Paclitaxel-Teva, 6 mg/ml 16.7ml

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.

AIDS-related Kaposi’s sarcoma

.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.

Because extravasation of the drug may occur during administration, close monitoring of the infusion area for signs of possible infiltration is recommended.

Paclitaxel-Teva should be used as a diluted solution. Patients should be premedicated with glucocorticosteroids, H1

and H2-histamine receptor blockers before the drug is administered. If Paclitaxel-Teva is used in combination with cisplatin, Paclitaxel-Teva should be administered first, followed by cisplatin.

Anaphylaxis and serious hypersensitivity reactions

Less than 1% of patients have had serious hypersensitivity reactions during treatment with Paclitaxel-Teva despite premedication. The frequency and severity of such reactions were independent of the dose and route of administration of the drug. When severe reactions developed, choking, hot flashes, chest pain, tachycardia, as well as abdominal pain, pain in the extremities, increased sweating, and increased BP were the most frequently observed.

In case of severe hypersensitivity reactions, administration of Paclitaxel-Teva should be stopped immediately and symptomatic treatment should be administered if necessary; in such cases repeated courses of treatment with the drug should not be prescribed.

Injection site reactions

The following usually mild injection site reactions have been observed during intravenous administration of the drug: swelling, injection site pain, erythema, injection site sensitivity, injection site thickening, hemorrhage, which may lead to development of cellulitis. Such reactions were more frequently observed with a 24-hour infusion than with a 3-hour infusion. In some cases, the onset of such reactions was observed both during the infusion and 7-10 days after it.

Intra-arterial administration of paclitaxel should be avoided because severe tissue reactions have been observed in animals after intra-arterial administration in local tolerability studies.

Myelosuppression

The suppression of bone marrow function (mainly neutropenia) depends on the dose and route of administration of the drug and is a major toxic dose-limiting reaction. For example, when cisplatin at a dose of 75 mg/m2 and Paclitaxel-Teva at a dose of 175 mg/m2 as a 3-hour infusion, severe neurotoxicity was observed more frequently than when Paclitaxel-Teva was administered at a dose of 135 mg/m2 as a 24-hour infusion, i.e.i.e., the duration of infusion has a more significant effect on the risk of myelosuppression than the dose. In patients with a history of prior radiotherapy, neutropenia developed less frequently and to a milder degree, and did not worsen as the drug accumulated in the body. Patients with ovarian cancer had a higher risk of renal failure when using the combination of Paclitaxel-Teva + cisplatin compared to cisplatin monotherapy. Infections have been observed very frequently and sometimes with fatal outcome, including sepsis, pneumonia and peritonitis. Urinary tract and upper respiratory tract infections were reported as the most frequent complicated infections. At least one opportunistic infection was noted in immunosuppressed patients, patients with HIV infection, and patients with AIDS-related Kaposi’s sarcoma.

The use of maintenance therapy, including granulocyte colony-stimulating factor, is recommended for patients who have had severe neutropenia.

Decrease of platelet count below 100000/μL has been noted at least once during all therapy with Paclitaxel-Teva; sometimes platelet count has been below 50000/μL. There have also been cases of bleeding, most of which were local, and their incidence was not associated with the dose of Paclitaxel-Teva and the regimen of administration. When using Paclitaxel-Teva, the blood count should be monitored regularly. Patients with a neutrophil count of less than 1500/μL and less than 1000/μL in AIDS-related Kaposi sarcoma and a platelet count of less than 100000/μL (75000/μL in patients with AIDS-related Kaposi sarcoma) should not be treated.

If severe neutropenia (less than 500/µL) or severe peripheral neuropathy develops during treatment with Paclitaxel-Teva, a 20% dose reduction is recommended for subsequent courses of therapy (25% in patients with AIDS-related Kaposi sarcoma).

