Topotecan

Topotecan is a chemotherapy agent approved across several products and formulations for the following cancers:

• Metastatic ovarian cancer: Hycamtin for injection and Topotecan Hydrochloride for injection are used as a single agent after the cancer has progressed on prior chemotherapy.
• Small cell lung cancer (SCLC) — intravenous: Hycamtin for injection, Topotecan Injection, and Topotecan Hydrochloride for injection are used as a single agent for platinum-sensitive SCLC that progressed at least 60 days after first-line chemotherapy.
• Small cell lung cancer (SCLC) — oral: Hycamtin capsules are approved for relapsed SCLC in patients who had at least a partial response to prior treatment and are at least 45 days out from first-line therapy.
• Cervical cancer: Hycamtin for injection, Topotecan Injection, and Topotecan Hydrochloride for injection are used in combination with cisplatin for Stage IV-B, recurrent, or persistent cervical cancer that cannot be cured with surgery or radiation.

Topotecan targets an enzyme called topoisomerase I. Normally, this enzyme helps unwind the DNA double helix so cells can copy their genetic information and divide. Topotecan locks onto the complex formed between topoisomerase I and DNA, trapping broken DNA strands in a state they can't escape from. During cell division, these trapped breaks become permanent double-strand breaks — damage that most cancer cells cannot repair — ultimately killing the cell.

Because rapidly dividing cells depend most heavily on this process, cancer cells tend to be hit hardest. However, fast-dividing normal cells (like blood-forming cells in the bone marrow) are also affected, which is why low blood counts are the main side effect.

Topotecan is available as an intravenous (IV) infusion and as oral capsules (Hycamtin), and the two forms are used for different approved indications — they are not interchangeable. The IV forms are given by infusion into a vein over 30 minutes, typically on consecutive days within a repeating 21-day treatment cycle; the specific schedule depends on which cancer is being treated and whether topotecan is given alone or with cisplatin. Hycamtin capsules are taken by mouth on a schedule your oncology team sets.

• Your prescriber will determine your dose based on body surface area, kidney function, and blood counts.
• Blood cell counts must be adequate before each treatment course begins.
• Follow your care team's instructions exactly — do not change your dose or schedule on your own.

Topotecan commonly affects the blood and digestive system. The most frequently reported side effects include:

• Neutropenia (very low infection-fighting white blood cells) — affects nearly all patients
• Leukopenia (overall low white blood cell count)
• Anemia (low red blood cells), causing tiredness and weakness
• Thrombocytopenia (low platelets), raising the risk of bruising and bleeding
• Nausea and vomiting
• Hair loss (alopecia)
• Diarrhea or constipation
• Fatigue and fever

Serious reactions requiring prompt medical attention include fever or signs of infection (which may indicate dangerous neutropenia), severe abdominal pain (possible neutropenic colitis), new shortness of breath or cough (possible interstitial lung disease), and severe allergic reactions such as swelling or difficulty breathing.

• Bone marrow suppression: The biggest risk — topotecan can severely lower white blood cells, red blood cells, and platelets. This is the dose-limiting toxicity. Blood counts are monitored throughout treatment and doses adjusted as needed. Treatment-related deaths from neutropenic infection have been reported.
• Neutropenic colitis: Dangerous bowel inflammation can occur when white blood cell counts are very low. Report severe abdominal pain immediately.
• Interstitial lung disease (ILD): Lung inflammation has been reported. Tell your care team about any new cough, shortness of breath, or breathing difficulty.
• Fetal harm: Topotecan can cause miscarriage, birth defects, and fetal death. Effective contraception is required during treatment — and for 6 months (women) or 3 months (men) after the last dose.
• Do not breastfeed during treatment or for 1 week after the last dose.

Topotecan has a few important drug interactions to know about:

• G-CSF (e.g., filgrastim): This white blood cell booster is sometimes used alongside chemotherapy, but starting it too soon after topotecan can actually make the neutropenia last longer. It should not be given until at least 24 hours after the last topotecan dose in a cycle.
• Cisplatin and other cytotoxic chemotherapy drugs: Combining topotecan with cisplatin or other cell-killing agents increases bone marrow suppression significantly — sometimes requiring dose reductions of both drugs. The timing of when cisplatin is given relative to topotecan also matters and is carefully managed by your oncology team.

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

• Tell your doctor if you've ever had a severe allergic reaction (anaphylaxis or anaphylactoid reaction) to topotecan or any of its ingredients — this is a contraindication.
• Topotecan must not be started if your neutrophil (white blood cell) count is too low — your baseline counts will be checked first.
• Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding — topotecan causes fetal harm and must be avoided in pregnancy.
• Women of childbearing potential must use effective contraception during treatment and for 6 months after the last dose.
• Men with a female partner who could become pregnant must use contraception during treatment and for 3 months after the last dose; topotecan may damage sperm.
• Tell your doctor if your kidneys don't work well — reduced kidney function slows topotecan clearance from your body and may require a dose adjustment.
• Older adults: decreased kidney function (common with age) is an important factor in how the body clears topotecan; your care team will account for this.
• Children: safety and effectiveness in pediatric patients have not been established.

Overdoses with intravenous topotecan (up to 10 times the intended dose) have occurred. The main danger is severe bone marrow suppression — extremely low blood counts leading to serious infection. Elevated liver enzymes, mucositis (mouth sores), and gastrointestinal and skin toxicity have also been reported with overdose. There is no specific antidote; treatment focuses on monitoring blood counts closely and using supportive care such as G-CSF and antibiotics as appropriate.

Topotecan's main measurable effect on the body is a drop in white blood cell counts — this is its dose-limiting toxicity, meaning it's the effect that most often requires dose adjustment. As the dose increases, so does the degree of white blood cell suppression. An 80% to 90% drop in white blood cell count at the lowest point (nadir) is typically seen after the first treatment cycle. This suppression does not worsen cumulatively over multiple treatment cycles.

After IV infusion, topotecan is cleared from the body relatively quickly, with a half-life of 2 to 3 hours — meaning the drug level drops by half about every 2 to 3 hours. Only about 35% of the drug binds to proteins in the blood, leaving most of it free to act. The kidneys are the primary route of elimination, which is why reduced kidney function meaningfully slows the drug's clearance and can increase its effects — making dose adjustments necessary for patients with moderate kidney impairment. Liver impairment also reduces clearance somewhat, though patients with mild-to-moderate liver impairment have generally tolerated standard doses.

Store at 20° to 25°C (68° to 77°F) . Protect from light; product is light-sensitive.