Vexdo 20/Vexdo 80

Vexdo 20/Vexdo 80

docetaxel

Manufacturer:

Vexxa Lifesciences

Distributor:

VE Pharma
Full Prescribing Info
Contents
Docetaxel.
Description
Vexdo 20: (Docetaxel Injection 20 mg/0.5 mL) Concentrate: Each vial contains: Docetaxel Trihydrate eq. to Docetaxel 20 mg, Polysorbate 80 USP q.s to 0.5 mL.
Diluent (Solvent for Injection 0.5 mL/1.5 mL): Each vial contains: Alcohol (95% v/v) USP 13% w/v (Absolute Alcohol content 15.25% v/v), Water for Injection USP q.s. to 1.5 mL.
Vexdo 80: (Docetaxel Injection 80 mg/2.0 mL (40 mg/mL)) Concentrate: Each single dose vial contains: Docetaxel Trihydrate eq. to Docetaxel 80 mg Polysorbate 80 USP q.s to 2.0 mL.
Diluent (Solvent for Injection 2.0 mL/6.0 mL): Each vial contains: Alcohol (95% v/v) USP 13% w/v (Absolute Alcohol content 15.25% v/v), Water for Injection USP q.s. to 6.0 mL.
Docetaxel is a cancer medication that interferes with the growth and spread of cancer cells in the body. Docetaxel is used to treat breast cancer, lung cancer, prostate cancer, stomach cancer, and head/neck cancer.
Chemical name: 1,7β,10β-Trihydroxy-9-oxo-5β,20-epoxytax-11-ene-2α,4,13α-triyl 4-acetate 2-benzoate13-[(2R,3S)-3-[[(1,1-dimethylethoxy) carbonyl]amino]-2-hydroxy-3-phenylpropanoate].
Action
Pharmacological Classification: Antineoplastic.
Pharmacology: Docetaxel is an antineoplastic agent acting at the microtubules. Docetaxel enhances polymerization of the tubulin into stable microtubules and inhibits their depolymerisation. This induces the formation of stable microtubules bundles leading to cell death.
Pharmacokinetics: On intravenous dosage docetaxel is rapidly distributed to body tissues. Docetaxel is more than 95% bound to plasma proteins. It is extensively metabolised via hepatic cytochrome P450 isoenzyme CYP3A4 and excreted chiefly in the faeces as metabolites. Only about 6% of a dose is excreted in urine. The terminal elimination half-life is about 11 hours. Clearance is reduced in hepatic impairment.
Indications/Uses
Vexdo (Docetaxel Injection) is a microtubule inhibitor indicated for: Breast Cancer (BC): Single agent for locally advanced or metastatic BC after chemotherapy failure; and with doxorubicin and cyclophosphamide as adjuvant treatment of operable node positive BC.
Non-Small Cell Lung Cancer (NSCLC): Single agent for locally advanced or metastatic NSCLC after platinum therapy failure; and with cisplatin for unresectable, locally advanced of metastatic untreated NSCLC.
Hormone Refractory Prostate Cancer (HRPC): With prednisone in androgen independent (Hormone Refractory) metastatic prostate cancer.
Gastric Adenocarcinoma (GC): With cisplatin and fluorouracil for untreated, advanced GC, including the gastroesophageal junction.
Squamous Cell Carcinomas of the Head and Neck Cancer (SCCHN): with cisplatin and fluorouracil for induction treatment of locally advanced SCCHN.
Dosage/Direction for Use
Breast Cancer (BC): Docetaxel is given by intravenous infusion in glucose 5% or sodium chloride 0.9% at a concentration not exceeding 0.74 mg/mL. Infusion is normally over 1 hour. Premedication with an oral corticosteroid, such as dexamethasone 16 mg daily, for 3 days starting 1 day before docetaxel is recommended with many regimens. The licensed dose for docetaxel as a single agent in the treatment of breast cancer after failure of previous chemotherapy is 60 to 100 mg/m2 once every 3 weeks. A dose of 75 mg/m2 once every 3 weeks is given in combination therapy with doxorubicin, or capecitabine, or when used as adjuvant therapy with doxorubicin and cyclophosphamide. When used with trastuzumab, docetaxel is given at a dose of 100 mg/m2 once every 3 weeks.
Non-Small Cell Lung Cancer (NSCLC): The dose for non-small cell lung cancer is 75 mg/m2 once every 3 weeks, for both first-line combination therapy and monotherapy after failure of previous chemotherapy.
Gastro Adenocarcinoma (GC): For gastric adenocarcinoma docetaxel 75 mg/m2 is given before cisplatin and fluorouracil; treatment is repeated every 3 weeks.
Squamous Cell Carcinomas of the Head and Neck Cancer (SCCHN): In the induction treatment of head and neck cancer, the recommended dose of docetaxel is 75 mg/m2, given before cisplatin and fluorouracil; treatment is given every 3 weeks for 3 cycles, followed by chemoradiotherapy, or for 4 cycles when followed by radiotherapy alone.
Hormone Refractory Prostate Cancer (HRPC): For prostate cancer, the dose of docetaxel is 75 mg/m2 once every 3 weeks, with prednisone or prednisolone 5 mg orally twice daily given continuously.
The use of prednisone or prednisolone reduces the need for a premedication corticosteroid; dexamethasone 8 mg may be given at 12 hours, 3 hours, and 1 hour before docetaxel. Regular blood counts are required, and dosage in subsequent courses should be reduced in patients who experience severe or febrile neutropenia, or severe cutaneous reactions or peripheral neuropathy. The dose of docetaxel should be reduced in hepatic impairment.