Effects on the cardiovascular system

The decrease, increase in BP and bradycardia seen during administration of Paclitaxel-Teva are usually asymptomatic and in most cases do not require treatment. Decreased BP and bradycardia were usually observed during the first 3 hours of infusion. ECG abnormalities in the form of repolarization disorders such as sinus tachycardia, sinus bradycardia and early extrasystole have also been observed. In severe cases, treatment with Paclitaxel-Teva should be suspended or discontinued. Monitoring of vital signs is recommended, especially during the first hour of infusion. If the drug Paclitaxel-Teva is used in combination with trastuzumab or doxorubicin for treatment of metastatic breast cancer, monitoring of cardiac function is recommended.

There have been cases of severe cardiac conduction abnormalities during treatment with Paclitaxel-Teva. If symptoms of cardiac conduction abnormalities are detected, patients should receive appropriate therapy along with continuous ECG monitoring of the cardiovascular system.

Influence on the nervous system

The frequency and severity of nervous system disorders were mostly dose-dependent. Peripheral neuropathy, usually moderately severe, was frequently noted during treatment with Paclitaxel-Teva. The incidence of peripheral neuropathy increased as the drug accumulated in the body. Paresthesias and hyperesthesias were frequently observed. It is recommended to decrease the dose by 20% during the following courses of the treatment (in patients with Kaposi’s sarcoma caused by AIDS – by 25%) if severe neuropathy is observed. Peripheral neuropathy may be the reason for discontinuation of therapy with Paclitaxel-Teva. Symptoms of neuropathy decreased or completely disappeared within several months after discontinuation of therapy with the drug. The development of neuropathy in previous therapy is not a contraindication for the prescription of Paclitaxel-Teva.

Rarely, there have been cases of impaired evoked optic potential in patients with persistent optic nerve damage.

Possible effects of ethanol contained in the drug Paclitaxel-Teva should be taken into account.

Influence on the gastrointestinal tract

Mild to moderate cases of nausea/vomiting, diarrhea, mucositis were very common in all patients. The incidence of mucositis depended on the route of administration of the drug and was more frequently observed with a 24-hour infusion than with a 3-hour infusion.

Rare cases of neutropenic enterocolitis (tiflitis), despite coadministration of granulocytic colony-stimulating factor, were observed in patients receiving Paclitaxel-Teva as monotherapy and in combination with other chemotherapeutic agents.

Hepatic impairment

Patients with hepatic impairment are a risk group associated with the severity of side effects, especially grade 3-4 myelosuppression. The patient’s condition should be monitored closely and adjustments to the drug dose should be considered if necessary.

Radiation pneumonitis has been reported with concomitant radiation therapy.

Patients should use reliable contraceptive methods during treatment with Paclitaxel-Teva and for at least 3 months after completion of therapy.

There is no information about treatment with the drug in patients with baseline severe cholestasis. Therapy with paclitaxel is prohibited in patients with severe hepatic dysfunction.

Vaccination

. Co-administration of Paclitaxel-Teva and live virus vaccines may potentiate replication of the vaccine virus and/or may increase the side effects of the vaccines because normal defense mechanisms may be inhibited by Paclitaxel-Teva. Vaccination with live virus vaccines in patients using Paclitaxel-Teva can lead to the development of severe infections. The patient’s immune response may be reduced when this vaccine is administered.

The use of live vaccines in these patients should be avoided and a specialist should be consulted.

Fertility

In view of the possible mutagenic effect of Paclitaxel-Teva, effective contraception should be recommended in patients of both sexes during therapy with Paclitaxel-Teva and for 6 months after completion of therapy. Cryopreservation of sperm may also be recommended due to a possible reduction in fertility in men to enable conception of a child in the future.

Influence on the ability to drive vehicles and mechanisms

Paclitaxel-Teva contains ethanol, therefore, during treatment one should refrain from driving and operating potentially dangerous mechanisms.

Premedication of the patient before initiation of Paclitaxel-Teva may also have an adverse effect on ability to concentrate.

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