Medicinal Products

PAXENE 6 mg / mL

Generic drug of the therapeutic class: Oncology and Hematology
active ingredients: Paclitaxel
laboratory: Norton Healthcare Ltd

Solution for solution for IV infusion
Box of 1 bottle of 50 ml
All forms


Paxene is indicated for the treatment of patients with:
- AIDS-related Kaposi's sarcoma (AIDS-SK) at an advanced stage after failure of treatment with liposomal anthracycline,
- metastatic breast cancer (CMS) after failure or non-compliance with conventional treatment containing anthracyclines, - advanced ovarian cancer (OAC) or residual (> 1 cm) after initial laparotomy, in combination with cisplatin as a first-line treatment, - metastatic ovarian cancer (CMO) after failure of a platinum-based treatment without taxane as a second-line treatment,
- non-small cell lung cancer (NSCLC), in combination with cisplatin, who are not candidates for potentially curative surgery and / or radiotherapy. Limited efficacy data support this indication, a summary of significant studies is described in the pharmacodynamic properties section.

Dosage PAXENE 6 mg / mL Concentrate for solution for infusion IV Box of 1 bottle of 50 ml

- Dosage and route of administration:
. Paxene should be administered only under the supervision of a qualified oncologist, in units specialized in the administration of cytotoxic agents (see instructions for use, handling and disposal).
. Prior to Paxene administration, all patients should be premedicated with corticosteroids, antihistamines and H2 blockers. The following premedication is recommended: dexamethasone (8-20 mg) orally (12 and 6 hours) or intravenously (30-60 min) prior to administration of Paxene, 10 mg intravenous chlorpheniramine or an equivalent antihistamine 30 at 60 minutes before administration of Paxene and cimetidine (300 mg) or ranitidine (50 mg) intravenously 30 to 60 minutes before administration of Paxene. Appropriate drugs should be readily available in case of severe hypersensitivity reactions.
. Paxene should be administered using an infusion control device (pump), including tubing, and non-PVC connectors. The infusion line should be equipped with a microporous membrane filter with a maximum diameter of 0.22 μm during infusion of Paxene (see instructions for use, handling and disposal).
. If combined with cisplatin, see the Summary of Characteristics of cisplatin in advanced ovarian cancer and non-small cell lung cancer.
. AIDS-related Kaposi's sarcoma :
The recommended dose of Paxene is 100 mg / m² given as an intravenous infusion every 3 weeks.
. Metastatic breast or ovarian cancer (second-line) :
The recommended dose of Paxene is 175 mg / m² given as an intravenous infusion every 3 weeks.
. Advanced ovarian cancer (first-line) :
Although other regimens / combinations are currently being evaluated, a combination of Paxene and cisplatin is recommended. Depending on the duration of infusion, two doses of Paxene are recommended: Paxene 175 mg / m² intravenous infusion for 3 hours, followed by cisplatin 75 mg / m² every 3 weeks or Paxene 135 mg / m² infusion 24 hours, followed by cisplatin 75 mg / m² every 3 weeks.
. Advanced non-small cell lung cancer :
The recommended dose of Paxene is 175 mg / m² administered as a 3 hour intravenous infusion followed by cisplatin at a dosage of 80 mg / m² every 3 weeks.
- Dosage adjustments during treatment:
. Metastatic breast, ovarian and non-small cell lung cancer :
Paxene treatment cycles should not be repeated until the neutrophil count is at least 1500 cells / mm3 and the platelet count is at least 100, 000 cells / mm3. The dose of Paxene should be reduced by 20% (NSCLC and first intention of ovarian cancer) and by 25% (CMO and CMS) for subsequent Paxene cycles in patients with severe neutropenia (neutrophils <500 cells). / mm3 for a week or more), or severe peripheral neuropathy. Patients with mucositis (grade 2 or greater) during treatment with Paxene should have a 25% reduction in the dose for subsequent Paxene cycles.
. AIDS-related Kaposi's sarcoma :
Paxene treatment cycles should not be repeated until the neutrophil count is at least 1000 cells / mm3 and the platelet count is at least 75000 cells / mm3. The dose of Paxene should be reduced by 25%, that is, lowered to 75 mg / m² for the following cycles in patients with severe neutropenia (neutrophils <500 cells / mm3 for one week or more), severe peripheral neuropathy or mucositis (grade 3 or greater) during treatment with Paxene.
- Populations at risk:
. Patients with hepatic impairment :
There are no adequate data available to recommend dose adjustment in patients with mild to moderate hepatic impairment (see warnings and precautions for use and pharmacokinetics).
Patients with severe hepatic dysfunction should not be treated with paclitaxel.
. Patients with renal insufficiency :
To date, there are no studies in patients with renal impairment and the available information does not allow for a dose adjustment recommendation (see pharmacokinetic properties).
. Pediatric use : Tolerance and efficacy have not been established in children and adolescents (under 18 years of age). Paclitaxel is therefore not recommended for pediatric use.