Administration: Docetaxel has been investigated as a low dose weekly infusion, in patient groups such as the elderly, those with poor performance status, or refractory disease. Weekly doses of 30 to 40 mg/m2 are considered to be of similar efficacy to the standard three-weekly dosage regimen. A pharmacokinetic study in 20 elderly patients suggested that a suitable starting dose might be 26 mg/m2, increased provided there was no toxicity.
Administration in hepatic impairment: The doses of docetaxel monotherapy should be reduced from 100 mg/m2 to 75 mg/m2 in mild to moderate hepatic impairment, defined as alanine aminotransferase (ALT/SGPT) and/or aspartate aminotransferase (AST/SGOT) more than 1.5 times the upper limit of normal (ULN), and alkaline phosphatase more than 2.5 times the ULN. Hepatic function should be monitored; use should be avoided if possible in severe hepatic impairment. The use of docetaxel in patients with bilirubin above ULN, or in those with mild to moderate hepatic impairment.
Overdosage
There is no known antidote for Docetaxel overdose. The known complication of overdose includes neutropenia, cutaneous reactions and sensory neuropathy. The patient should be kept in specialized unit and vital functions should be closely monitored in such case of overdose and myalgias, hypotension and injection site reactions.
Contraindications
Docetaxel should not be used in patients hypersensitive to polysorbate 80, which is contained in the formulation. Patients with hepatic impairment show increased sensitivity to toxic effects of docetaxel, and should be given the drug with great care and in reduced doses, if at all.
Hypersensitivity: However, hypersensitivity reactions have also occurred with docetaxel and taxane cross-reactivity has been reported.
Tumour lysis syndrome: Fatal cases of tumour lysis syndrome have been reported after the second-line use of docetaxel.
Special Precautions
Docetaxel should be administered under supervision of a physician experienced in the use of cancer chemotherapeutic agents since significant hypersensitivity reactions may occur, appropriate management of complications is possible only when adequate diagnostic and treatment facilities are readily available. During the infusion, it is recommended that vital functions should be closely monitored. In order to reduce the fluid retention all the patients should be premedicated with oral corticosteroids like Dexamethasone 16 mg per day for 4-5 days beginning 1 day prior to Docetaxel administration.
Patients should be treated with Docetaxel only when baseline neutrophil count is >1500/mm3. Frequent monitoring of complete blood count should be performed regularly during Docetaxel therapy. The subsequent dose of Docetaxel should be reduced in case of Grade IV neutropenia (neutrophil Count <500/mm3) lasting for 7 days or more.
Hypersensitivity reaction (HSR) may occur within a few minutes following the initiation of the infusion of Docetaxel. Minor HSR may manifest as mild flushing or localized skin reactions however interruption of therapy is not required in such cases.
Severe HSRs such as hypotension (reduction of blood pressure by more than 20 mm Hg) or bronchospasm or generalized rashes require immediate cessation of infusion and aggressive symptomatic therapy. Patients who have developed severe HSRs should not be rechallenged with Docetaxel.
Peripheral neuropathy may be observed in a few patients' during Docetaxel therapy. Subsequent dose reduction is suggested in case of peripheral neuropathy.
Safety of Docetaxel has not been established in children; hence a cautious use is suggested utilizing risk vs. benefit ratio as Safety of Docetaxel has not been established in pregnancy and lactation, the women with child bearing age should avoid pregnancy.
Skin reactions such as localized skin erythema of the extremities (palm of the hand and sole of the feet) with oedema followed by desquamation have been reported with Docetaxel therapy. This type of toxicity can lead to interruption and discontinuation of therapy.
Use In Pregnancy & Lactation
A cautious use is suggested utilizing risk vs. benefit ratio as Safety of Docetaxel has not been established in pregnancy and lactation, the women with child bearing age should avoid pregnancy.
Adverse Reactions
The most common adverse reactions across all Vexdo (Docetaxel Injection) indications are infections, neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, diarrhea, vomiting, mucositis, alopecia, skin reactions, and myalgia.
Neutropenia, anaemia and skin reactions are common with docetaxel and may be severe. Fluid retention, resulting in oedema, ascites, pleural and pericardial effusion, and weight gain, is also common, and may be cumulative; premedication with a corticosteroid can reduce fluid retention as well as the severity of hypersensitivity reactions. Asthenia and fatigue have also been reported. Rare cases of ototoxicity, hearing impairment or loss have occurred.
Very rare cases of acute myeloid leukaemia and myelodysplastic syndrome have been reported with combination chemotherapy regimens containing docetaxel; haematological follow-up may be required.
