Irinotecan 20mg/ml Inj, 15ml

Irinotecan is a prodrug that is converted by carboxylesterase enzymes to its active metabolite, SN-38. SN-38 is a topoisomerase I inhibitor. Topoisomerase I is an enzyme that relieves torsional strain in DNA during replication and transcription by inducing transient single-strand breaks. SN-38 binds to the topoisomerase I-DNA complex, preventing re-ligation of the DNA strand. This leads to DNA damage (single- and double-strand breaks) during DNA replication, ultimately triggering apoptosis and inhibiting cell proliferation.

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, 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 or change in color of sputum, pain while urinating, mouth sores, or a wound that will not heal.
Fluid and Electrolyte Problems: Mood changes, confusion, muscle pain or weakness, fast or abnormal heartbeat, severe dizziness or fainting, increased thirst, seizures, feeling extremely tired or weak, decreased appetite, inability to urinate or changes in urine output, dry mouth, dry eyes, or severe stomach upset or vomiting.
Kidney Problems: Inability to urinate, changes in urine output, blood in the urine, or sudden weight gain.
Bleeding: Vomiting or coughing up blood, vomit that resembles coffee grounds, blood in the urine, black, red, or tarry stools, bleeding from the gums, abnormal vaginal bleeding, unexplained bruises or bruises that enlarge, or uncontrolled bleeding.
Severe Dizziness or Fainting: Sudden loss of balance or consciousness.
Confusion: Disorientation or difficulty thinking clearly.
Skin Irritation: Redness or irritation on the palms of hands or soles of feet.
Vein Irritation: If the medication leaks from the vein, it may cause redness, burning, pain, swelling, or fluid leakage around 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: Chest pain or pressure, coughing up blood, shortness of breath, swelling, warmth, numbness, color changes, or pain in a leg or arm, or difficulty speaking or swallowing. If you have a history of blood clots, inform your doctor and seek medical attention if you experience any of these symptoms.

Other Possible Side Effects

While many people may not experience side effects or may only have mild symptoms, it is essential to be aware of the following possible side effects:

Hair loss
Dizziness, drowsiness, fatigue, or weakness
Sleep disturbances
Headache
Back pain
Excessive sweating
Weight loss
Gas
Mouth irritation or mouth sores
Constipation
Stomach upset, vomiting, stomach pain, or 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 become severe, contact your doctor for advice. It is also crucial to stay hydrated to minimize the risk of dehydration.

Reporting Side Effects

This list is not exhaustive, and you may experience other side effects not mentioned here. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.

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 allergic reaction you experienced, including any symptoms.
If you are undergoing dialysis, discuss this with your doctor to determine the best course of action.
Any medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. Certain medications, such as those used to treat HIV, infections, seizures, and other conditions, may interact with this medication and should be avoided. There are numerous medications that are contraindicated with this drug, so it is crucial to disclose all medications you are taking.
If you are breastfeeding, as you should not breastfeed while taking this medication and for 1 week after your last dose.

This is not an exhaustive list of all potential interactions with this medication. Therefore, it is vital to inform your doctor and pharmacist about all your medications (prescription and OTC), natural products, vitamins, and health problems to ensure safe use. Do not initiate, discontinue, or modify the dosage of any medication without first consulting your doctor to verify 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 engaging in activities that require alertness or clear vision, such as driving, wait until you understand how this drug 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. Be cautious and avoid injuries. Use a soft-bristled toothbrush and an electric razor to reduce the risk of bleeding.

Regular blood tests will be necessary, as directed by your doctor. Consult with your doctor regarding any questions or concerns 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 harm 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 during treatment 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 during treatment and for 3 months after your 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 irinotecan and SN-38, reducing efficacy.
• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice): May significantly increase exposure to irinotecan and SN-38, increasing toxicity (especially myelosuppression and diarrhea).
• 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 for antiemesis, but may worsen hyperglycemia or increase risk of infection in combination with myelosuppression.
• Neuromuscular blocking agents (e.g., succinylcholine): Irinotecan may prolong neuromuscular blockade due to anticholinesterase activity.

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

• Diarrhea (frequency, consistency, presence of blood/mucus)
• Fever (especially with neutropenia)
• Signs of infection (sore throat, chills, cough, painful urination)
• Nausea and vomiting
• Abdominal pain/cramping
• Fatigue/weakness
• Hair loss
• Mucositis/stomatitis
• Symptoms of cholinergic syndrome (sweating, abdominal cramps, bradycardia, rhinitis, lacrimation, salivation, flushing)

Irinotecan can cause fetal harm when administered to a pregnant woman. It is classified as Pregnancy Category D. Advise pregnant women of the potential risk to the 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.

It is not known whether irinotecan or its metabolites are excreted in human milk. Because of the potential for serious adverse reactions in breastfed infants, breastfeeding is contraindicated during treatment with irinotecan and for 1 month after the last dose.

Safety and effectiveness in pediatric patients have not been established. Limited studies in pediatric solid tumors have shown significant toxicity without clear efficacy. Use is generally not recommended outside of specific clinical trials.

No overall differences in safety or effectiveness were observed between elderly patients (≥65 years) and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients may be more susceptible to severe diarrhea and myelosuppression, requiring careful monitoring and potential dose adjustments.

• Irinotecan is notorious for causing two types of diarrhea: early (acute) and delayed. Early diarrhea occurs during or shortly after infusion and is cholinergic in nature, often managed with atropine. Delayed diarrhea occurs 24 hours or more after infusion and can be severe and life-threatening; it requires aggressive management with high-dose loperamide.
• Patients with genetic variations in UGT1A1 (e.g., UGT1A1*28 homozygotes) have reduced metabolism of SN-38 and are at significantly increased risk of severe neutropenia and diarrhea. Genotyping can help identify these patients, and dose reductions may be necessary.
• Myelosuppression, particularly neutropenia, is a dose-limiting toxicity. Frequent CBC monitoring is essential.
• Hydration is critical, especially with diarrhea. Patients should be educated on signs of dehydration and when to seek medical attention.
• Irinotecan is often used in combination regimens like FOLFIRI (Folinic acid, 5-Fluorouracil, Irinotecan) for metastatic colorectal cancer.

• Oxaliplatin (another chemotherapy agent used in colorectal cancer, often in FOLFOX regimen)
• 5-Fluorouracil (often used in combination with other agents)
• Capecitabine (oral fluoropyrimidine)
• Targeted therapies (e.g., bevacizumab, cetuximab, panitumumab, regorafenib, encorafenib/binimetinib for specific mutations)
• Immunotherapy (e.g., pembrolizumab, nivolumab for MSI-high/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 for 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 information about the medication taken, including the dosage, time of ingestion, and any other relevant details to ensure prompt and effective treatment.