DRUGS & SUPPLEMENTS

Toposar

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Toposar uses


INDICATIONS AND USAGE

Toposar capsules are indicated in the management of the following neoplasms:

Small Cell Lung Cancer

Toposar capsules in combination with other approved chemotherapeutic agents as first line treatment in patients with small cell lung cancer.

CONTRAINDICATIONS

Toposar capsules are contraindicated in patients who have demonstrated a previous hypersensitivity to Toposar or any component of the formulation.

WARNINGS

Patients being treated with Toposar must be frequently observed for myelosuppression both during and after therapy. Myelosuppression resulting in death has been reported. Dose-limiting bone marrow suppression is the most significant toxicity associated with Toposar therapy. Therefore, the following studies should be obtained at the start of therapy and prior to each subsequent cycle of Toposar: platelet count, hemoglobin, white blood cell count and differential. The occurrence of a platelet count below 50,000/mm3 or an absolute neutrophil count below 500/mm3 is an indication to withhold further therapy until the blood counts have sufficiently recovered.

Pregnancy

Toposar can cause fetal harm when administered to a pregnant woman. Toposar has been shown to be teratogenic in mice and rats.

In rats, an intravenous Toposar dose of 0.4 mg/kg/day (about 1/20th of the human dose on a mg/m2 basis) during organogenesis caused maternal toxicity, embryotoxicity, and teratogenicity (skeletal abnormalities, exencephaly, encephalocele and anophthalmia); higher doses of 1.2 mg/kg/day and 3.6 mg/kg/day (about 1/7th and 1/2 of human dose on a mg/m2 basis) resulted in 90% and 100% embryonic resorptions. In mice, a single 1.0 mg/kg (1/16th of human dose on a mg/m2 basis) dose of Toposar administered intraperitoneally on days 6, 7 or 8 of gestation caused embryotoxicity, cranial abnormalities, and major skeletal malformations. An I.P. dose of 1.5 mg/kg (about 1/10th of human dose on a mg/m2 basis) on day 7 of gestation caused an increase in the incidence of intrauterine death and fetal malformations and a significant decrease in the average fetal body weight.

Women of childbearing potential should be advised to avoid becoming pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be warned of the potential hazard to the fetus.

Toposar should be considered a potential carcinogen in humans. The occurrence of acute leukemia with or without a preleukemic phase has been reported in rare instances in patients treated with Toposar alone or in association with other neoplastic agents. The risk of development of a preleukemic or leukemic syndrome is unclear. Carcinogenicity tests with Toposar have not been conducted in laboratory animals.

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PRECAUTIONS

General

In all instances where the use of Toposar is considered for chemotherapy, the physician must evaluate the need and usefulness of the drug against the risk of adverse reactions. Most such adverse reactions are reversible if detected early. If severe reactions occur, the drug should be reduced in dosage or discontinued and appropriate corrective measures should be taken according to the clinical judgment of the physician. Reinstitution of Toposar therapy should be carried out with caution, and with adequate consideration of the further need for the drug and alertness as to possible recurrence of toxicity.

Patients with low serum albumin may be at an increased risk for Toposar associated toxicities.

Drug Interactions

High-dose cyclosporin A resulting in concentrations above 2000 ng/mL administered with oral Toposar has led to an 80% increase in Toposar exposure with a 38% decrease in total body clearance of Toposar compared to Toposar alone.

Laboratory Tests

Periodic complete blood counts should be done during the course of Toposar treatment. They should be performed prior to each cycle of therapy and at appropriate intervals during and after therapy. At least one determination should be done prior to each dose of Toposar.

Renal Impairment

In patients with impaired renal function, the following initial dose modification should be considered based on measured creatinine clearance:


Measured Creatinine Clearance


> 50 mL/min


15 to 50 mL/min


Toposar


100% of dose


75% of dose


Subsequent Toposar dosing should be based on patient tolerance and clinical effect.

Data are not available in patients with creatinine clearances < 15 mL/min and further dose reduction should be considered in these patients.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Toposar has been shown to be mutagenic in Ames assay.

Treatment of Swiss-Albino mice with 1.5 mg/kg I.P. of Toposar on day 7 of gestation increased the incidence of intrauterine death and fetal malformations as well as significantly decreased the average fetal body weight. Maternal weight gain was not affected.

Irreversible testicular atrophy was present in rats treated with Toposar intravenously for 30 days at 0.5 mg/kg/day (about 1/16th of the human dose on a mg/m2 basis).

