitoring for toxicity, particularly diarrhea and myelosuppression, is recommended due to potential for decreased physiological reserve.

• Pre-medication with antiemetics (e.g., 5-HT3 antagonist with dexamethasone) is crucial to prevent nausea and vomiting.
• Atropine (0.25-1 mg IV/SC) should be readily available to treat acute cholinergic syndrome (early diarrhea, sweating, abdominal cramps, etc.) which can occur during or shortly after infusion.
• Aggressive management of late diarrhea is paramount. Patients should be instructed to start loperamide immediately at the first sign of loose stools (e.g., 4 mg initially, then 2 mg every 2 hours until diarrhea-free for 12 hours, or as directed by physician).
• Patients with UGT1A1*28 allele (homozygous or heterozygous) are at significantly increased risk of severe neutropenia and diarrhea. Dose adjustments or closer monitoring may be warranted based on genotyping results, if available.
• Monitor for signs of infection, especially during periods of neutropenia. Febrile neutropenia is a medical emergency requiring prompt evaluation and broad-spectrum antibiotics.
• Cumulative toxicity can occur, particularly myelosuppression and diarrhea, requiring careful dose adjustments in subsequent cycles.

• Oxaliplatin (another chemotherapy agent used in colorectal cancer, often in FOLFOX regimen)
• 5-Fluorouracil (a pyrimidine analog, often used in combination regimens)
• Capecitabine (oral prodrug of 5-FU)
• Targeted therapies (e.g., bevacizumab, cetuximab, panitumumab, regorafenib, encorafenib, binimetinib) depending on tumor molecular profile and line of therapy.
• Immunotherapy (e.g., pembrolizumab, nivolumab, ipilimumab) for MSI-H/dMMR colorectal cancer.

If your symptoms or health problems persist or worsen, it is essential to contact your doctor for further evaluation and guidance. To ensure safe and effective treatment, never share your medication with others, and do not take medication prescribed to someone else.

Store all medications in a secure location, out of the reach of children and pets, to prevent accidental ingestion. Properly dispose of unused or expired medications by checking with your pharmacist for guidance on the best disposal method. Unless instructed to do so, avoid flushing medications down the toilet or pouring them down the drain, as this can harm the environment. Many communities have drug take-back programs, which your pharmacist can help you locate.

Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about your medication, consult with your doctor, nurse, pharmacist, or other healthcare provider.

In the event of a suspected overdose, immediately contact your local poison control center or seek emergency medical attention. Be prepared to provide critical information, including the name of the medication, the amount taken, and the time it was taken, to ensure prompt and effective treatment.