Totect

Name: Totect

Totect Overview

Totect is a brand name medication included in a group of medications called Detoxifying agents for antineoplastic treatment. For more information about Totect see its generic Dexrazoxane

Totect Drug Class

Totect is part of the drug class:

  • Detoxifying agents for antineoplastic treatment

What is the most important information I should know about dexrazoxane?

You should not receive Totect if you are pregnant. It could harm the unborn baby. If possible before you receive Totect, tell your doctor if you are pregnant. It is not known whether Zinecard will harm an unborn baby.

You should not receive this medication if your chemotherapy does not include doxorubicin or a similar medication such as daunorubicin (Cerubidine), epirubicin (Ellence), idarubicin (Idamycin), or mitoxantrone (Novantrone).

Before you receive dexrazoxane, tell your doctor if you have liver or kidney disease, or if you are pregnant or breast-feeding.

Tell your doctor at once if you have serious side effects such as fever, chills, body aches, flu symptoms, easy bruising or bleeding, or sores your mouth or throat.

In an emergency situation it may not be possible before you are treated to tell your caregivers about your health conditions or if you are pregnant or breast feeding. Make sure any doctor caring for you afterward knows that you have received Totect.

What should I discuss with my health care provider before receiving dexrazoxane?

You should not receive Zinecard if your chemotherapy does not include doxorubicin or a similar medication such as:

  • daunorubicin (Cerubidine);

  • epirubicin (Ellence);

  • idarubicin (Idamycin); or

  • mitoxantrone (Novantrone);

If possible before you receive dexrazoxane, tell your doctor if you have:

  • liver disease;

  • kidney disease; or

  • if you are pregnant or breast-feeding.

Zinecard is rated as FDA pregnancy category C. It is not known whether Zinecard will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

Totect is rated as FDA pregnancy category D. Do not use Totect if you are pregnant. It could harm the unborn baby. If possible before you receive Zinecard, tell your doctor if you are pregnant.

It is not known whether dexrazoxane passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using dexrazoxane.

In an emergency situation, it may not be possible before you are treated with Totect to tell your caregivers if you are pregnant or breast feeding. Make sure any doctor caring for your pregnancy or your baby knows you have received this medication.

What should I avoid after receiving dexrazoxane?

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

Proper Use of dexrazoxane

This section provides information on the proper use of a number of products that contain dexrazoxane. It may not be specific to Totect. Please read with care.

A nurse or other trained health professional will give you this medicine. This medicine is given through a needle placed into one of your veins .

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

How is this medicine (Totect) best taken?

Use Totect as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

  • Call your doctor to find out what to do.

Consumer Information Use and Disclaimer

  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.
  • If your symptoms or health problems do not get better or if they become worse, call your doctor.
  • Do not share your drugs with others and do not take anyone else's drugs.
  • Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
  • Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
  • Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Totect, please talk with your doctor, nurse, pharmacist, or other health care provider.
  • If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Totect. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Totect.

Review Date: October 4, 2017

Totect Dosage and Administration

Vial contents must be mixed and diluted with 50 mL of 0.167 M sodium lactate injection solution before use.

Recommended Dose

Totect® should be given once daily for 3 consecutive days. Initiate the first infusion as soon as possible and within the first six hours after extravasation.

The individual dosage is based on calculation of the Body Surface Area (BSA) up to a maximum dose of 2000 mg (each on Day 1 and 2) and 1000 mg (Day 3), corresponding to a BSA of 2 m2.

The recommended dose is: Maximum daily dose:
Day one: 1000 mg/m2    2000 mg
Day two: 1000 mg/m2    2000 mg
Day three: 500 mg/m2    1000 mg

Dose Modifications

The Totect® dose should be reduced by 50% in patients with creatinine clearance values < 40 mL/min.

Directions for Mixing and Final Dilution

Read this entire section carefully before mixing and diluting.

Aseptic technique should be used during preparation.

Use caution when handling and preparing the reconstituted solution. The use of gloves is recommended. If Totect® powder or solutions contact the skin or mucosae, wash exposed area immediately and thoroughly with soap and water. Follow special handling and disposal procedures.1

Totect® should not be mixed or administered with any other drug during the infusion.

Preparation of Totect®

Step 1. Each vial of Totect® (dexrazoxane for injection) (500 mg) must first be mixed with 50 mL of 0.167M sodium lactate injection solution.

Dilution of sodium lactate injection to 0.167M is required before using it to reconstitute Totect®. Add 1.67 mL of 5 mEq/mL sodium lactate injection to 50 mL sterile water for injection to make 50 mL of 0.167M sodium lactate injection solution.

