Yondelis

Yondelis

Manufacturer:

Johnson & Johnson

Distributor:

DCH Auriga - Healthcare
/
Four Star

Marketer:

Janssen
Full Prescribing Info
Contents
Trabectedin.
Description
Each mL of reconstituted solution contains trabectedin 0.05 mg. Yondelis also contains the following excipients: Sucrose, potassium dihydrogen phosphate; phosphoric acid and potassium hydroxide for pH adjustment.
Action
Pharmacotherapeutic Group: Antineoplastic agent. ATC Code: L01CX01.
Pharmacology: Pharmacodynamics: Mechanism of Action: Trabectedin binds to the minor groove of DNA, bending the helix to the major groove. This binding to DNA triggers a cascade of events affecting several transcription factors, DNA binding proteins and DNA repair pathways, resulting in perturbation of the cell cycle. Trabectedin has been shown to exert antiproliferative in vitro and in vivo activity against a range of human tumour cell lines and experimental tumours, including malignancies eg, sarcoma, breast, non-small cell lung, ovarian and melanoma.
Clinical Efficacy: The efficacy and safety of trabectedin is based on a randomized trial in patients with locally advanced or metastatic liposarcoma or leiomyosarcoma, whose disease had progressed or relapsed after treatment with at least anthracyclines and ifosfamide. In this trial, trabectedin was administered either at 1.5 mg/m2 as a 24-hr IV infusion every 3 weeks or at 0.58 mg/m2 weekly as a 3-hr IV infusion for 3 weeks of a 4-week cycle. The protocol specified final time to progression (TTP) analysis showed a 26.6% reduction in the relative risk of progression for patients treated in the 24-hr every 3 weeks group (hazard ratio=0.734 CI: 0.554-0.974). Median TTP values were 3.7 months (CI: 2.1-5.4 m) in the 24-hr every 3 weeks group and 2.3 months (CI: 2-3.5 m) in the 3-hr weekly group (p=0.0302). No significant differences were detected in overall survival (OS). Median OS with the 24-hr every 3 weeks regime was 13.9 months (CI: 12.5-18.6) and 60.2% of patients were alive at 1 year (CI: 52.0%-68.5%).
Additional efficacy data are available from 3 single-arm phase II trials with similar populations treated with the same regime. These trials evaluated a total of 100 patients with lipo- and leiomyosarcoma and 83 patients with other types of sarcoma.
Pharmacokinetics: Systemic exposure after administration as a 24-hr constant rate IV infusion is dose proportional at doses up to and including 1.8 mg/m2. Trabectedin pharmacokinetic profile is consistent with a multiple-compartment disposition model.
Distribution: Following IV administration, trabectedin demonstrates a high apparent volume of distribution, consistent with extensive tissue and plasma protein binding (94-98% of trabectedin in plasma is protein bound). The distribution volume at steady state of trabectedin in human subjects exceeds 5000 L.
Metabolism: Cytochrome P-450 (CYP-450) 3A4 is the major CYP-450 isozyme responsible for the oxidative metabolism of trabectedin at clinically relevant concentrations. Other P450 enzymes may contribute to metabolism. Trabectedin does not induce or inhibit major CYP450 enxymes.
Elimination: Renal elimination of unchanged trabectedin in humans is low (<1%). The terminal t½ is long (population value of the terminal elimination phase: 180-hr). After a dose of radiolabelled trabectedin administered to cancer patients, faecal mean (SD) recovery of total radioactivity is 58% (17%), and urinary mean (SD) recovery is 5.8% (1.73%). Based on the population estimate for plasma clearance of trabectedin (31.5 L/hr) and blood/plasma ratio (0.89), the clearance of trabectedin in whole blood is approximately 35 L/hr. This value is approximately ½ the rate of human hepatic blood flow. Thus, the trabectedin extraction ratio can be considered moderate. The interpatient variability of the population estimate for plasma clearance of trabectedin was 51% and intrapatient variability was 28%.
Special Populations: A population pharmacokinetic analysis indicated that the plasma clearance of trabectedin is not influenced by age (range 19-83 years) or gender. The effects of race and ethnicity on trabectedin pharmacokinetics have not been studied.
Renal Impairment: There is no relevant influence of renal function measured by CrCl on trabectedin pharmacokinetics within the range of values (≥34.4 mL/min) present in the patients included in the clinical studies. No data are available in patients with a CrCl of <34.4 mL/min. The low recovery (<9% in all studied patients) of total radioactivity in the urine after a single dose of 14C-labelled trabectedin suggests that renal impairment would have little influence on the elimination of trabectedin or its metabolites.