Against indications

- History of severe hypersensitivity to paclitaxel or polyoxyethylene castor oil.
- Severe hepatic insufficiency.
- Initial neutropenia <1500 cells / mm3 (<1000 cells / mm3 in AIDS-SK patients).
- concomitant, serious and uncontrolled infection.
- Pregnancy and breast feeding :
. pregnancy: paclitaxel at the intravenous dose of 0.6 mg / kg / day resulted in reproductive toxicity and fetal development in the rat. Paxene is contraindicated in pregnancy. Women on Paxene should use effective contraception to prevent pregnancy during the course of treatment and should inform their GP immediately if this occurs.
. breastfeeding: Paxene is contraindicated during breastfeeding. The passage in breast milk is not known. Breastfeeding should be discontinued while taking Paxene.
Pediatric use: Tolerance and efficacy have not been established in children and adolescents (under 18 years of age). Paclitaxel is therefore not recommended for pediatric use.

Paxene side effects

- The following effects were observed in 166 CMS patients and 120 CMO patients treated as second-line therapy with 175 mg / m² of Paxene administered as a 3-hour infusion in 2 clinical studies and were considered possibly or probably related to Paxene. Since the AIDS-SK patient population is very specific, the safety data of a clinical study on 107 patients are presented separately at the end of the adverse effects section.
- Myelosuppression was the main dose-limiting toxicity of Paxene. Severe neutropenia (<500 cells / mm3) was observed in 26% of patients treated with Paxene during the treatment period. 19% of patients experienced severe neutropenia for more than 7 days. Thrombocytopenia was observed in 6% of patients. Two percent of patients presented a nadir for platelets <50000 cells / mm3. Anemia (Hb <11 g / dl) was observed in approximately 9% of patients and was severe in less than 1% (Hb <8 g / dl).
- Neuropathy was observed in 18% of patients treated with Paxene. Paresthesia was observed in 48% of patients. Severe neuropathy and severe paresthesia in 3% and 5% of patients respectively. Peripheral neuropathy may occur after the first cycle and may worsen during treatment with paclitaxel. In a few cases peripheral neuropathies resulted in discontinuation of treatment. Sensory symptoms usually improved within a few months after stopping treatment. Pre-existing neuropathies due to previous treatments are not a contraindication to paclitaxel therapy.
- The other most common neurological effect observed with Paxene was drowsiness in 14% of patients.
- Arthralgia was reported in 32% of patients (5% severe) and myalgia was observed in 47% (6% severe).
- Injection site reactions, including reactions secondary to extravasation, were generally mild and consisted of erythema, tenderness, skin depigmentation, or edema at the injection site that could lead to cellulitis. The recurrence of skin reactions at the site of anterior extravasation following administration of paclitaxel at another site, namely "recurrence", has been rarely reported. There is currently no specific treatment for extravasation reactions.
- The following table lists the adverse effects associated with the administration of paclitaxel monotherapy as a 3-hour infusion at the metastatic stage (286 patients treated in clinical studies with Paxene and 812 patients treated in other clinical studies with paclitaxel), and those reported during post-marketing surveillance for paclitaxel (*). When the effect is different between Paxene and other paclitaxel clinical studies, the most common incidence is reported.
- The frequency of adverse reactions listed below is presented according to the following convention:
Very common (> = 1/10) frequent (> = 1/100, = 1/1000, = 1/10000, <1/1000); very rare (<1/10000), including isolated cases. - Infections and infestations:
. Very common : infections (including herpes simplex, oral candidiasis, pharyngitis, rhinitis).
