Topokebir
Topokebir Uses, Dosage, Side Effects, Food Interaction and all others data.
Topokebir 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. Topokebir 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).
Topokebir 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, Topokebir acts as an uncompetitive inhibitor.
Topokebir, 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. Topokebir 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 | Topokebir |
| Availability | Prescription only |
| Generic | Topotecan |
| Topotecan Other Names | Topotecan, Topotecane, Topotecanum |
| Related Drugs | methotrexate, Keytruda, carboplatin, pembrolizumab, fluorouracil, doxorubicin, cisplatin, paclitaxel, cyclophosphamide, Avastin |
| Weight | 4mg |
| Type | Injection |
| Formula | C23H23N3O5 |
| Weight | Average: 421.4458 Monoisotopic: 421.163770861 |
| Protein binding | 35% |
| Groups | Approved, Investigational |
| Therapeutic Class | Cytotoxic Chemotherapy |
| Manufacturer | Oncogene Pharmaceuticals Karachi |
| Available Country | Pakistan |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Ovarian Cancer: Topokebir 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: Topokebir 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: Topokebir 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.
Topokebir 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 Topokebir works
Topokebir 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. Topokebir 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).
Topokebir 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, Topokebir acts as an uncompetitive inhibitor.
Dosage
Topokebir dosage
Verify dose usingbody surface areaprior to dispensing. Recommended dosage should generally not exceed 4 mg intravenously
Ovarian Cancer: The recommended dose of Topokebir 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 Topokebir 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 Topokebir 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.
Topokebir Drug Interaction
Moderate: paclitaxel protein-bound, doxorubicin, bevacizumabUnknown: fluticasone / salmeterol, naratriptan, aspirin, loratadine, sulfamethoxazole / trimethoprim, docusate, prochlorperazine, dexamethasone, meperidine, ethanol, albuterol, topiramate, tramadol, acetaminophen, cholecalciferol, ondansetron, cetirizine
Topokebir Disease Interaction
Major: infections, bleeding disorders, myelosuppression, renal dysfunctionModerate: diarrhea, interstitial lung disease
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 Topokebir
Topokebir contains Topotecan see full prescribing information from innovator Topokebir Monograph, Topokebir MSDS, Topokebir FDA label
FAQ
What is Topokebir used for?
Topokebir 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 Topokebir?
Topokebir is well tolerated with an acceptable toxicity profile, with myelosuppression as the dose limiting toxicity.
What are the common side effects of Topokebir?
The common side effects of Topokebir are include; Nausea, vomiting, constipation, diarrhea, abdominal pain, weakness, tiredness, or mouth sores may occur.
Is Topokebir safe during pregnancy?
Topokebir 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 Topokebir if you are pregnant. You may need to have a negative pregnancy test before starting this treatment.
Is Topokebir safe during breastfeeding?
Topokebir is contraindicated during breastfeeding.
How does Topokebir 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 Topokebir 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 Topokebir given?
The oral dose is taken once a day for 5 days and is repeated every 21 days. The amount of Topokebir 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 Topokebir cause hair loss?
Hair loss is seen with Topokebir, but some patients do experience less hair loss than others.
How do you administer Topokebir?
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 Topokebir cause diarrhea?
Topokebir 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 Topokebir?
Topokebir 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 Topokebir?
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 Topokebir?
If you take too much Topokebir, 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 Topokebir?
Avoid driving or hazardous activity until you know how this medicine will affect you.