Hepatic Impairment: Although the population analysis showed no relationship between serum liver enzyme concentrations and the plasma clearance of trabectedin, systemic exposure to trabectedin may be increased in patients with hepatic impairment; therefore, close monitoring of toxicity is warranted.
Toxicology: Preclinical data indicate that trabectedin has limited effect on the cardiovascular, respiratory and CNS at exposures below the therapeutic clinical range, in terms of AUC.
The effects of trabectedin on cardiovascular and respiratory function have been investigated in vivo (anesthetized Cynomolgus monkeys). A 1-hr infusion schedule was selected to attain maximum plasma levels (Cmax values) in the range of those observed in the clinic. The plasma trabectedin levels attained were 10.6±5.4 (Cmax), higher than those reached in patients after infusion of 1500 mcg/m2 for 24 (Cmax of 1.8±1.1 ng/mL) and similar to those reached after administration of the same dose by 3-hr infusion (Cmax of 10.8±3.7 ng/mL).
Myelosupression and hepatotoxicity were identified as the primary toxicity for trabectedin. Findings observed included haematopoietic toxicity (severe leukopenia, anaemia, lymphoid and bone marrow depletion) as well as increases in liver function tests, hepatocellular degeneration, intestinal epithelial necrosis and severe local reactions at the injection site. Renal toxicological findings were detected in multi-cycle toxicity studies conducted in monkeys. These findings were secondary to severe local reaction at the administration site, and therefore, uncertainly attributable to trabectedin; however, caution must be guaranteed in the interpretation of these renal findings and treatment-related toxicity cannot be excluded.
Trabectedin is genotoxic both in vitro and in vivo. Long-term carcinogenicity studies have not been performed.
Fertility studies with trabectedin were not performed but limited histopathological changes were observed in the gonads in the repeat dose toxicity studies. Considering the nature of the compound (cytotoxic and mutagenic), it is likely to affect the reproductive capacity.
Indications/Uses
Treatment of patients with advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide, or who are unsuited to receive these agents. Efficacy data are based mainly on liposarcoma and leiomyosarcoma patients.
Dosage/Direction for Use
Yondelis must be administered under the supervision of a physician experienced in the use of chemotherapy. Its use should be confined to personnel specialized in the administration of cytotoxic agents.
Recommended Starting Dose: 1.5 mg/m2 body surface area, administered as an IV infusion over 24 hrs with a 3-week interval between cycles. Administration through a central venous line is strongly recommended (see Precautions).
All patients must be premedicated with corticosteroids eg, dexamethasone IV 20 mg, 30 min before each Yondelis infusion; not only as antiemetic prophylaxis, but also because it appears to provide hepatoprotective effects. Additional antiemetics may be administered as needed.
The following criteria are required to allow treatment with Yondelis: Absolute neutrophil count (ANC) ≥1500/mm3; platelet count ≥100,000/mm3; bilirubin ≤ upper limit of normal (ULN); alkaline phosphatase ≤2.5 x ULN (consider hepatic isoenzymes 5-nucleotidase or GGT, if the elevation could be osseous in origin); albumin ≥25 g/L; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 x ULN; CrCl ≥30 mL/min; creatine phosphokinase (CPK) ≤2.5 x ULN; haemoglobin ≥9 g/dL.
The same criteria as above must be met prior to initiation of next cycles. Otherwise, treatment must be delayed for up to 3 weeks until the criteria are met. If these toxicities persist beyond 3 weeks, treatment discontinuation should be considered.
Additional monitoring of haematological parameters [alkaline phosphatase, bilirubin, CPK and aminotransferases (AST and ALT)] should occur weekly during the first 2 cycles of therapy and at least once between treatments in subsequent cycles.
The same dose should be given for all cycles provided that no grade 3-4 toxicities are seen and that the patient fulfills the re-treatment criteria.
Dose Adjustments During Treatment: Prior to re-treatment, patients must fulfill the baseline criteria defined previously. If any of the following events occur at any time between cycles, the dose must be reduced to 1.2 mg/m2 for subsequent cycles: Neutropenia <500/mm3 lasting for >5 days or associated with fever or infection; thrombocytopenia <25,000/mm3; increase of bilirubin >ULN and/or alkaline phosphatase >2.5 x ULN; increase of aminotransferases (AST or ALT) >2.5 x ULN which has not recovered by day 21; any other grade 3 or 4 adverse reactions (eg, nausea, vomiting, fatigue).
