Drugs List

Therapeutic Indications

Uses

Combination therapy in relapsed platinum sensitive ovarian cancer
Sarcoma - soft tissue

Treatment of advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide or in patients unsuited to receive these agents.

Treatment in combination with pegylated liposomal doxorubicin (PLD) in patients with relapsed platinum-sensitive ovarian cancer.

Administration

For intravenous infusion.

The use of central venous access is strongly recommended. Administration through a peripheral venous line may be used. However, there is an increased risk of potentially severe injection site reactions.

Contraindications

Albumin less than 2.5g/dl
Alkaline phosphatase greater than 2.5 times the upper limit of normal
Children under 18 years
Creatine phosphokinase (CPK) above 2.5 times the upper limit of normal
Elevated serum transaminases - greater than 2.5 times upper limit of normal
Haemoglobin concentration below 9g/dl
Neutrophil count below 1.5 x 10 to the power of 9 / L at baseline
Platelet count below 100 x 10 to the power of 9/ L
Uncontrolled systemic infection
Breastfeeding
Elevated serum bilirubin
Pregnancy
Renal impairment in combination therapy-creatinine clearance below 60ml/min
Renal impairment in monotherapy - creatinine clearance below 30ml/min

Precautions and Warnings

Cardiomyopathy
Hepatic disorder
Hepatic impairment

Administration of live vaccines is not recommended
Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of oocyte cryopreservation
Give pre-treatment counselling and consideration of sperm cryopreservation
Premedicate with corticosteroids 30 minutes prior to treatment
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of anti-cancer drugs
If extravasation occurs follow local policy & seek expert help immediately
Staff: Not to be handled by pregnant staff
Monitor hepatic function before treatment and regularly during treatment
Monitor renal function before treatment and regularly during treatment
Monitor creatine kinase levels in patients at risk of rhabdomyolysis
Monitor for symptoms of Capillary Leak Syndrome
Monitor full blood count regularly
Monitor LVEF at baseline and periodically during treatment
Monitor patients with cardiac disorders
Monitor serum albumin
Advise patient to report incidences of fever
Advise patient to report symptoms of CLS (e.g oedema, hypotension)
Advise patients to report muscle pain/tenderness/weakness
Reduce dose if grade 3 or 4 toxicities occur
Discontinue if capillary leak syndrome (CLS) develops
Suspend treatment if rhabdomyolysis occurs
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise patient grapefruit products may increase plasma level
Female: Contraception required during and for 3 months after treatment
Male: Contraception required during and for 5 months after treatment
Breastfeeding: Do not breastfeed during & for 3 months after treatment

Prior to re-treatment if severe neutropenia (ANC below 500 cells/cubic millimetre) lasting more than 5 days or associated with fever or infection occurs, a dose reduction is recommended.

Full blood counts including differential and platelet count, bilirubin, alkaline phosphatase, aminotransferases and creatine phosphokinase must be performed at baseline, weekly for the first two cycles then once between cycles.

Rhabdomyolysis has been uncommonly reported, usually in association with myelotoxicity, severe liver function test abnormalities and/or renal or multiorgan failure. Therefore, patients experiencing any of these toxicities should have their CPK closely monitored. If rhabdomyolysis occurs supportive measures should be started (e.g. parenteral hydration, urine alkalinisation and dialysis) and treatment with trabectedin should be discontinued until the patient has fully recovered.

Reversible acute increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) have been reported in most patients. Patients with increases in AST, ALT and alkaline phosphatase between cycles may necessitate dose reduction.

It is recommended to monitor Left Ventricular Ejection Fraction (LVEF) at baseline and periodically; particularly in patients at risk of cardiomyopathy from previous anthracycline exposure or in patients with symptoms of decreasing cardiac function.

Capillary leak syndrome (CLS) has been reported in some patients. If symptoms of CLS develop (e.g oedema or hypotension), assess serum albumin level, as a low serum albumin level may indicate CLS. If CLS is confirmed, discontinue trabectedin and treat CLS.

Pregnancy and Lactation

Pregnancy

Trabectedin is contraindicated in pregnancy.

There is no information from exposed pregnancies. However, based on its mechanism of action it may cause serious birth defects.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Trabectedin is contraindicated in breastfeeding.