Pregnancy

Teratogenic Effects

Pregnancy Category D

.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Toposar, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Of more than 600 patients in four clinical studies in the NDA databases who received Toposar or Toposar phosphate in combination with other chemotherapeutic agents for the treatment of small cell lung cancer (SCLC), about one-third were older than 65 years. When advanced age was determined to be a prognostic factor for response or survival in these studies, comparisons between treatment groups were performed for the elderly subset. In the one study (etoposide in combination with cyclophosphamide and vincristine compared with cyclophosphamide and vincristine or cyclophosphamide, vincristine and doxorubicin) where age was a significant prognostic factor for survival, a survival benefit for elderly patients was observed for the Toposar regimen compared with the control regimens. No differences in myelosuppression were seen between elderly and younger patients in these studies except for an increased frequency of WHO Grade III or IV leukopenia among elderly patients in a study of Toposar phosphate or Toposar in combination with cisplatin. Elderly patients in this study also had more anorexia, mucositis, dehydration, somnolence and elevated BUN levels than younger patients.

In five single-agent studies of Toposar phosphate in patients with a variety of tumor types, 34% of patients were age 65 years or more. WHO Grade III or IV leukopenia, granulocytopenia and asthenia were more frequent among elderly patients.

Post-marketing experience also suggests that elderly patients may be more sensitive to some of the known adverse effects of Toposar, including myelosuppression, gastrointestinal effects, infectious complications and alopecia.

Although some minor differences in pharmacokinetic parameters between elderly and nonelderly patients have been observed, these differences were not considered clinically significant.

Toposar and its metabolites are known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

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ADVERSE REACTIONS

The following data on adverse reactions are based on both oral and intravenous administration of Toposar as a single agent, using several different dose schedules for treatment of a wide variety of malignancies.

Hematologic Toxicity

Myelosuppression is dose related and dose limiting, with granulocyte nadirs occurring 7 to 14 days after drug administration and platelet nadirs occurring 9 to 16 days after drug administration. Bone marrow recovery is usually complete by day 20, and no cumulative toxicity has been reported. Fever and infection have also been reported in patients with neutropenia. Death associated with myelosuppression has been reported.

The occurrence of acute leukemia with or without a preleukemic phase has been reported rarely in patients treated with Toposar in association with other antineoplastic agents.

Gastrointestinal Toxicity

Nausea and vomiting are the major gastrointestinal toxicities. The severity of such nausea and vomiting is generally mild to moderate with treatment discontinuation required in 1% of patients. Nausea and vomiting can usually be controlled with standard antiemetic therapy. Mild to severe mucositis/esophagitis may occur. Gastrointestinal toxicities are slightly more frequent after oral administration than after intravenous infusion.

Hypotension

Transient hypotension following rapid intravenous administration has been reported in 1% to 2% of patients. It has not been associated with cardiac toxicity or electrocardiographic changes. No delayed hypotension has been noted. To prevent this rare occurrence, it is recommended that Toposar be administered by slow intravenous infusion over a 30- to 60-minute period. If hypotension occurs, it usually responds to cessation of the infusion and administration of fluids or other supportive therapy as appropriate. When restarting the infusion, a slower administration rate should be used.

Allergic Reactions

Anaphylactic-like reactions characterized by chills, fever, tachycardia, bronchospasm, dyspnea and/or hypotension have been reported to occur in 0.7% to 2% of patients receiving intravenous Toposar and in less than 1% of the patients treated with the oral capsules. These reactions have usually responded promptly to the cessation of the infusion and administration of pressor agents, corticosteroids, antihistamines or volume expanders as appropriate; however, the reactions can be fatal. Hypertension and/or flushing have also been reported. Blood pressure usually normalizes within a few hours after cessation of the infusion. Anaphylactic-like reactions have occurred during the initial infusion of Toposar.

Facial/tongue swelling, coughing, diaphoresis, cyanosis, tightness in throat, laryngospasm, back pain and/or loss of consciousness have sometimes occurred in association with the above reactions. In addition, an apparent hypersensitivity-associated apnea has been reported rarely.

Rash, urticaria, and/or pruritus have infrequently been reported at recommended doses. At investigational doses, a generalized pruritic erythematous maculopapular rash, consistent with perivasculitis, has been reported.

Alopecia

Reversible alopecia, sometimes progressing to total baldness, was observed in up to 66% of patients.

Other Toxicities

The following adverse reactions have been infrequently reported: abdominal pain, aftertaste, constipation, dysphagia, asthenia, fatigue, malaise, somnolence, transient cortical blindness, optic neuritis, interstitial pneumonitis/pulmonary fibrosis, fever, seizure (occasionally associated with allergic reactions), Stevens-Johnson Syndrome, and toxic epidermal necrolysis, pigmentation, and a single report of radiation recall dermatitis.

Hepatic toxicity, generally in patients receiving higher doses of the drug than those recommended, has been reported with Toposar. Metabolic acidosis has also been reported in patients receiving higher doses.

