Topotecan

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it in the refrigerator and protect it from light.

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Black Box Warnings

Administer only to patients with baseline neutrophil counts of 1500 cells/mm³or higher and a platelet count of 100,000 cells/mm³ or higher

To assess the occurrence of bone marrow suppression, blood cell counts should be monitored

Contraindications

Hypersensitivity reactions to drug or any components

Cautions

Administer to patients with bone marrow suppression only if patient has adequate bone marrow reserves; monitor peripheral blood counts and adjust dose as needed

PO: Do NOT redose if ANC <1500/mm³; Plt 100,000 <mm³; Hgb <9 g/dL

Avoid use in pregnancy; can cause fetal harm; advise women of potential risk to fetus

Neutropenia: pancytopenia has been reported

Fatal cases of interstitial lung disease have occurred; permanently discontinue for confirmed ILD

If extravasation occurs, immediately stop administration and institute recommended management procedures; severe cases reported

PO: If patient vomits after taking capsule, do NOT repeat dose

PO: If diarrhea occurs, treat aggressively, potentially life-threatening

Monitor patients presenting with neutropenia, fever and abdominal pain; fatal typhlitis reported in patients with neutropenic enterocolitisas

Monitor patients presenting with cough, fever, dyspnea and/or hypoxia and a histroy of lung disease as fatalities due to interstitial lung disease have been reported

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if topotecan passes into human breast milk or if it can harm your baby. You and your healthcare provider should decide if you will take topotecan or breast feed. You should not do both.

WARNING: Bone Marrow Suppression

Topotecan should be administered only to patients with baseline neutrophil counts of ≥1,500 cells/mm3 and a platelet count ≥100,000 cells/mm3. In order to assess the occurrence of bone marrow suppression, blood cell counts should be monitored.

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).

Usual Adult Dose for Ovarian Cancer:

1.5 mg/m(2) IV over 30 minutes once a day for 5 consecutive days, starting on day 1 of a 21 day course

Comments:
-In the absence of tumor progression, a minimum of 4 courses is recommended because tumor response may be delayed.
-The median time to response was 9 to 12 weeks.
-Recommended dosage should generally not exceed 4 mg.

Use: Metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy.

Usual Adult Dose for Cervical Cancer:

0.75 mg/m(2) IV over 30 minutes on days 1, 2, and 3 of each 21 day cycle

Comments:
-Administer cisplatin 50 mg/m(2) IV on day 1 of each 21 day cycle.
-Consult cisplatin manufacturer product information for administration and hydration guidelines, and for dose adjustments.
-Recommended dosage should generally not exceed 4 mg.

Use: In combination with cisplatin, treatment of stage IVB, recurrent or persistent carcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy.

Usual Adult Dose for Small Cell Lung Cancer:

IV formulation: 1.5 mg/m(2) IV over 30 minutes once a day for 5 consecutive days, starting on day 1 of a 21 day course
Oral capsules: 2.3 mg/m(2) orally once a day for 5 consecutive days, starting on day 1 of a 21 day course (round dose to nearest 0.25 mg)

Duration of therapy: Until disease progression

Comments:
-In the absence of tumor progression, a minimum of 4 courses is recommended because tumor response may be delayed.
-The median time to response was 5 to 7 weeks.
-Recommended IV dosage should generally not exceed 4 mg.
-Do not prescribe a replacement oral capsule dose for emesis.

Uses:
IV formulation: Small cell lung cancer sensitive disease after failure of first-line chemotherapy. Sensitive disease was defined as disease responding to chemotherapy but subsequently progressing at least 60 to 90 days after chemotherapy.
Capsule formulation: Treatment of relapsed small cell lung cancer in patients with a prior complete or partial response and who are at least 45 days from the end of first-line chemotherapy.

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.

(toe poe TEE kan)

• Antineoplastic Agent, Camptothecin
• Antineoplastic Agent, Topoisomerase I Inhibitor

Cervical cancer, recurrent or resistant: Treatment of recurrent or resistant (stage IVB) cervical cancer (in combination with cisplatin) which is not amenable to curative treatment

Ovarian cancer, metastatic: Treatment of metastatic ovarian cancer (as a single agent) after disease progression on or after initial or subsequent chemotherapy

Small cell lung cancer, relapsed:

Injection: Treatment of small cell lung cancer (as a single agent) in patients with platinum-sensitive disease which has progressed at least 60 days after initiation of first-line chemotherapy

Oral: Treatment of relapsed small cell lung cancer in patients with a prior complete or partial response and who are at least 45 days from the end of first-line chemotherapy

Acute myeloid leukemia (induction in older adults)

Data from a retrospective study suggest that topotecan induction may be beneficial for the treatment of AML in older adults [Kantarjian 2006]. Additional data may be necessary to further define the dose and the role of topotecan in this condition.

CNS malignancy, relapsed/refractory

Data from a limited number of patients studied suggest that topotecan may be beneficial for the treatment of recurrent/refractory CNS malignancy in children [Minturn 2011]. Additional data may be necessary to further define the role of topotecan in this condition.

Ewing sarcoma

Data from a phase II study and a retrospective analysis support the use of topotecan in the treatment of Ewing sarcoma [Hunold 2006], [ Saylors 2001]. Additional trials may be necessary to further define the role of topotecan in this condition.

Neuroblastoma, relapsed/refractory

Data from both prospective and retrospective analyses support the use of topotecan in the management of relapsed/refractory neuroblastoma [Ashraf 2013], [ London 2010]. Additional trials may be necessary to further define the role of topotecan in this condition.

Ovarian cancer, metastatic (off-label [weekly] dosing)

Data from a phase II trial supports the use of topotecan as a weekly administration (in addition to the conventional 5-day treatment course) in the treatment of metastatic ovarian cancer [Sehouli 2011]. Additional trials may be necessary to further define the optimal topotecan schedule in this condition.

Primary CNS lymphoma, relapsed or refractory

Data from a phase II trial suggests that topotecan may be beneficial for the treatment of relapsed or refractory primary CNS lymphoma [Voloschin 2008]. Additional trials may be necessary to further define the role of topotecan in this condition.

Rhabdomyosarcoma

Data from a phase II trial supports the use of topotecan in the treatment of metastatic rhabdomyosarcoma [Walterhouse 2004]. Additional trials may be necessary to further define the role of topotecan in this condition.

IV: Administer IVPB over 30 minutes. For combination chemotherapy with cisplatin, administer pretreatment hydration.

Oral: Administer without regard to meals. Swallow whole; do not open, crush, chew, or divide capsule. If vomiting occurs after dose, do not take replacement dose. For patients unable to swallow capsules whole, reconstituted topotecan solution for injection (1 mg/mL concentration) may be mixed with up to 30 mL of acidic fruit juice (eg, apple, orange, grape) immediately prior to oral administration (Daw 2004).