Paclitaxel-Teva, 6 mg/ml 50 ml

Indications

Ovarian cancer

Breast Cancer

Active ingredient

Composition

How to take, the dosage

Paclitaxel is given intravenously as an infusion.

In order to avoid severe hypersensitivity reactions, all patients should be premedicated with glucocorticosteroids, H1- and H2-histamine receptor blockers, such as:

or

Patients with solid tumors should not receive repeated courses of Paclitaxel-Teva until a neutrophil count of 1500/μL (1000/μL in patients with AIDS-related Kaposi sarcoma) and a platelet count of 100,000/μL (75,000/μL in patients with AIDS-related Kaposi sarcoma) are achieved. For patients who developed severe neutropenia (neutrophil count was less than 500/μL for more than one week) or with severe peripheral neuropathy in subsequent courses of treatment with Paclitaxel-Teva the dose should be reduced by 20% (by 25% in patients with AIDS-related Kaposi sarcoma). Neurotoxicity and neutropenia are dose-dependent.

Ovarian Cancer

First-line therapy

Platinum drug

or

Second-line therapy (monotherapy)

once every 3 weeks: 175 mg/m2 dose as a 3-hour intravenous infusion.

Breast Cancer

Adjuvant therapy is given after standard combination treatment. Paclitaxel-Teva is administered at a dose of 175 mg/m2 as a 3-hour intravenous infusion. A total of 4 courses of therapy 3 weeks apart is recommended.

First-line therapy

Monotherapy:dose of 175 mg/m2 as a 3-hour intravenous infusion every 3 weeks.

Combination therapy:

Second-line therapy

Dose of 175 mg/m2 as a 3-hour intravenous infusion every 3 weeks.

Non-small cell lung cancer

Combination therapy:

or

Monotherapy:dose of 175 mg/m2-225 mg/m2 as a 3-hour intravenous infusion every 3 weeks.

Sarcoma of Kaposi due to AIDS

.Second-line therapy

Dose of 135mg/m2 As a 3-hour intravenous infusion every 3 weeks, or a dose of 100 mg/m2 intravenous drip for 3 hours every 2 weeks (45-50 mg/m2 per week). Depending on the level of immunosuppression in patients with advanced AIDS, the following measures are recommended:

Interaction

Cisplatin

In the recommended regimen of paclitaxel as first-line chemotherapy for ovarian cancer, the drug should be administered before cisplatin. In this case, the safety profile of paclitaxel does not differ from that of monotherapy. Myelosuppression is greater when paclitaxel is administered after cisplatin and paclitaxel clearance is 20% lower than when cisplatin is administered after paclitaxel.

Doxorubicin

The use of paclitaxel in combination with doxorubicin may increase the serum concentration of doxorubicin and its active metabolite, doxorubicinol. Side effects such as neutropenia and stomatitis are more pronounced when paclitaxel is used before doxorubicin is administered and when a longer than recommended infusion is given.

Substrates, inducers and inhibitors of isoenzymes CYP2C8 and CYP3A4

Paclitaxel is metabolized with the participation of CYP2C8 and CYP3A4 isoenzymes, so caution should be exercised when using paclitaxel against treatment with substrates (e.g., midazolam, buspirone, felodipine, lovastatin, eletripan, sildenafil, simvastatin triazolam, repaglinide, and rosiglitazone), inducers (e.g., rifampicin, carbamazepine, phenytoin, efavirenz, nevirapine) or inhibitors (e.g., erythromycin, fluoxetine, gemfibrozil, ketoconazole, ritonavir, indinavir, nelfinavir) of these isozymes.

The results of studies of paclitaxel pharmacokinetics in patients with Kaposi’s sarcoma who received concomitant therapy with several drugs indicate a significant decrease in systemic clearance of paclitaxel when nelfinavir and ritonavir, but not indinavir are used simultaneously. There is not enough information on the interaction of paclitaxel with other protease inhibitors. Therefore, paclitaxel should be used with caution in patients receiving concomitant therapy with protease inhibitors.

Other interactions

An increased risk of fatal systemic vaccine disease is possible when coadministered with live vaccines. The use of live vaccines in immunosuppressed patients is not recommended.

Special Instructions

Paclitaxel-Teva should be administered under the supervision of a physician experienced in the use of antitumor chemotherapeutic agents.

Synopsis

Contraindications

Cautions

Thrombocytopenia (less than 100000/µl of blood), hepatic insufficiency, acute infectious diseases (including shingles, varicella, herpes), severe coronary heart disease, myocardial infarction (history), arrhythmias.

Side effects

Side effects of paclitaxel generally do not differ in frequency and severity in the treatment of ovarian cancer, breast cancer, non-small cell lung cancer or Kaposi’s sarcoma. However, in patients with AIDS-related Kaposi’s sarcoma, infections (including opportunistic infections), depressed hematopoiesis, and febrile neutropenia are more frequently and more severe than usual when using the drug.

Side effects during monotherapy:

The frequency of side effects is given according to the following scale: very common (≥10), common (≥100 but ˂ 1/10), infrequent (≥1000 but ˂ 1/100), rare (≥10000 but ˂ 1/1000), very rare (˂ 10000), frequency unknown (cannot be estimated with available data).

