Docetaxel Alcohol-free Main Life

Docetaxel Alcohol-free Main Life

docetaxel

Manufacturer:

Nipro Pharma

Distributor:

Yu Chun
/
Main Life
Full Prescribing Info
Contents
Docetaxel.
Description
Description and Product description: (See Table 1.)

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Pharmaceutical matter: (See Table 2.)

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Non proprietary name: Docetaxel
Chemical name: (1S,2S,3R,4S,5R,7S,8S,10R,13S)-4-Acetoxy-2-benzoyloxy-5,20-epoxy-1,7,10-trihydroxy-9-oxotax-11-en-13-yl(2R,3S)-3-(1,1-dimethylethyl)oxycarbonylamino-2-hydroxy-3-phenylpropanoate
Molecular formula: C43H53NO14
Molecular weight: 807.88
It occurs as a white powder.
It is freely soluble in N,N-dimethylformamide and in ethanol (99.5), soluble in methanol, slightly soluble in acetonitrile, and practically insoluble in water.
Indications/Uses
Breast cancer, non-small cell lung cancer, gastric cancer, head and neck cancer. Prostate cancer.
Precautions for Indications: As for prostate cancer, this drug should be administered to patients who have undergone surgical or medical castration and in whom progression or recurrence has been observed.
Dosage/Direction for Use
(See Table 3.)