It is not known if trabectedin is excreted in milk, a risk to neonates cannot be excluded. The manufacturer contraindicates breastfeeding during and for 3 months after treatment.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acute hepatic injury
Alopecia
Anaemia
Anorexia
Arthralgia
Asthenia
Back pain
Bone marrow toxicity
Capillary leak syndrome
Constipation
Cough
Creatine phosphokinase increased
Decreased appetite
Decreased serum albumin
Dehydration
Diarrhoea
Dizziness
Dysgeusia
Dyspepsia
Dyspnoea
Extravasation
Fatigue
Febrile neutropenia
Flushing
Gamma glutamyl transferase (GGT) increased
Granulocytopenia
Headache
Hepatic pain
Hepatomegaly
Hepatotoxicity
Hyperbilirubinaemia
Hyperpigmentation of skin
Hypersensitivity reactions
Hypokalaemia
Hypotension
Increase in alkaline phosphatase
Increase in serum ALT/AST
Infections
Infertility
Injection site reactions
Insomnia
Jaundice
Leukopenia
Mucosal inflammation
Multiorgan failure
Musculoskeletal pain
Myalgia
Nausea
Neutropenia
Oedema
Palmar-Plantar Erythrodysaesthesia syndrome
Pancytopenia
Paraesthesia
Peripheral neuropathy
Peripheral oedema
Pulmonary embolism
Pulmonary oedema
Pyrexia
Rash
Renal failure
Rhabdomyolysis
Sepsis
Serum creatinine increased
Stomatitis
Syncope
Thrombocytopenia
Upper abdominal pain
Ventricular dysfunction
Vomiting
Weight loss

Presentation

Infusions of trabectedin.

Drugs List

Therapeutic Indications

Uses

Combination therapy in relapsed platinum sensitive ovarian cancer
Sarcoma - soft tissue

Treatment of advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide or in patients unsuited to receive these agents.

Treatment in combination with pegylated liposomal doxorubicin (PLD) in patients with relapsed platinum-sensitive ovarian cancer.

Dosage

Due to the complexity and specialist nature of dosage regimens for the treatment of malignant disease, specific dosing information on this agent is not included.

Doses may vary significantly if this agent is used as monotherapy or different combinations.

When using this agent, specialist literature, national guidelines, cancer networks protocols and Trust chemotherapy protocols should be consulted.

Additional Dosage Information

Administration

For intravenous infusion.

The use of central venous access is strongly recommended. Administration through a peripheral venous line may be used. However, there is an increased risk of potentially severe injection site reactions.

Contraindications

Albumin less than 2.5g/dl
Alkaline phosphatase greater than 2.5 times the upper limit of normal
Children under 18 years
Creatine phosphokinase (CPK) above 2.5 times the upper limit of normal
Elevated serum transaminases - greater than 2.5 times upper limit of normal
Haemoglobin concentration below 9g/dl
Neutrophil count below 1.5 x 10 to the power of 9 / L at baseline
Platelet count below 100 x 10 to the power of 9/ L
Uncontrolled systemic infection
Breastfeeding
Elevated serum bilirubin
Pregnancy
Renal impairment in combination therapy-creatinine clearance below 60ml/min
Renal impairment in monotherapy - creatinine clearance below 30ml/min

Precautions and Warnings

Cardiomyopathy
Hepatic disorder
Hepatic impairment

Administration of live vaccines is not recommended
Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of oocyte cryopreservation
Give pre-treatment counselling and consideration of sperm cryopreservation
Premedicate with corticosteroids 30 minutes prior to treatment
Treatment to be initiated and supervised by a specialist
Consult local policy on the safe use of anti-cancer drugs
If extravasation occurs follow local policy & seek expert help immediately
Staff: Not to be handled by pregnant staff
Monitor hepatic function before treatment and regularly during treatment
Monitor renal function before treatment and regularly during treatment
Monitor creatine kinase levels in patients at risk of rhabdomyolysis
Monitor for symptoms of Capillary Leak Syndrome
Monitor full blood count regularly
Monitor LVEF at baseline and periodically during treatment
Monitor patients with cardiac disorders
Monitor serum albumin
Advise patient to report incidences of fever
Advise patient to report symptoms of CLS (e.g oedema, hypotension)
Advise patients to report muscle pain/tenderness/weakness
Reduce dose if grade 3 or 4 toxicities occur
Discontinue if capillary leak syndrome (CLS) develops
Suspend treatment if rhabdomyolysis occurs
Advise patient not to take St John's wort concurrently
Advise patient to avoid alcohol during treatment
Advise patient grapefruit products may increase plasma level
Female: Contraception required during and for 3 months after treatment
Male: Contraception required during and for 5 months after treatment
Breastfeeding: Do not breastfeed during & for 3 months after treatment

Prior to re-treatment if severe neutropenia (ANC below 500 cells/cubic millimetre) lasting more than 5 days or associated with fever or infection occurs, a dose reduction is recommended.

