AJ-Topotecan

AJ-Topotecan Uses, Dosage, Side Effects, Food Interaction and all others data.

AJ-Topotecan has the same mechanism of action as irinotecan and is believed to exert its cytotoxic effects during the S-phase of DNA synthesis. Topoisomerase I relieves torsional strain in DNA by inducing reversible single strand breaks. AJ-Topotecan binds to the topoisomerase I-DNA complex and prevents religation of these single strand breaks. This ternary complex interferes with the moving replication fork, which leads to the induction of replication arrest and lethal double-stranded breaks in DNA. As mammalian cells cannot efficiently repair these double strand breaks, the formation of this ternary complex eventually leads to apoptosis (programmed cell death).

AJ-Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (-1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme–substrate complex, AJ-Topotecan acts as an uncompetitive inhibitor.

AJ-Topotecan, a semi-synthetic derivative of camptothecin (a plant alkaloid obtained from the Camptotheca acuminata tree), is an anti-tumor drug with topoisomerase I-inhibitory activity similar to irinotecan. DNA topoisomerases are enzymes in the cell nucleus that regulate DNA topology (3-dimensional conformation) and facilitate nuclear processes such as DNA replication, recombination, and repair. During these processes, DNA topoisomerase I creates reversible single-stranded breaks in double-stranded DNA, allowing intact single DNA strands to pass through the break and relieve the topologic constraints inherent in supercoiled DNA. The 3'-DNA terminus of the broken DNA strand binds covalently with the topoisomerase enzyme to form a catalytic intermediate called a cleavable complex. After DNA is sufficiently relaxed and the strand passage reaction is complete, DNA topoisomerase reattaches the broken DNA strands to form the unaltered topoisomers that allow transcription to proceed. AJ-Topotecan interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal cells can be affected by the medicine, other effects may also occur. Unlike irinotecan, topotecan is found predominantly in the inactive carboxylate form at neutral pH and it is not a prodrug.

Trade Name AJ-Topotecan
Availability Prescription only
Generic Topotecan
Topotecan Other Names Topotecan, Topotecane, Topotecanum
Related Drugs methotrexate, Keytruda, carboplatin, pembrolizumab, fluorouracil, doxorubicin, cisplatin, paclitaxel, cyclophosphamide, Avastin
Type
Formula C23H23N3O5
Weight Average: 421.4458
Monoisotopic: 421.163770861
Protein binding

35%

Groups Approved, Investigational
Therapeutic Class Cytotoxic Chemotherapy
Manufacturer
Available Country Canada, United States
Last Updated: September 19, 2023 at 7:00 am
AJ-Topotecan
AJ-Topotecan

Uses

Ovarian Cancer: AJ-Topotecan for injection, as a single agent, is used 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: AJ-Topotecan for injection, as a single agent, is used 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: AJ-Topotecan for injection in combination with cisplatin is used for the treatment of patients with Stage IV-B, recurrent, or persistent carcinoma of the cervix not amenable to curative treatment.

AJ-Topotecan is also used to associated treatment for these conditions: Acute Myeloid Leukemia (AML), Ewing's Sarcoma, Refractory Neuroblastoma, Metastatic Rhabdomyosarcoma, Recurrent, IV-B Cervical cancer, Refractory CNS lymphoma, Refractory CNS malignancy, Refractory, metastatic Ovarian cancer, Relapsed Small cell lung cancer

How AJ-Topotecan works

AJ-Topotecan has the same mechanism of action as irinotecan and is believed to exert its cytotoxic effects during the S-phase of DNA synthesis. Topoisomerase I relieves torsional strain in DNA by inducing reversible single strand breaks. AJ-Topotecan binds to the topoisomerase I-DNA complex and prevents religation of these single strand breaks. This ternary complex interferes with the moving replication fork, which leads to the induction of replication arrest and lethal double-stranded breaks in DNA. As mammalian cells cannot efficiently repair these double strand breaks, the formation of this ternary complex eventually leads to apoptosis (programmed cell death).

AJ-Topotecan mimics a DNA base pair and binds at the site of DNA cleavage by intercalating between the upstream (−1) and downstream (+1) base pairs. Intercalation displaces the downstream DNA, thus preventing religation of the cleaved strand. By specifically binding to the enzyme–substrate complex, AJ-Topotecan acts as an uncompetitive inhibitor.

Dosage

AJ-Topotecan dosage

Verify dose usingbody surface areaprior to dispensing. Recommended dosage should generally not exceed 4 mg intravenously

Ovarian Cancer: The recommended dose of AJ-Topotecan is 1.5 mg/m² by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day course.

Small Cell Lung Cancer: The recommended dose of AJ-Topotecan is 1.5 mg/m² by intravenous infusion over 30 minutes daily for 5 consecutive days, starting on Day 1 of a 21-day course.

Cervical Cancer: The recommended dose of AJ-Topotecan is 0.75 mg/m² by intravenous infusion over 30 minutes daily on Days 1, 2, and 3 in combination with cisplatin 50 mg/m² on Day 1, repeated every 21 days.

Add 4 ml of sterile water for inj to the vial containing 4 mg of topotecan in order to obtain a solution with 1 mg/ml of topotecan. The required daily dose is further diluted in a suitable volume (e.g. 50-250 ml) of 5% dextrose or 0.9% sodium chloride inj and infused IV over a period of 30 min. Solution should be prepared immediately before use.

