Hycamtin

Unless your doctor tells you otherwise, continue your normal diet.

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Do not receive a "live" vaccine while using topotecan, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Topotecan may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

This medicine can pass into body fluids (urine, feces, vomit). Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with topotecan, especially:

• filgrastim, pegfilgrastim, or sargramostim; or
• cisplatin, carboplatin or oxaliplatin.

This list is not complete. Other drugs may interact with topotecan, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Topotecan is usually given once daily for 5 days in a row. This treatment is then repeated every 21 days, usually for at least 4 treatments. It may take several weeks for your body to respond to the medication.

Topotecan capsules are taken by mouth. You may need to take two different colored capsules at one time. Make sure you know the difference between capsules because one contains 4 times as much topotecan as the other, even though they may look the same in size.

Take the topotecan capsule with a full glass (8 ounces) of water. You may take the medicine with or without food.

If you vomit after taking a topotecan capsule, do not take another dose that same day. Call your doctor for instructions.

Do not crush or break a topotecan capsule, or use a capsule that has been accidentally broken. The medicine from a broken capsule can be dangerous if it gets in your eyes or on your skin. If this occurs, wash your skin with soap and water or rinse the eyes for at least 15 minutes with plain water. Ask your doctor or pharmacist how to safely handle and dispose of a broken tablet or capsule.

Store topotecan capsules in the refrigerator and protect them from light.

Topotecan injection is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting. Topotecan must be given slowly, and the IV infusion can take up to 30 minutes to complete.

Tell your doctor right away if any of this medicine gets on your skin during the injection. If this does happen, the exposed skin should be rinsed thoroughly with soap and warm water.

Topotecan can lower blood cells that help your body fight infections and help your blood to clot. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood may need to be tested often.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Call your doctor for instructions if you miss any of your topotecan doses.

Hycamtin is a prescription medication used to treat small cell lung cancer, ovarian cancer, and cervical cancer. Hycamtin belongs to a group of drugs called topoisomerase I inhibitors, which kill cancer cells.

This medication comes in capsule form and in an injectable form. The capsules are taken by mouth, once daily for 5 days, every 3 weeks. The injectable form is given directly into a vein (IV) usually once daily (for 30 minutes) for 3 to 5 days every 21 days (for a certain number of cycles).

Common side effects include nausea, diarrhea, and hair loss. 

Hycamtin is a prescription medication used to treat small cell lung cancer, ovarian cancer, and cervical cancer.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Do not receive a "live" vaccine while using topotecan, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you. Live vaccines include measles, mumps, rubella (MMR), oral polio, typhoid, chickenpox (varicella), BCG (Bacillus Calmette and Guérin), and nasal flu vaccine.

Topotecan may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

You should not use topotecan if you have severe bone marrow depression.

Topotecan can lower blood cells that help your body fight infections and help your blood to clot. You may get an infection or bleed more easily. Call your doctor if you have unusual bruising or bleeding, or signs of infection (fever, chills, body aches).

Call your doctor for instructions if you miss any of your topotecan doses.

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Do not receive a "live" vaccine while using topotecan, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Topotecan may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

This medicine can pass into body fluids (urine, feces, vomit). Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Storage

Oral

20–25°C (may be exposed to 15–30°C); protect from light.c

Parenteral

20–25°C; protect from light.1 Use immediately after reconstitution.1 Following dilution with infusion solution, use drug within 24 hours.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Black, tarry stools
• bleeding gums
• blood in the urine or stools
• chest pain
• chills
• cough
• fever
• lower back or side pain
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• shortness of breath
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• swollen glands
• troubled breathing with exertion
• unusual bleeding or bruising
• unusual tiredness or weakness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Diarrhea
• hair loss or thinning of the hair
• lack or loss of strength
• loss of appetite
• nausea
• vomiting
• weight loss

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Ovarian Cancer

Hycamtin for injection, as a single agent, is indicated for the treatment of patients with metastatic carcinoma of the ovary after disease progression on or after initial or subsequent chemotherapy.

Small Cell Lung Cancer

Hycamtin for injection, as a single agent, is indicated for the treatment of patients with small cell lung cancer with platinum-sensitive disease who progressed at least 60 days after initiation of first‑line chemotherapy.

Cervical Cancer

Hycamtin for injection in combination with cisplatin is indicated for the treatment of patients with Stage IV-B, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment.

Hycamtin is contraindicated in patients who have a history of severe hypersensitivity reactions to topotecan.

The following serious adverse reactions are described below and elsewhere in the labeling:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Ovarian Cancer

Table 1 shows the Grade 3/4 hematologic and major non‑hematologic adverse reactions in the topotecan/paclitaxel comparator trial in ovarian cancer.

Table 1. Adverse Reactions Experienced by ≥5% of Ovarian Cancer Patients Randomized to Receive Hycamtin or Paclitaxel

a Death related to sepsis occurred in 2% of patients receiving Hycamtin and 0% of patients receiving paclitaxel.

b Pain includes body pain, skeletal pain, and back pain.