. Frequent : flu-like syndrome.
. Uncommon : severe infections, septic shock.
. Rare (*) : pneumonia.
- Blood and lymphatic system:
. Very common : severe neutropenia, severe leukopenia, thrombocytopenia, anemia, myelosuppression.
. Common : neutropenic fever
. Uncommon : severe anemia.
. Very rare (*) : acute myeloid leukemia, myelodysplastic syndrome.
- Effects on the immune system:
. Very common : minor hypersensitivity reactions (mainly redness and rash).
. Uncommon : hypersensitivity (delayed), significant hypersensitivity reactions requiring treatment (eg, hypotension, angioneurotic edema, respiratory distress, generalized urticaria).
. Rare (*) : anaphylactic reactions.
. Very rare (*) : anaphylactic shock (including fatal hypersensitivity).
- Effects on metabolism and nutrition:
. Very common : anorexia.
. Uncommon : dehydration, loss and weight gain.
- Psychiatric effects:
Very rare (*) : confusional state.
- Effects on the nervous system:
. Very common : neuropathy (mainly peripheral), paresthesia, somnolence.
. Common : Severe neuropathy (mainly peripheral), dizziness, nervousness, insomnia, depression, abnormal thinking, hypokinesia, abnormal gait, hyperesthesia, taste modification, headache.
. Rare (*) : motor neuropathy (giving rise to minor distal weakness).
. Very rare (*) : acute encephalopathy, autonomic neuropathy (giving rise to paralytic ileus and orthostatic hypotension), generalized seizures.
- Effects on sight:
. Uncommon : dry eyes, amblyopia, abnormal visual field.
. Very rare (*) : disorders of the optic nerve and / or visual (scintillating scotoma), especially in patients who received doses higher than those recommended.
- Effects on the ear and labyrinth:
. Frequent : tinnitus.
. Very rare (*) : deafness of perception, vertigo.
- Cardiac effects:
. Frequent : tachycardia, palpitation, bradycardia, syncope.
. Uncommon : congestive heart failure, cardiomyopathy, asymptomatic ventricular tachycardia, tachycardia with bigemina, atrioventricular block and syncope, myocardial infarction.
. Very rare (*) : atrial fibrillation.
- Vascular effects:
. Very common : hypotension.
. Common : vasodilation (redness)
. Uncommon : thrombophlebitis, hypertension, thrombosis.
. Very rare (*) : shock.
- Respiratory, thoracic and mediastinal effects:
. Frequent : dyspnea, epistaxis.
. Rare : pleural effusion, pulmonary fibrosis.
. Very rare (*) : cough, pulmonary hypertension.
- Gastrointestinal effects:
. Very common : nausea, vomiting, diarrhea, inflammation of the mucous membranes, constipation, stomatitis, abdominal pain.
. Frequent : dry mouth, ulceration of the mouth, melaena, dyspepsia.
. Very rare (*) : intestinal obstruction, intestinal perforation, pseudomembranous colitis, ischemic colitis, mesenteric thrombosis, necrotizing enterocolitis, oesophagitis, ascites, acute pancreatitis.
- Hepatobiliary effects:
Very rare (*) : hepatic necrosis, hepatic encephalopathy.
- Effects on the skin and subcutaneous tissue:
. Very common : alopecia.
. Common : transient skin changes, dry skin, exfoliating dermatitis, pruritus, rash, acne, transient and slight changes in nails.
. Uncommon : change in pigmentation or discoloration of the nail.
. Rare (*) : erythema.
. Very rare (*) : Stevens-Johnson syndrome, epidermal necrolysis, erythema multiforme, urticaria, onycholysis (patients on treatment must protect their hands and feet from the sun).
- Musculoskeletal and Cartilaginous Effects:
. Very common : arthralgia, myalgia.
. Frequent : bone pain, leg cramps, myasthenia, back pain.
- Kidney and urinary effects:
Common : dysuria.
- General and administrative site effects:
. Very common : asthenia, pain, edema including peripheral and facial.
. Common : Moderate reactions at the injection site (erythema, tenderness, skin discolouration or edema, pain, extravasation may lead to cellulitis and skin ulceration), malaise, chest pain, chills, fever.
- Lab parameters:
. Frequent : Severe elevation of transaminases, severe elevation of alkaline phosphatase.