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Precautions for Dosage and Administration: At administration of this drug, be very cautious about especially change in neutrophil count, dose limiting factor of this drug, and if the neutrophil count of the day of administration is less than 2,000/mm3, the administration should be extended.
Pay attention that the bone-marrow suppression may be enhanced with increased dose of this drug. (See Precautions and Adverse Reactions.)
At administration of this drug, draw up the necessary amount into syringe, immediately mix with 250 mL or 500 mL of physiological saline or 5% glucose solution, and intravenously infuse over 1 hour or more. (See Cautions for Usage.)
Overdosage
Antidote for overdosage of this drug is not known. Main complications expected to occur at overdosage include bone-marrow suppression, peripheral neurotoxicity, and mucositis. If the overdosage occurs, control the patients under special facilities and closely monitor vital signs, etc.
Contraindications
Docetaxel is contraindicated in the following patients: Patients with serious bone-marrow suppression [Severe infection, etc. may concomitantly occur and it may become life threatening].
Patients with concomitant infection [Infection may worsen and it may become life threatening].
Patients with fever suspected infection [Infection may worsen and it may become life threatening].
Patients with a history of serious hypersensitivity to this drug or preparations containing polysorbate 80. [This drug contains polysorbate 80.]
Patients who are or may be pregnant (see Use in Pregnancy & Lactation).
Warnings
Dose limiting factor (DLF) of this drug is neutropenia. With the use of this drug, serious bone-marrow suppression (especially neutropenia), serious adverse reactions such as severe infections, and death cases whose causality with this drug cannot be ruled out have been observed. Therefore, cancer chemotherapy including this drug should be performed at medical facilities that can deal with emergency situation under physicians with sufficient knowledge and experience of cancer chemotherapy in only patients who were judged to be proper for the administration of this drug. In addition, patients who are indicated to this drug should be selected carefully, such as not administering this drug to the following patients: Patients with serious bone-marrow suppression; Patients with concomitant infection; Patients with fever suspected infection.
At starting treatment, give adequate explanation about efficacy and risk to patients or his/her family and receive consent before administration. Read the package insert well before using this drug.
Special Precautions
Careful Administration (Docetaxel should be administrated with care in the following patients.): Patients with bone-marrow suppression [Bone-marrow suppression may worsen and severe infection, etc. may concomitantly occur].
Patients with interstitial pneumonia or pulmonary fibrosis [Symptoms may worsen].
Patients with liver disorder [Blood concentration of this drug may increase and adverse reactions may be enhanced.] (see Other Precautions as follows).
Patients with renal disorder [Renal disorder may worsen].
Patients with edema [Edema may worsen].
Patients who may become pregnant (see Important Precautions as follows).
Important Precautions: Since serious bone-marrow suppression occur frequently, be cautious about the following: (1) Adequate observation of the patient's condition such as frequent laboratory testing (blood test, etc.) should be performed. If any abnormality is observed, take proper measures such as dose reduction or withholding.
(2) Pay extra attention to the onset of infection and check the presence or absence of symptoms such as neutropenia, elevated CRP, and fever. If the infection occurs or worsens, immediately take proper measures such as administration of antibiotics (In a clinical study in Japanese patients conducted by another company, the incidence of infection was higher in patients with prostate cancer [70 mg/m2] comparing with patients with other types of cancer [70 mg/m2]).
Since efficacy on focus of brain metastasis has not yet been established, consider other treatments regarding focus of brain metastasis.
Since serious symptoms of irritation due to this drug may appear, patients should be adequately observed especially at the first and second administration of this drug. Since symptoms of irritation may appear within few minutes after starting administration of this drug, patients should be adequately observed for 1 hour after starting administration of this drug with frequent monitoring of vital signs (such as blood pressure and pulse rate), etc. If serious symptoms of irritation (such as dyspnea, bronchospasm, decreased blood pressure, chest pressure sensation, and rash) should be observed, immediately stop administration of this drug and take appropriate measures. This drug should not be re-administered to patients who have developed serious symptoms of irritation. (See Other Precautions as follows and Clinically significant adverse reactions under Adverse Reactions.)
Adequate observation about cardiocirculatory system should be performed (Occasionally, cardiac failure, decreased blood pressure, arrhythmia, palpitation, etc. may occur).
Since embryotoxicity (such as embryonic resorption, fetal death, growth retardation), and findings indicating teratogenicity were observed in animal studies (rats), be cautious about the following: (1) Confirm before starting administration that the patient is not pregnant.
(2) As a general rule, this drug should not be administered to patients who may become pregnant. If this drug is administered by necessity, give sufficient explanation that this drug can cause obstruction in maintenance of pregnancy and development of fetus and instruct to use contraception without fail.
(3) If pregnancy is confirmed or suspected while the patients are on this drug, discontinue administration immediately.
Testicular toxicity has been observed in animal studies (mice, rats, dogs). If this drug must be administered to patients of reproductive age, consider about the effects on gonad.
Other Precautions: Premedication in other countries: In Europe and the United States, where the daily maximum dose of docetaxel is 100mg/m2, incidence and seriousness of edema are higher. Therefore, premedication with adrenal corticosteroid for relieving edema and symptoms of irritation is performed. As a premedication, it is considered to be desirable to administer medicine such as dexamethasone (16 mg/day, 8 mg twice daily) orally as a single agent for 3 days from 1 day before starting docetaxel. However, deaths due to serious hypersensitivity (anaphylactic shock) in patients with premedication have been reported.
In addition, there is the following report regarding edema: When docetaxel 100mg/m2 was intravenously infused at a three-week interval, incidence of edema increased when cumulative dose (median) of 818.9mg/m2 or more was administered in previously mentioned patients with premedication, and 489.7mg/m2 or more in patients without premedication.
After discontinuation of docetaxel, edema gradually improves. Edema develops from lower extremities and it may become generalized with increase of body weight by 3 kg or more, but it is not accompanied by acute oliguria or hypotension. Dehydration and pulmonary edema have been infrequently reported.