Once a dose has been reduced because of toxicity, dose escalation in the subsequent cycles is not recommended. If any of these toxicities reappear in subsequent cycles in a patient exhibiting clinical benefit, the dose may be further reduced to 1 mg/m2. In the event that further dose reductions are necessary, treatment discontinuation should be considered.
In clinical trials, there were no pre-defined limits to the number of cycles administered. Treatment continued whilst clinical benefit was noted. Trabectedin has been administered for 6 or more cycles in 168 out of 569 (29.5%) patients treated with the proposed dose and schedule. This regime has been used for up to 38 cycles. No cumulative toxicities have been observed in patients treated with multiple cycles.Elderly: No specific studies in elderly patients have been performed. Overall, 20% of the 1164 patients in the integrated safety analysis were >65 years. No relevant differences in the safety profile were seen in this patient population. Results from population pharmacokinetic analyses indicate that the plasma clearance and distribution volume of trabectedin are not influenced by age. Therefore, dose adjustments based uniquely on age criteria are not routinely recommended.
Patients with Impaired Hepatic Function: No studies with the proposed regime have been conducted in patients with liver dysfunction. Thus, data are not available to recommend a lower starting dose in patients with hepatic impairment.
However, special caution is advised and dose adjustments may be necessary in these patients since systemic exposure is probably increased and the risk of hepatotoxicity might be increased. Patients with elevated bilirubin at the time of initiation of cycle must not be treated with Yondelis (see Precautions).
Patients with Impaired Renal Function: Studies including patients with severe renal insufficiency (CrCl <30 mL/min) have not been conducted and therefore, Yondelis must not be used in this patient population (see Precautions). The pharmacokinetics of trabectedin are not expected to be impacted by mild or moderate renal impairment (see Pharmacokinetics under Actions).
Administration: Preparation of IV Infusion: Appropriate aseptic techniques must be used. Yondelis must be reconstituted and further diluted prior to infusion.
Reconstitution: A syringe is used to inject 20 mL of sterile water for injections into the vial. Shake the vial until complete dissolution. The reconstituted solution results in a clear, colourless or slightly yellowish solution, essentially free of visible particles. This reconstituted solution contains trabectedin 0.05 mg/mL. It requires further dilution and is for single-use only.
The reconstituted solution should be diluted with sodium chloride 9 mg/mL (0.9%) solution for infusion or glucose 50 mg/mL (5%) solution for infusion. The required volume should be calculated using the following equation:

Click on icon to see table/diagram/image

The appropriate amount of solution should be withdrawn from the vial and added to an infusion bag containing ≥500 mL of diluent [sodium chloride 9 mg/mL (0.9%) solution for infusion or glucose 50 mg/ml (5%) solution for infusion] if administration is to be made through a central venous line.
If central venous access is not feasible and a peripheral venous line has to be used, the reconstituted solution should be added to an infusion bag containing ≥1000 mL of diluent.
Parenteral solutions should be inspected visually for particles prior to administration. Once the infusion is prepared, it should be administered immediately.
Overdosage
There is limited data on the effects of trabectedin overdose. The major anticipated toxicities are gastrointestinal, bone marrow suppression and hepatic toxicity. There is no specific antidote for trabectedin currently available. In the event of an overdose, patients should be closely monitored and symptomatic supportive care measures instituted as required.
Contraindications
Patients with hypersensitivity to trabectedin or to any of the excipients, concurrent serious or uncontrolled infection. Combination with yellow fever vaccine (see Interactions).
Use in lactation: It is not known whether trabectedin is excreted in human milk. The excretion of trabectedin milk has not been studied in animals. Breast-feeding is contraindicated during treatment and 3 months thereafter.
Use in children: The safety and efficacy of trabectedin in pediatric patients have not yet been established. Therefore, Yondelis must not be used in children and adolescents until further data become available.
Special Precautions
Hepatic Impairment: Patients must meet specific criteria on hepatic function parameters to start treatment with Yondelis. Since systemic exposure to trabectedin is probably increased due to hepatic impairment and therefore, the risk of hepatotoxicity might be increased, patients with clinically relevant liver diseases eg, active chronic hepatitis, must be closely monitored and the dose adjusted if needed. Patients with elevated bilirubin at the time of initiation of the cycle must not be treated with trabectedin (see Dosage & Administration).