After reconstitution of Totect® with 50 mL of 0.167M sodium lactate injection solution, the resultant Totect® solution contains 10 mg/mL. This resultant solution should be further diluted within 2 hours. It contains no antibacterial preservative.

Step 2. Withdraw the recommended dose from the Totect® solution containing 10 mg/mL as prepared in Step 1 and further dilute into an infusion bag containing 1000 mL 0.9% Sodium Chloride. In order to obtain the required dose, more than one vial may be needed. Totect® must not be mixed with any other drugs.

The infusion bag should be used immediately after preparation. The product is stable for 4 hours from the time of preparation when stored below 25ºC (77ºF).

The solution of Totect® is slightly yellow.

Parenteral drug products should be inspected visually for particulate matter prior to administration, whenever solution and container permit. Solutions containing a precipitate should be discarded. Vials are for single use only. Unused solution should be discarded.

Administration

Totect® should not be mixed or administered with any other drug during the infusion. Administer as an intravenous infusion over 1 to 2 hours at room temperature and normal light conditions in a large caliber vein in an extremity/area other than the one affected by the extravasation. Cooling procedures such as ice packs, if used, should be removed from the extravasation area at least 15 minutes before Totect® administration in order to allow sufficient blood flow to the area of extravasation. Treatment on Day 2 and Day 3 should start at the same hour (+/- 3 hours) as on the first day.

Warnings and Precautions

Myelosuppression

Treatment with Totect® is associated with leukopenia, neutropenia, and thrombocytopenia. Hematological monitoring should be performed.

Use in Pregnancy

Pregnancy Category D

Totect® can cause fetal harm when administered to a pregnant woman. There is no adequate information about the use of Totect® in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. [see Use in Specific Populations (8.1)].

Adverse Reactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice.

In the clinical studies, Totect® was administered to patients also receiving chemotherapeutic agents for cancer, and the adverse reaction profile reflects the combination of Totect®, underlying disease, and already administered chemotherapy. The adverse reaction data reflect exposure to Totect® in 80 patients who received the first dose, 72 patients who received two doses, and 69 patients who received all three doses. Table 1 summarizes adverse reactions occurring with ≥ 5% frequency.

Table 1 Adverse Reactions Occurring at ≥ 5% Frequency
MedDRA System Organ Class (SOC) and Preferred term Study 1 and 2 Combined
(All causalities)
N=80 (%)
Total number of patients with at least one event 68 (85)
General disorders and administration site conditions 46 (58)
    Pyrexia 17 (21)
    Injection site pain/injection site discomfort 13 (16)
    Fatigue 10 (13)
    Edema peripheral 8 (10)
    Injection site phlebitis 5 (6)
Gastrointestinal disorders 44 (55)
    Nausea 34 (43)
    Vomiting 15 (19)
    Diarrhea 9 (11)
    Abdominal pain 5 (6)
    Constipation 5 (6)
Infections and infestations 24 (30)
    Postoperative infection 13 (16)
Nervous system disorders 19 (24)
    Dizziness 9 (11)
    Headache 5 (6)
Skin and subcutaneous disorders 14 (18)
    Alopecia 11 (14)
Respiratory, thoracic and mediastinal disorders 13 (16)
    Dyspnea 6 (8)
    Pneumonia
    Cough
5 (6)
4 (5)
Vascular disorders 12 (15)
Blood and lymphatic system disorders 11 (14)
    Anemia 5 (6)
Psychiatric disorders 11 (14)
    Depression
    Insomnia
6 (8)
4 (5)
Musculoskeletal and connective tissue disorders 10 (13)
Metabolism and nutrition disorders
    Anorexia
8 (10)
4 (5)
Cardiac disorders 4 (5)

Neutropenia and febrile neutropenia each occurred in 2.5% of patients.

Table 2 summarizes laboratory adverse events from studies 1 and 2.

Table 2: Laboratory Adverse Reactions
CTCAE version 3
Term
CTC grade 3 CTC grade 4 CTC grade 2 to 4
N (%) N (%) N (%)
Hematologic:
Decreased hemoglobin 2 (3) 0 34 (43)
Decreased WBC 20 (25) 16 (20) 58 (73)
Decreased neutrophils 17 (22) 19 (24) 48 (61)
Decreased platelets 17 (21) 0 21 (26)
Hepatic:
Increased bilirubin 1 (2) 0 6 (11)
Increased AST 1 (1) 1 (1) 21 (28)
Increased ALT 1 (1) 4 (5) 17 (22)
Increased alkaline phosphatase 0 0 3 (4)
Increased LDH 0 0 1 (5)
Metabolic:
Increased creatinine 1 (2) 1 (2) 8 (14)
Decreased sodium 4 (5) 1 (1) 5 (6)
Increased calcium total 1 (2) 1 (2) 4 (7)
(web3)