Effects on the eyes: Excessive tear formation (epiphora) severe enough to interfere with reading and driving has been reported in patients given docetaxel. Canalicular stenosis has been described as the mechanism for this effect, and docetaxel has been measured in tear fluid suggesting that irritation of the ocular surface and fibrosis of the tear drainage ducts may be caused by direct contact with docetaxel. Epiphora and canalicular stenosis are more severe and occur more frequently in patients who receive weekly docetaxel than in those who receive the drug every 3 weeks. The mean cumulative dose of docetaxel was found to be higher in those patients who developed stenosis. Management of this adverse effect includes probing and irrigation of the lachrymal ducts and canalicular silicone tubing placement, or surgery followed by tube placement. The condition is generally reversible and tubing can be removed 4 to 6 weeks after stopping docetaxel therapy. The use of topical tobramycin and dexamethasone on a tapering regimen can eliminate the need for silicone intubation or surgery in some patients.
Very rare cases of transient visual disturbances such as flashing lights and scotomata have occurred during docetaxel infusion, and in association with hypersensitivity reactions. These were reversible upon stopping the infusion. For reference to a report of glaucoma possibly related to docetaxel.
Effects on the gastrointestinal tract: Ischaemic colitis has occurred in patients treated with docetaxel. Some patients also received vinorelbine, which may have exacerbated this complication.
Effects on the heart: For comment on the increased risk of heart failure when docetaxel is given with trastuzumab and after anthracyclines, see under Interactions.
Effects on the musculoskeletal system: For reference to cases of taxane-induced arthralgia and myalgia successfully treated with gabapentin.
Effects on the skin and nails: Palmar-plantar erythrodysesthesia syndrome has been reported with the use of docetaxel. For reference to the use of vitamin E to alleviate palmar-plantar erythrodysesthesia syndrome caused by docetaxel and capecitabine. Cases of radiation recall dermatitis associated with docetaxel have also been reported. There is a further report of recall dermatitis at sites previously treated with a laser. A hyperpigmented eruption developed in a patient at the site of docetaxel injection after insufficient venous flushing; no eruption occurred after a second infusion with abundant venous flushing. Licensed drug information states that very rare cases of bullous eruption such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported with docetaxel, but that other factors may have contributed to the development of these reactions. For further reference to reports of scleroderma and adverse effects on the nails after the use of docetaxel.
In a multicentre study, patients given docetaxel wore a frozen glove on the right hand, leaving the left hand unprotected to serve as a control. The use of the glove significantly reduced skin and nail toxicity.
Caution For Usage
Preparation for the Intravenous Administration: A) Preparation of Docetaxel premix solution: Take vials of Docetaxel should be allowed to stand for five minutes to bring to room temperature. The vial is then appropriately diluted aseptically with the solvent (provided) withdrawn into a syringe to obtain an initial Docetaxel concentration of 10 mg/ml. Shake the vial for 15 seconds by manual rotation and allow to stand for five minutes at room temperature. The solution thus obtained should be clear and homogenous.
B) Preparation of the infusion solution: The required amount of Docetaxel premix solution is withdrawn aseptically with a calibrated syringe and the premix volume is injected into an infusion bag or bottle of either 0.9% Sodium Chloride injection or 5% Dextrose Injection to produce a final Docetaxel concentration of 0.3 to 0.9 mg/ml. The concentration of Docetaxel in final solution should never exceed 0.9 mg/ml. The infusion solution should then be thoroughly mixed by manual rotation.
Docetaxel infusion solution is administered as one hour intravenous infusion under room temperature and normal lighting conditions.
Stability: Vexdo (Docetaxel Injection) is stable for 4 hr at 2°C to 25°C after constitution with Diluent (Solvent for Injection). Final dilution of Vexdo (Docetaxel Injection) for infusion (in either 0.9% Sodium Chloride solution or 5% Dextrose solution) should be used within 4 hours.
Storage
Store at temperatures not exceeding 30°C. Protect from light.
Shelf Life: Two Years from the date of manufacturing.
ATC Classification
L01CD02 - docetaxel ; Belongs to the class of plant alkaloids and other natural products, taxanes. Used in the treatment of cancer.
Presentation/Packing
Vexdo 20: Soln for inj (clear yellow to brownish yellow coloured viscous) 20 mg/0.5 mL (5 mL vial + 1.5 mL diluent) x 1's.
Vexdo 80: Soln for inj (clear yellow to brownish yellow coloured viscous) 80 mg/2 mL (40 mg/mL) (10 mL vial + 6 mL diluent) x 1's.
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