Renal Impairment: Creatinine clearance must be monitored prior to, and during treatment. Trabectedin must not be used in patients with CrCl <30 ml/min (see Dosage & Administration).
Neutropenia and Thrombocytopenia: Grades 3 or 4 neutropenia and thrombocytopenia associated with trabectedin therapy have been very commonly reported. A full blood cell count including differential and platelet count must be performed at baseline, weekly for the first 2 cycles and then once between cycles (see Dosage & Administration). Patients who develop fever should promptly seek medical attention. If this occurs, active supportive therapy should be started immediately.
Nausea and Vomiting: All patients must be premedicated with corticosteroids eg, dexamethasone. Additional antiemetics may be administered as needed (see Dosage & Administration).
Rhabdomyolysis and Severe CPK Elevations (>10 x ULN): Trabectedin must not be used in patients with CPK >2.5 ULN (see Dosage & Administration). Rhabdomyolysis has been uncommonly reported, usually in association with myelotoxicity, severe liver function test abnormalities and/or renal failure. Therefore, CPK should be closely monitored whenever a patient may be experiencing any of these toxicities. If rhabdomyolysis occurs, supportive measures eg, parenteral hydration, urine alkalinisation and dialysis should be promptly established as indicated. Treatment with Yondelis should be discontinued until the patient fully recovers.
Caution should be taken if medicinal products associated with rhabdomyolysis (eg, statins) are administered concomitantly with trabectedin, since the risk of rhabdomyolysis may be increased.
Liver Function Test (LFT) Abnormalities: Reversible acute increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) have been reported in most patients. Yondelis must not be used in patients with elevated bilirubin at the time of initiation of cycle. Patients with increases in AST, ALT and alkaline phosphatase between cycles may necessitate dose reduction (see Dosage & Administration).
Injection Site Reactions: The use of central venous access is strongly recommended (see Dosage & Administration). Patients may develop a potentially severe injection site reaction when trabectedin is administered through a peripheral venous line.
Others: Caution should be taken if medicinal products associated with hepatotoxicity are administered concomitantly with trabectedin, since the risk of hepatotoxicity may be increased. The concomitant use of trabectedin with alcohol must be avoided. This medicine contains potassium, <1 mmol (39mg) per vial, essentially "potassium-free".
Effects on Ability to Drive and Operate Machinery: No studies on the effects of the ability to drive and to use machines have been performed. However, fatigue and/or asthenia have been reported in patients receiving trabectedin. Patients who experience any of these events during therapy must not drive or operate machines.
Impairment of Fertility: Men in fertile age and women of childbearing potential must use effective contraception during treatment and 3 months thereafter for women and immediately inform the treating physician if a pregnancy occurs (see Toxicology under Actions) and 5 months after treatment for men.
Trabectedin can have genotoxic effects. Advice on conservation of sperm should be sought prior to treatment because of the possibility of irreversible infertility due to therapy with Yondelis.
If pregnancy occurs during treatment, genetic counseling should be considered. Genetic counseling is also recommended for patients wishing to have children after therapy.
Use in pregnancy: No sufficient clinical data on exposed pregnancies are available. However, based on its known mechanism of action, trabectedin may cause serious birth defects when administered during pregnancy. Trabectedin should not be used during pregnancy unless clearly necessary. If it is used during pregnancy, the patient must be informed of the potential risk to the foetus and be monitored carefully (see Toxicology under Actions). If trabectedin is used at the end of pregnancy, potential adverse reactions should be monitored carefully in the newborns.
Use In Pregnancy & Lactation
If pregnancy occurs during treatment, genetic counseling should be considered. Genetic counseling is also recommended for patients wishing to have children after therapy.
Use in pregnancy: No sufficient clinical data on exposed pregnancies are available. However, based on its known mechanism of action, trabectedin may cause serious birth defects when administered during pregnancy. Trabectedin should not be used during pregnancy unless clearly necessary. If it is used during pregnancy, the patient must be informed of the potential risk to the foetus and be monitored carefully (see Toxicology under Actions). If trabectedin is used at the end of pregnancy, potential adverse reactions should be monitored carefully in the newborns.
Use in lactation: It is not known whether trabectedin is excreted in human milk. The excretion of trabectedin milk has not been studied in animals. Breast-feeding is contraindicated during treatment and 3 months thereafter.
Adverse Reactions
Unless otherwise specified, the following safety profile of Yondelis is based on the evaluation in clinical trials of 569 patients treated up to April 2007 with the recommended treatment regime in several cancer types including soft tissue sarcoma, breast cancer, osteosarcoma, ovarian cancer, GIST, melanoma and renal carcinoma.