Hematopoietic Organs: very common – myelosuppression, neutropenia, anemia, thrombocytopenia, leukopenia, fever, bleeding; rare* – febrile neutropenia; very rarely* – acute myeloid leukemia, myelodysplastic syndrome; frequency unknown – disseminated intravascular coagulation syndrome

immune system disorders: very common – minor hypersensitivity reactions, mainly manifested as hyperemia (“rush” of blood) and skin rash; infrequent – significant hypersensitivity reactions requiring treatment (e.g., decreased blood pressure (BP), angioedema, respiratory dysfunction, generalized urticaria, swelling, back pain, chills, tachycardia, abdominal pain, pain in the extremities, profuse sweating); rare* – anaphylactic reactions (including fatal); very rare* – anaphylactic shock.

Nervous system disorders: very common – neurotoxicity (mainly peripheral neuropathy); rare* – motor neuropathy (leading to minor weakness of the limbs); very rarely* – confusion, autonomic neuropathy manifested by paralytic bowel obstruction and orthostatic hypotension, grand small type epileptic seizures, seizures, encephalopathy, dizziness, headache, ataxia.

Cardiovascular side: very common – ECG changes, decreased BP; common – bradycardia; infrequent – increased BP, thrombosis, thrombophlebitis, cardiomyopathy, asymptomatic ventricular tachycardia, tachycardia with behemia, atrioventricular block and syncope, myocardial infarction; rare – heart failure; very rare* – atrial fibrillation, supraventricular tachycardia, shock.

Respiratory system: rarely* – shortness of breath, pleural effusion, respiratory failure, interstitial pneumonia, pulmonary fibrosis, pulmonary embolism; very rarely* – cough.

Gastrointestinal tract side: very frequently, nausea, vomiting, diarrhea, mucositis; rarely*, intestinal obstruction, bowel perforation, ischemic colitis, pancreatitis; very rarely*, mesenteric artery thrombosis, pseudomembranous colitis, neutropenic colitis, esophagitis, constipation, ascites, anorexia.

Hepatic and biliary tract disorders: very rarely* – hepatonecrosis (fatal), hepatic encephalopathy (fatal).

Visual side: very rare* – reversible optic nerve damage and/or visual disturbances (atrial fibrillation scotoma or ocular migraine); frequency unknown* – macular edema, photopsia, vitreous body destruction.

Hearing organ: very rare* – hearing loss, tinnitus, vertigo (vestibular vertigo), ototoxicity.

Skin and subcutaneous tissue: very common – alopecia; common – temporary minor changes in the skin and nails; rare* – itching, rash, erythema, phlebitis, inflammation of subcutaneous fatty tissue, skin exfoliation, skin necrosis and fibrosis, skin lesions resembling the effects of radiation therapy; very rare* – Stevens-Johnson syndrome, epidermal necrolysis, erythema multiforme exudative, exfoliative dermatitis, urticaria, onycholysis; frequency unknown* – scleroderma, cutaneous lupus erythematosus, palmar and plantar erythrodysesthesia syndrome.

Muscular system disorders: very common – arthralgia, myalgia; frequency unknown* – systemic lupus erythematosus.

Termal reactions: frequently – local edema, pain, erythema, induration.

From the laboratory side: frequent – increased aspartate aminotransferase (AST) activity, increased alkaline phosphatase activity; infrequent – increased concentration of bilirubin; frequent* – increased concentration of serum creatinine.

Others: very common – accession of secondary infections (in single cases, fatal); infrequent – septic shock; rare* – pneumonia, sepsis, peritonitis, asthenia, general malaise, increased body temperature, dehydration, peripheral edema; frequency unknown* – tumor lysis syndrome.

Side effects in combination therapy:

Paclitaxel-Teva + cisplatin in 1st-line therapy for ovarian cancer

. The frequency and severity of neurotoxicity, arthralgia/myalgia and hypersensitivity are higher compared to therapy with cyclophosphamide and cisplatin. In contrast, myelosuppression is less frequent and less severe than with cyclophosphamide and cisplatin.

Manifestations of severe neurotoxicity when used in combination with cisplatin at a dose of 75 mg/m2 are less common when using Paclitaxel-Teva at a dose of 135 mg/m2 as a 24-hour infusion than when administered at a dose of 175 mg/mL2 as a 3-hour infusion.

Paclitaxel-Teva + trastuzumab in breast cancer therapy

. When Paclitaxel-Teva was used in combination with trastuzumab for first-line therapy of metastatic breast cancer, the following side effects were noted more frequently than with Paclitaxel-Teva monotherapy Heart failure, infections, chills, fever, cough, rash, arthralgia, tachycardia, diarrhea, increased BP, nasal bleeding, acne, herpetic rash, accidental injury, insomnia, rhinitis, sinusitis, injection site reactions.

Paclitaxel-Teva in combination with trastuzumab in 2nd-line therapy (after anthracycline drugs) resulted in increased frequency and severity of cardiac abnormalities (in rare cases with fatal outcome) compared to Paclitaxel-Teva monotherapy. In most cases, the side effects were reversible after appropriate treatment.

Paclitaxel-Teva + doxorubicin in breast cancer therapy

There have been cases of congestive heart failure in patients who have not previously received chemotherapy. Patients who had received prior chemotherapy courses, especially with anthracyclines, often had cardiac dysfunction, decreased left ventricular ejection fraction and ventricular function failure. Rarely, myocardial infarction has been noted.

Paclitaxel-Teva + radiation therapy

Patients who were simultaneously treated with Paclitaxel-Teva and radiation therapy had cases of radiation pneumonitis.

*Note: Post-marketing data on side effects are marked with an asterisk.

Overdose

Pregnancy use

Similarities