Side Effects

Neutropenia (nadir of white cell count occurs about 9-12 days after admin), thrombocytopenia and anaemia. GI upset, total alopecia, headache, dyspnoea. Fatigue, weakness, malaise, pruritus and hyperbilirubinaemia.

Toxicity

The primary anticipated complication of overdosage would consist of bone marrow suppression.

Precaution

Preexisting bone marrow depression. Frequent monitoring of peripheral blood cell counts during treatment. Do not continue subsequent courses until neutrophils recover to >1000 cells/mm3, platelets recover to >100,000 cells/mm3 and haemoglobin levels recover to 9.0 g/dl (with transfusion if needed). May impair ability to drive or operate machinery.

Interaction

Increased clearance with phenytoin. G-CGF to be given 24 hr after completion of treatment with topotecan as concurrent admin may prolong duration of neutropenia. Increased bone marrow supression with other cytotoxic drugs (e.g. cisplatin) so dose reduction may be needed.

Food Interaction

  • Take with or without food.

Half Life

2-3 hours

Elimination Route

Renal clearance is an important determinant of topotecan elimination. In a mass balance/excretion study in 4 patients with solid tumors, the overall recovery of total topotecan and its N-desmethyl metabolite in urine and feces over 9 days averaged 73.4 ± 2.3% of the administered IV dose. Fecal elimination of total topotecan accounted for 9 ± 3.6% while fecal elimination of N-desmethyl topotecan was 1.7 ± 0.6%.

Pregnancy & Breastfeeding use

Pregnancy category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Contraindication

Severe bone marrow depression (e.g. baseline neutrophil count of <1500 cells/mm3 and platelet count <100,000/mm3). Pregnancy, lactation, severe renal or hepatic impairment.

Special Warning

Renal Impairment:

  • Ovarian carcinoma, Small cell lung cancer: CrCl 20-30: Initial dose 0.75 mg/m2.
  • Cervical cancer: Treatment to be initiated only if serum creatinine ≤1.5 mg/dl.

Hepatic Impairment: Avoid

Acute Overdose

Symptoms: Bone marrow supression.

Storage Condition

Unopened vial: Store at 20-25°C; protect from light. Reconstituted solution: Stable for 24 hr at 20-25°C in ambient light.

Innovators Monograph

You find simplified version here AJ-Topotecan

AJ-Topotecan contains Topotecan see full prescribing information from innovator AJ-Topotecan Monograph, AJ-Topotecan MSDS, AJ-Topotecan FDA label

FAQ

What is AJ-Topotecan used for?

AJ-Topotecan is used to treat small cell lung cancer that was successfully treated with a different chemotherapy medication but has returned no sooner than 45 days after the last dose of the first chemotherapy medication was taken.

How safe is AJ-Topotecan?

AJ-Topotecan is well tolerated with an acceptable toxicity profile, with myelosuppression as the dose limiting toxicity.

What are the common side effects of AJ-Topotecan?

The common side effects of AJ-Topotecan are include; Nausea, vomiting, constipation, diarrhea, abdominal pain, weakness, tiredness, or mouth sores may occur. 

Is AJ-Topotecan safe during pregnancy?

AJ-Topotecan can harm an unborn baby or cause birth defects if the mother or the father is using this medicine. If you are a woman, do not use AJ-Topotecan if you are pregnant. You may need to have a negative pregnancy test before starting this treatment.

Is AJ-Topotecan safe during breastfeeding?

AJ-Topotecan is contraindicated during breastfeeding.

How does AJ-Topotecan work?

It works by blocking a chemical called topoisomerase 1. This chemical helps to separate and repair the DNA in cells when they divide. Cancer cells need to make and repair DNA in order to grow and multiply.

How long does AJ-Topotecan take to work?

This 3-day or 5-day treatment is given again every 21 days until your body responds to the medicine. Each treatment usually takes at least 30 minutes.

How often is AJ-Topotecan given?

The oral dose is taken once a day for 5 days and is repeated every 21 days. The amount of AJ-Topotecan that you will receive depends on many factors, including your height and weight, your general health or other health problems, and the type of cancer or condition being treated.

Does AJ-Topotecan cause hair loss?

Hair loss is seen with AJ-Topotecan, but some patients do experience less hair loss than others.

How do you administer AJ-Topotecan?

The recommended dose administered by intravenous infusion over 30 minutes daily for 5 consecutive days with a 3 week interval between the start of each course.

Does AJ-Topotecan cause diarrhea?

AJ-Topotecan may cause diarrhea, and in some cases it can be severe. Do not take any medicine to treat diarrhea without first checking with your doctor. Diarrhea medicines may make the diarrhea worse or make it last longer.

How long can I take AJ-Topotecan?

AJ-Topotecan is usually given every day for 3 to 5 days. This 3-day or 5-day treatment is given again every 21 days until your body responds to the medicine.

Who should not take AJ-Topotecan?

If you have ever had any unusual or allergic reaction to this medicine. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals.

What happen if I overdose on AJ-Topotecan?

If you take too much AJ-Topotecan, call your local Poison Control Center or seek emergency medical attention right away. Overdose symptoms may include skin rash or other irritation, nausea, vomiting, diarrhea, or mouth sores.

What happens if I miss a dose?

Take the medicine as soon as you can, but skip the missed dose if it is almost time for your next dose. Do not take two doses at one time.

Can I drive atfter taking AJ-Topotecan?

Avoid driving or hazardous activity until you know how this medicine will affect you.

*** Taking medicines without doctor's advice can cause long-term problems.
Share