Approximately 91% of patients can be expected to have adverse reactions of any grade. Around 40% of patients are expected to have adverse reactions of grade 3 or 4 severity. The most common adverse reactions of any severity grade were nausea, fatigue, vomiting, anorexia, neuutropenia, and increases in AST/ALT.
Fatal adverse reactions have occurred in 1.9% of patients. They were often result of a combination of events including pancytopenia, febrile neutropenia, some of them with sepsis, hepatic involvement, renal failure and rhabdomyolysis.
Adverse reactions: The frequencies of the adverse reactions reported below are classified as very common (≥1/10), common (≥1/100 to <1/10) and uncommon (≥1/1000 to <1/100). The following are the adverse reactions reported in ≥1% of patients according to the standard MedDRA system organ class. Both adverse reactions and laboratory values have been used to provide frequencies. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Adverse Reactions Reported in ≥1% of Patients in Clinical Trials at the Recommended Regime (1.5 mg/m2, 24-hr infusion every 3 weeks): Investigations: Very Common: Increased blood creatine phosphokinase, increased blood creatinine; decreased blood albumin. Common: Decreased weight.
Blood and Lymphatic System Disorders: Very Common: Neutropenia, thrombocytopenia, anaemia, leukopenia. Common: Febrile neutropenia.
Nervous System Disorders: Very Common: Headache. Common: Peripheral sensory neuropathy, dysgeusia, dizziness, paraesthesia.
Respiratory, Thoracic and Mediastinal Disorders: Common: Dyspnoea, cough.
GI Disorders: Very Common: Vomiting, nausea, constipation. Common: Diarrhoea, stomatitis, abdominal pain, dyspepsia, upper abdominal pain.
Skin and Subcutaneous Tissue Disorders: Common: Alopecia.
Musculoskeletal and Connective Tissue Disorders: Common: Myalgia, arthralgia, back pain.
Metabolism and Nutrition Disorders: Very Common: Anorexia. Common: Dehydration, decreased appetite, hypokalemia.
Infections and Infestations: Common: Infection.
Vascular Disorders: Common: Hypotension, flushing.
General Disorders and Administration Site Conditions: Very Common: Fatigue, asthenia. Common: Pyrexia, oedema, oedema peripheral, injection site reaction.
Hepatobiliary Disorders: Very Common: Hyperbilirubinemia; increased ALT and AST, γ-glutamyltransferase.
Psychiatric Disorders: Common: Insomnia.
Most Frequent Adverse Reactions: Blood and Lymphatic System Disorders: Neutropenia: Neutropenia occurred in 77% of patients. Grades 3 and 4 neutropenia occurred in 26% and 24% of patients, respectively. The analysis per cycle showed that neutropenia of grade 3 and 4 occurred in approximately 19% and 8% of cycles respectively. Febrile neutropenia occurred in 2% of patients and in <1% of cycles. Neutropenia followed a predictable pattern of rapid onset and reversibility and was rarely associated with fever or infection.
Thrombocytopenia: Grades 3 and 4 thrombocytopenia occurred in 11% and 2% of patients, respectively. The analysis per cycle showed that thrombocytopenia of grade 3 and 4 occurred in approximately 3% and <1% of cycles respectively. Bleeding events associated to thrombocytopenia occurred in <1% of patients.
Anaemia: Anaemia occurred in 93% of patients although 46% of patients were anaemic at baseline. Grades 3 and 4 anaemia occurred in 10% and 3% of patients, respectively. The analysis per cycle showed that anaemia of grade 3 and 4 occurred in approximately 3% and 1% cycles respectively.
Hepatobiliary Disorders: AST/ALT Increases: Transient grade 3 increases of AST and ALT were observed in 38% and 44% of the patients and grade 4 elevations in 3% and 7% of the patients, respectively. The median time to reach the peak values was 5 days for both AST and ALT. Most of the values had decreased to grade 1 or resolved by day 14-15 (see Precautions). Grade 3 elevations of AST and ALT occurred in 12% and 20% of cycles respectively. Most transaminase elevations improved to grade 1 or to pre-retreatment levels within 15 days, and less than 2% of cycles had recovering times longer than 25 days. ALT and AST increases did not follow a cumulative pattern but showed a tendency towards less severe elevations over time.