Small Cell Lung Cancer

Table 2 shows the Grade 3/4 hematologic and major non‑hematologic adverse reactions in the topotecan/CAV (cyclophosphamide‑doxorubicin‑vincristine) comparator trial in small cell lung cancer.

Table 2. Adverse Reactions Experienced by ≥5% of Small Cell Lung Cancer Patients Randomized to Receive Hycamtin or CAV

a Death related to sepsis occurred in 3% of patients receiving Hycamtin and 1% of patients receiving CAV.

b Pain includes body pain, skeletal pain, and back pain.

Hepatobiliary Disorders in Ovarian and Small Cell Lung Cancer Patients Receiving Hycamtin: Based on the combined experience of 453 patients with metastatic ovarian carcinoma, and 426 patients with small cell lung cancer treated with Hycamtin, Grade 1 transient elevations in hepatic enzymes occurred in 8% of patients. Grade 3/4 elevations occurred in 4%. Grade 3/4 elevated bilirubin occurred in less than 2% of patients.

Cervical Cancer

In the comparative trial with Hycamtin plus cisplatin versus cisplatin in patients with cervical cancer, the most common dose-limiting adverse reaction was myelosuppression. Table 3 shows the hematologic and non‑hematologic adverse reactions in patients with cervical cancer.

Table 3. Adverse Reactions Experienced by ≥5% of Patients with Cervical Cancer Randomized to Receive Hycamtin plus Cisplatin or Cisplatin Monotherapy (Between-Arm Difference ≥2%)a

a Includes patients who were eligible and treated.

b Data were collected using NCI Common Toxicity Criteria, v. 2.0.

c Grades 1 through 4 only. There were 3 patients who experienced deaths with investigator-designated attribution. The first patient experienced a Grade 5 hemorrhage in which the drug-related thrombocytopenia aggravated the event. A second patient experienced bowel obstruction, cardiac arrest, pleural effusion, and respiratory failure which were not treatment-related but probably aggravated by treatment. A third patient experienced a pulmonary embolism and adult respiratory distress syndrome; the latter was indirectly treatment-related.

d Constitutional includes fatigue (lethargy, malaise, asthenia), fever (in the absence of neutropenia), rigors, chills, sweating, and weight gain or loss.

e Pain includes abdominal pain or cramping, arthralgia, bone pain, chest pain (non-cardiac and non-pleuritic), dysmenorrhea, dyspareunia, earache, headache, hepatic pain, myalgia, neuropathic pain, pain due to radiation, pelvic pain, pleuritic pain, rectal or perirectal pain, and tumor pain.

f High-level terms were included if the between-arm difference was ≥10%.

Postmarketing Experience

The following reactions have been identified during postmarketing use of Hycamtin. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Hycamtin.

Blood and Lymphatic System Disorders

Severe bleeding (in association with thrombocytopenia) [see Warnings and Precautions (5.1)].

Immune System Disorders

Allergic manifestations, anaphylactoid reactions.

Gastrointestinal Disorders

Abdominal pain potentially associated with neutropenic enterocolitis [see Warnings and Precautions (5.2)].

Pulmonary Disorders

Interstitial lung disease [see Warnings and Precautions (5.3)].

Skin and Subcutaneous Tissue Disorders

Angioedema, severe dermatitis, severe pruritus.

General Disorders and Administration Site Conditions

Extravasation [see Warnings and Precautions (5.5)].

Overdoses (up to 10-fold of the prescribed dose) occurred in patients treated with intravenous topotecan. The primary complication of overdosage is bone marrow suppression. The observed signs and symptoms of overdose are consistent with the known adverse reactions associated with Hycamtin for intravenous use [see Adverse Reactions (6.1, 6.2)]. In addition, elevated hepatic enzymes and mucositis have been reported following overdose. One patient received a single dose of 40 mg/m2 of intravenous topotecan and developed gastrointestinal toxicity, skin toxicity, and myelosuppression leading to septic shock. Another patient received a single dose of 35 mg/m2 and experienced severe, reversible neutropenia.

There is no known antidote for overdosage with Hycamtin. If an overdose is suspected, monitor the patient closely for bone marrow suppression and institute supportive-care measures (such as the prophylactic use of G-CSF and antibiotic therapy) as appropriate.

Use is contraindicated. (AU) The manufacturer makes no recommendation regarding use during pregnancy. (UK, US) AU TGA pregnancy category: D US FDA pregnancy category: D Comments: -If the patient is pregnant or becomes pregnant during therapy, they should be advised of the potential hazards to the fetus. -Women of childbearing potential should use highly effective contraception during and for at least one month after treatment; males should use contraception during and for 3 months after treatment.

This drug caused embryolethality, fetotoxicity, and teratogenicity in animal models; embryo-fetal toxicity occurred at doses less than clinical doses in humans. Teratogenic effects included effects on the eye, brain, skull, and vertebrae. There are no controlled data in human pregnancy. AU TGA pregnancy category D: Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human fetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details. US FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.