Administration to patients with abnormal hepatic function in other countries: In other countries, when docetaxel 100mg/m2 was intravenously infused at a three-week interval, enhancement and worsening of serious adverse reactions were observed when docetaxel was administered in patients with increased transaminase (more the 1.5 times of upper limit of normal) with increased blood alkaline phosphatase level (more the 2.5 times of upper limit of normal), and in patients with increased blood bilirubin (exceeding upper limit of normal). Reported adverse reactions include grade 4 neutropenia, febrile neutropenia, infection, serious thrombocytopenia, serious stomatitis, and skin symptoms such as peeling of skin. It was warned that risk of treatment-related death would increase.
Occurrence of acute leukemia and myelodysplastic syndrome (MDS) were reported in patients who concomitantly received this drug and other antineoplastics or radiation therapy.
Among mutagenicity tests, positive results in both of chromosomal aberration assay using cultivated cell line from Chinese hamster ovary (CHO-K1) and micronucleus test using mice have been obtained.
In a phase II clinical study in Japan conducted by another company, with the administration method of 35 mg/m2 once weekly (35 mg/m2 once daily, administered on Days 1, 8, 15, repeated every 4 week) against non-small cell lung cancer, interstitial pneumonia was noted in 6 patients among 48 patients. (Unapproved dosage and administration).
**In the overseas clinical trial of postoperative adjuvant chemotherapy for breast cancer patients conducted by another company, cases of continuous hair loss in patients administrated with the combination of docetaxel and other antineoplastic agent were reported at the end of observation period (incidence rate 3.9%(29/744), median of observation period 96 months).
Use in the Elderly: Be cautious about adverse reactions and pay attention to dosage interval and dose. If any adverse reactions occur, take proper measures such as withholding or extending dosage interval. [Elderly patients generally have reduced physiological function.]
Use in Children: The safety of this drug in low birth weight infants, neonates, infants, toddlers, and children has not yet been established (no clinical experience).
Use In Pregnancy & Lactation
Do not administer this drug to patients who are or may be pregnant. [Findings indicating embryofetal lethality, retarded growth and developmental of fetus and litters, and teratogenicity were observed in animal studies (rats).]
When administrating to nursing women, breast feeding should be discontinued. [Excretion in breast milk in animal studies has been reported.]
Adverse Reactions
Investigation to identify the incidence of adverse reactions regarding this drug has not been performed.
Clinically significant adverse reactions (incidence unknown): Bone-marrow suppression: Pancytopenia, leukocytopenia, neutropenia (including febrile neutropenia), reduction in hemoglobin, thrombocytopenia, etc. may occur. Conduct blood test adequately and if any abnormality is observed, take proper measures such as extending dosage interval, dose reduction or withholding. In addition, consider proper use of G-CSF preparation at administration of this drug.
Shock symptom, anaphylaxis: Shock symptom and anaphylaxis such as dyspnea, bronchospasm, decreased blood pressure, chest pressure sensation, and rash may occur. Observe closely and if related signs are noted, discontinue this drug and take proper measures.
Jaundice, hepatic failure, hepatic function disorder: Since serious hepatic impairment such as jaundice, hepatic failure and marked elevation in AST (GOT), ALT (GPT) and Al-P may occur, closely observe by paying attention to the level of liver function test and if any abnormality is observed, take proper measures such as discontinuation.
Acute renal failure: Since serious renal impairment such as acute renal failure may occur, closely observe by paying attention to the level of kidney function test and if any abnormality is observed, take proper measures such as discontinuation.
Interstitial pneumonia, pulmonary fibrosis: Interstitial pneumonia and pulmonary fibrosis may occur (see Precautions). Similar clinical symptoms (radiation pneumonitis) may occur in patients receiving concomitant radiation therapy (see Interactions). Observe closely and if any abnormality is observed, take proper measures such as discontinuation.
Cardiac failure: Since cardiac failure may occur, observe closely and if any abnormality is observed, take proper measures such as discontinuation.
Disseminated intravascular coagulation (DIC): Since disseminated intravascular coagulation (DIC) may occur, blood tests including platelet count, serum FDP level, and plasma fibrinogen concentration should be conducted as needed. Observe closely and if any abnormality is observed, take proper measures such as discontinuation.
Intestinal perforation, gastrointestinal hemorrhage, ischemic colitis, colitis: Intestinal perforation, gastrointestinal hemorrhage, ischemic colitis and colitis may occur. If symptoms such as abdominal pain, hematemesis, melena, diarrhea, etc. occur, take proper measures such as discontinuation.
Ileus: Since ileus may occur, observe closely and if any abnormality is observed, take proper measures such as discontinuation.
Acute respiratory distress syndrome: Acute respiratory distress syndrome may occur. If respiratory impairment is noted, observe closely and take proper measures such as discontinuation.
Acute pancreatitis: Since acute pancreatitis may occur, observe closely and if any abnormality is observed in the levels of serum amylase, etc., take proper measures such as discontinuation.
Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), erythema multiforme: Bullous rash and exudative rash such as Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), erythema multiforme may occur. Observe closely and if any abnormality is observed, take proper measures such as discontinuation.
Cardiac tamponade, pulmonary edema, edema and fluid retention: Serious edema and fluid retention such as cardiac tamponade, pulmonary edema and pleural effusion and ascites requiring emergency drainage have been reported. (See Precautions.)
Cardiac infarction, venous thromboembolism: Cardiac infarction and venous thromboembolism have been reported.
Infection: Infection such as sepsis and pneumonia has been reported. If any abnormality is observed, take proper measures immediately. (See Precautions.)
Syndrome of inappropriate antidiuretic hormone secretion (SIADH): Syndrome of inappropriate antidiuretic hormone secretion (SIADH) may occur. If symptoms such as hyponatremia with a low plasma osmolality, increase in urine sodium excretion, spasm, and disturbed consciousness occur, discontinue the administration and take proper measures such as restriction of fluid intake.
Other significant adverse reactions such as serious mucositis including stomatitis, vasculitis, peripheral nerve disorder, peripheral motor disorder including a feeling of weakness in four extremities, and radiation recall phenomenon have been reported.
Other adverse reactions: If the following adverse reactions are observed, take proper measures such as dose reduction, withholding, or discontinuation. (See Table 4.)