Hyperbilirubinemia: Grades 1 to 2 bilirubin increases were observed in 23% of the patients. Grade 3 hyperbilirubinemia occurred in 1% of patients. Bilirubin peaks approximately a week after onset and resolves approximately 2 weeks after onset. Clinical manifestations of severe hepatic injury were uncommon with a <1% incidence of individual signs and symptoms including jaundice, hepatomegaly or liver pain. Mortality in the presence of hepatic injury occurred in <1% of patients.
Other Adverse Reactions: Nausea, Vomiting, Diarrhoea and Constipation: Nausea and vomiting were reported in 63% and 38.5% of patients, respectively. Grades 3-4 nausea and vomiting were reported in 6% and 6.5% of patients, respectively. Grades 3-4 diarrhoea and constipation were reported in <1% of patients.
Stomatitis: Grades 3-4 mucositis was reported in <1% of the patients.
Fatigue/Asthenia: Grades 3-4 fatigue/asthenia occurred in 9% and 1% of patients, respectively.
Anorexia: Grades 3-4 anorexia occurred in <1% of the patients.
CPK Elevations and Rhabdomyolysis: CPK elevations of any grade were observed in 26% of patients. Grades 3 or 4 increases of CPK were observed in 4% of patients. CPK increases in association with rhabdomyolysis were reported in <1% of patients.
Dyspnoea: Grades 3-4 dyspnoea reported as trabectedin related occurred in 2% of the patients.
Alopecia: Alopecia was reported in approximately 3% of all patients, of which the majority was grade 1 alopecia.
Drug Interactions
Effects of Other Substances on Trabectedin: In vivo interaction studies have not been performed. Since trabectedin is metabolized mainly by CYP3A4, co-administration of substances that inhibit this isoenzyme eg, ketoconazole, fluconazole, ritonavir or clarithromycin could decrease metabolism and increase trabectedin concentrations. If such combinations are needed, close monitoring of toxicities is required. Likewise, co-administration with potent inducers of this enzyme (eg, rifampicin, phenobarbital, St. John's wort) may decrease the systemic exposure to trabectedin.
Concomitant use of trabectedin with phenytoin may reduce phenytoin absorption leading to an exacerbation of convulsions. Combination of trabectedin with phenytoin or live attenuated vaccines is not recommended and with yellow fever vaccine is specifically contraindicated.
Alcohol consumption must be avoided during treatment with trabectedin due to the hepatotoxicity of the medicinal product.
Preclinical data have demonstrated that trabectedin is a substrate to P-gp. Concomitant administration of inhibitors of P-gp, eg, cyclosporine and verapamil, may alter trabectedin distribution and/or elimination. The relevance of this interaction eg, CNS toxicity has not been established. Caution should be taken in such situations.
Impact of Trabectedin on Co-Administered Drugs: In vitro trabectedin does not induce or inhibit major CYP-450 enzymes.
Incompatibilities: Yondelis must not be mixed or diluted with other medicinal products except with sterile water for injections, sodium chloride 0.9% and glucose solution 5%.
Caution For Usage
Instructions for Handling and Disposal: Yondelis is a cytotoxic anticancer medicinal product and, as with other potentially toxic compounds, caution should be exercised during handling. Procedures for proper handling and disposal of cytotoxic medicinal products must be followed. Personnel should be trained in the correct techniques to reconstitute and dilute the medicinal product and should wear protective clothing including mask, goggles and gloves during the reconstitution and dilution. Pregnant staff must be excluded from working with this medicinal product.
Accidental contact with the skin, eyes or mucous membranes must be treated immediately with copious amounts of water.
Any unused product or waste material should be disposed of in accordance with local requirements for cytotoxic medicinal products.
No incompatibilities have been observed between Yondelis and polyvinylchloride (PVC) and polyethylene (PE) bags and tubing and titanium implantable vascular access systems.
Storage
Store in a refrigerator (2-8°C).
Shelf-Life: Unopened Vials: 24 months.
After dilution and reconstitution, chemical and physical stability has been demonstrated for 30 hrs at 25°C.
From a microbiological point of view, the reconstituted solution should be diluted and used immediately. If not diluted and used immediately, in-use storage times and conditions prior to use of the reconstituted product are the responsibility of the user and would normally not be >24 hrs at 2-8°C, unless reconstitution has taken place in controlled and validated aseptic conditions.
ATC Classification
L01CX01 - trabectedin ; Belongs to the class of other plant alkaloids and natural products. Used in the treatment of cancer.
Presentation/Packing
Vial 1 mg (white to off-white powd for concentrate for solution for infusion) x 1's.
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