. Uncommon : Severe elevation of bilirubin.
- The following results are from 2 major studies in first-line ovarian cancer (paclitaxel + cisplatin: more than 1050 patients) and 2 phase III studies in the treatment of advanced NSCLC (paclitaxel + cisplatin: more than 360 patients ) (see pharmacodynamic properties).
- After 3-hour infusion of first-line ovarian cancer, cases of neurotoxicity, arthralgia / myalgia, and hypersensitivity are more frequent and severe in patients treated with paclitaxel followed by cisplatin than in patients treated with cyclophosphamide followed by cisplatin. Myelosuppression is less frequent and less severe with paclitaxel infused over 3 hours followed by cisplatin compared to cyclophosphamide followed by cisplatin.
- Neurotoxicity, mainly peripheral neuropathy, appears to be more frequent and severe with an infusion of 175 mg / m² over 3 hours (85% neurotoxicity, 15% severe) than with an infusion of 135 mg / m² over 24 hours (25 % peripheral neuropathies, 3% severe) paclitaxel associated with cisplatin. There is an apparent increase in the incidence of severe neurotoxicity in patients with NSCLC and in ovarian cancer patients treated with paclitaxel over 3 hours, followed by cisplatin. Peripheral neuropathy can occur following the first course of paclitaxel and worsen during subsequent courses. It motivated the discontinuation of treatment in a few cases. Sensory effects generally decreased or disappeared a few months after the end of treatment. Pre-existing neuropathy resulting from previous treatments does not contraindicate treatment with paclitaxel.
- In 8 published clinical trials (8 phase III trials) including 4735 patients with advanced ovarian cancer and 12 published clinical trials (1 large phase II trial and 11 phase III trials) including 4315 NSCLC patients treated with paclitaxel and platinum-salt treatments, similar adverse events were observed compared with paclitaxel monotherapy. In addition, ileus, abnormalities in creatinine clearance, and electrolytes (eg, hyponatremia, hypomagnesemia), hyperglycemia, cough, and pneumonia are rarely seen.
- Cases of pneumonia in patients receiving concomitant radiotherapy and / or gemcitabine have been reported very rarely.
- It is possible or likely that the following adverse events, observed in 107 patients with AIDS-SK treated in a second-line clinical trial with 100 mg / m² of Paxene given as a 3-hour infusion, are related to Paxene. With the exception of haematological and hepatic events (see below), the frequency and severity of adverse events in AIDS-SK patients were generally similar to those seen in patients with other solid tumors treated with paclitaxel. as monotherapy.
- Myelosuppression was the major dose-limiting side effect of Paxene. Severe neutropenia (<500 cells / mm3) was observed in 20% and 39% of patients respectively during the first treatment cycle and the entire treatment. Neutropenia was present for more than 7 days in 41% of patients and for 30-35 days in 8% of patients. It was corrected in 35 days in all patients followed. The incidence of grade 4 neutropenia lasting 7 days or longer was 22%. Paxene-related neutropenic fever was reported in 14% of patients. There were 3 serious seizures (2.8%) during Paxene administration. Thrombocytopenia was observed in 50% of patients and was severe (<50000 cells / mm3) in 9% of cases. Localized bleeding episodes associated with Paxene have been reported in <3% of cases. Anemia (Hb <11 g / dl) was observed in 61% of patients and was severe (Hb <8 g / dl) in 10% of patients. Blood transfusion was required in 21% of patients.
- Of the patients (> 50% on protease inhibitors) with normal liver function at baseline, 28%, 43% and 44% had elevations in bilirubin, alkaline phosphatase and AST (SGOT), respectively. For each of these parameters, the increase was severe in 1% of cases.

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