The incidences of adverse reactions in the table that follows are derived from multiple data bases from studies in 2,081 patients when Toposar was used either orally or by injection as a single agent.


ADVERSE DRUG EFFECT


PERCENT RANGE OF REPORTED INCIDENCE


Hematologic toxicity

Leukopenia (less than 1,000 WBC/mm3)

Leukopenia (less than 4,000 WBC/mm3)

Thrombocytopenia (less than 50,000 platelets/mm3)

Thrombocytopenia (less than 100,000 platelets/mm3)

Anemia



3 to 17

60 to 91

1 to 20

22 to 41

0 to 33


Gastrointestinal toxicity

Nausea and vomiting

Abdominal pain

Anorexia

Diarrhea

Stomatitis

Hepatic



31 to 43

0 to 2

10 to 13

1 to 13

1 to 6

0 to 3


Alopecia

Peripheral neurotoxicity

Hypotension

Allergic reaction


8 to 66

1 to 2

1 to 2

1 to 2



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OVERDOSAGE

No proven antidotes have been established for Toposar overdosage.

DOSAGE AND ADMINISTRATION

Toposar Capsules

In small cell lung cancer, the recommended dose of Toposar capsules is two times the IV dose rounded to the nearest 50 mg.

The dosage should be modified to take into account the myelosuppressive effects of other drugs in the combination or the effects of prior x-ray therapy or chemotherapy which may have compromised bone marrow reserve.

Stability

Toposar capsules must be stored under refrigeration 2° to 8°C (36° to 46°F). The capsules are stable for 36 months under such refrigeration conditions.

Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published1-8. There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

HOW SUPPLIED

Toposar Capsules, USP are available containing 50 mg of Toposar, USP.

The 50 mg capsule is an opaque dark pink, soft gelatin capsule printed with E50 in black ink. They are available as follows:

NDC 0378-3266-94

20 Capsules - Unit Dose

Capsules are to be stored under refrigeration, between 2° to 8°C (36° to 46°F).

Protect from freezing.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

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REFERENCES

  • ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice. Pittsburgh, PA: Oncology Nursing Society; 1999:32-41.
  • Recommendations for the safe handling of parenteral antineoplastic drugs. Washington, DC: Division of Safety, National Institutes of Health; 1983. US Dept of Health and Human Services, Public Health Service publication NIH 83-2621.
  • AMA Council on Scientific Affairs. Guidelines for handling parenteral antineoplastics. JAMA.1985; 253: 1590-1591.
  • National Study Commission on Cytotoxic Exposure. Recommendations for handling cytotoxic agents. 1987. Available from Louis P. Jeffrey, Chairman, National Study Commission on Cytotoxic Exposure. Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, MA 02115.
  • Clinical Oncological Society of Australia. Guidelines and recommendations for safe handling of antineoplastic agents. Med J Australia.1983; 1:426–428.
  • Jones RB, Frank R, Mass T. Safe handling of chemotherapeutic agents: a report from the Mount Sinai Medical Center. CA–A Cancer J for Clin.1983; 33:258–263.
  • American Society of Hospital Pharmacists, ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm.1990; 47:1033–1049.
  • Controlling Occupational Exposure to Hazardous Drugs. (OSHA Work-Practice Guidelines.). Am J Health-SystPharm.1996; 53:1669-1685.

Manufactured for:

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

Manufactured by:

Catalent Germany Eberbach GmbH

D-69412 Eberbach/Baden

Germany

REVISED: 4/2016

ETOP:R3

Toposar pharmaceutical active ingredients containing related brand and generic drugs:

infoActive ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Toposar available forms, composition, doses:

infoForm of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Toposar destination | category:

infoDestination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Toposar Anatomical Therapeutic Chemical codes:

infoA medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Toposar pharmaceutical companies:

infoPharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."ETOPOSIDE CAPSULE [MYLAN PHARMACEUTICALS INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."ETOPOSIDE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "etoposide". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Toposar?

Depending on the reaction of the Toposar after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Toposar not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Toposar addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sDrugs.com conducted a study on Toposar, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Toposar consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

Visitor reports

One visitor reported frequency of use

How often in a day do you take the medicine?
Are you taking the Toposar drug as prescribed by the doctor?

Few medications can be taken Twice in a day more than prescribed when the doctor's advice mentions the medicine can be taken according to frequency or severity of symptoms. Most times, be very careful and clear about the number of times you are taking the medication. The report of sDrugs.com website users about the frequency of taking the drug Toposar is mentioned below.
Visitors%
Twice in a day1
100.0%

One visitor reported age

Visitors%
46-601
100.0%

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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