Full blood counts including differential and platelet count, bilirubin, alkaline phosphatase, aminotransferases and creatine phosphokinase must be performed at baseline, weekly for the first two cycles then once between cycles.

Rhabdomyolysis has been uncommonly reported, usually in association with myelotoxicity, severe liver function test abnormalities and/or renal or multiorgan failure. Therefore, patients experiencing any of these toxicities should have their CPK closely monitored. If rhabdomyolysis occurs supportive measures should be started (e.g. parenteral hydration, urine alkalinisation and dialysis) and treatment with trabectedin should be discontinued until the patient has fully recovered.

Reversible acute increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) have been reported in most patients. Patients with increases in AST, ALT and alkaline phosphatase between cycles may necessitate dose reduction.

It is recommended to monitor Left Ventricular Ejection Fraction (LVEF) at baseline and periodically; particularly in patients at risk of cardiomyopathy from previous anthracycline exposure or in patients with symptoms of decreasing cardiac function.

Capillary leak syndrome (CLS) has been reported in some patients. If symptoms of CLS develop (e.g oedema or hypotension), assess serum albumin level, as a low serum albumin level may indicate CLS. If CLS is confirmed, discontinue trabectedin and treat CLS.

Pregnancy and Lactation

Pregnancy

Trabectedin is contraindicated in pregnancy.

There is no information from exposed pregnancies. However, based on its mechanism of action it may cause serious birth defects.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Trabectedin is contraindicated in breastfeeding.

It is not known if trabectedin is excreted in milk, a risk to neonates cannot be excluded. The manufacturer contraindicates breastfeeding during and for 3 months after treatment.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Acute hepatic injury
Alopecia
Anaemia
Anorexia
Arthralgia
Asthenia
Back pain
Bone marrow toxicity
Capillary leak syndrome
Constipation
Cough
Creatine phosphokinase increased
Decreased appetite
Decreased serum albumin
Dehydration
Diarrhoea
Dizziness
Dysgeusia
Dyspepsia
Dyspnoea
Extravasation
Fatigue
Febrile neutropenia
Flushing
Gamma glutamyl transferase (GGT) increased
Granulocytopenia
Headache
Hepatic pain
Hepatomegaly
Hepatotoxicity
Hyperbilirubinaemia
Hyperpigmentation of skin
Hypersensitivity reactions
Hypokalaemia
Hypotension
Increase in alkaline phosphatase
Increase in serum ALT/AST
Infections
Infertility
Injection site reactions
Insomnia
Jaundice
Leukopenia
Mucosal inflammation
Multiorgan failure
Musculoskeletal pain
Myalgia
Nausea
Neutropenia
Oedema
Palmar-Plantar Erythrodysaesthesia syndrome
Pancytopenia
Paraesthesia
Peripheral neuropathy
Peripheral oedema
Pulmonary embolism
Pulmonary oedema
Pyrexia
Rash
Renal failure
Rhabdomyolysis
Sepsis
Serum creatinine increased
Stomatitis
Syncope
Thrombocytopenia
Upper abdominal pain
Ventricular dysfunction
Vomiting
Weight loss

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: March 2015

Reference Sources

Joint Formulary Committee. British National Formulary(online) London: BMJ Group and Pharmaceutical Press. Accessed on 17 February 2015.

Martindale: The Complete Drug Reference (online) London: Brayfield A (ed). Pharmaceutical Press. Accessed on 17 February 2015.

Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications. Accessed on 17 February 2015.

Summary of Product Characteristics: Yondelis 0.25 mg powder for concentrate for solution for infusion/Yondelis 1 mg powder for concentrate for solution for infusion. Pharma Mar S.A. Revised July 2016.