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Drug Interactions
This drug is metabolized mainly by CYP3A4, a drug-metabolizing enzyme. Therefore, if the medical agent that affects the activity of this enzyme is concomitantly used, administer with caution.
Precautions for Coadministration (Docetaxel should be administered with care when coadministered with the following drugs.): (See Table 5.)

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Caution For Usage
At preparation: Since the concentration of drug, etc. are different between this drug and other docetaxel preparation, do not use at the same time.
Since this drug is viscous, using of 18G injection needle is preferable for drawing it up into syringe.
*After injecting this drug to infusion solution (250ml or 500ml, physiological saline or 5% glucose solution), continue mixing procedure gently until complete dissolving and mixing can be confirmed visually. The recommended final concentration is 0.3-0.74 mg/mL.
After mixing with infusion solution (250ml or 500ml, physiological saline or 5% glucose solution), use it at once. However the chemical and physical stability of the infusion solution has been demonstrated for 24 hours when stored at room temperature (below 25°C), in non-PVC bag.
Do not co-infuse with other agents.
If this drug has contact with skin, immediately wash away with soap and plenty of running water. In addition, if it has contact with mucosa, immediately wash away with plenty of running water.
At administration: Be sure to administer intravenously over 1 hour or more. Do not administer this drug subcutaneously or intramuscularly.
At intravenous injection, leaking of the medicinal solution from the vessel may cause induration and necrosis at injection sites. Administer the medicinal solution in a way that it will not leak from the vessel.
Precautions for Handling: Stability test: Docetaxel Concentrate for Solution for Infusion 20 mg/1 mL: As a result of long term storage test using final container product (25°C, relative humidity 60%, for 3 years), appearance and contents were within the specified range. Thus Docetaxel Concentrate for Solution for Infusion 20 mg/1 mL was confirmed to be stable for 3 years under the usual market circulation.
Docetaxel Concentrate for Solution for Infusion 80 mg/4 mL: As a result of long term storage test using final container product (25°C, relative humidity 60%, for 3 years), appearance and contents were within the specified range. Thus, Docetaxel Concentrate for Solution for Infusion 80 mg/4 mL was confirmed to be stable for 3 years under the usual market circulation.
Storage
Store away from light, below 25°C (After opening the package, store the vial in the box).
ATC Classification
L01CD02 - docetaxel ; Belongs to the class of plant alkaloids and other natural products, taxanes. Used in the treatment of cancer.
Presentation/Packing
Conc for soln for infusion (vial) (pale yellow to brownish yellow clear liquid) 20 mg/mL x 1's. 80 mg/4 mL x 1's.
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