Drugs List

Therapeutic Indications

Uses

Locally advanced or metastatic adenocarcinoma of pancreas

Metastatic adenocarcinoma of the pancreas, in combination with 5-fluorouracil and leucovorin in adult patients who have progressed following gemcitabine therapy.

Administration

Dilute before use and give by intravenous infusion over 90 minutes.

Contraindications

Children under 18 years
Elevated serum transaminases - greater than 2.5 times upper limit of normal
Neutrophil count below 1.5 x 10 to the power of 9 / L
Platelet count below 100 x 10 to the power of 9/ L
Breastfeeding
Chronic inflammatory bowel disease
Gastrointestinal obstruction
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Serum bilirubin above 2 times upper limit of normal
Serum transaminases above 5x ULN with concurrent liver metastasis
Severe myelosuppression

Precautions and Warnings

Asian ancestry
Concurrent radiotherapy
History of abdominal radiation
History of Whipple procedure (pancreaticoduodenectomy)
Predisposition to thromboembolic disease
Restricted sodium intake
UGT1A1*28 homozygous genotype
Underweight patients
Gilbert's syndrome
Respiratory disease

Administration of live vaccines is not recommended
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Different formulations are not bioequivalent
Consult local policy on the safe use of anti-cancer drugs
Febrile neutropenia should be treated with broad spectrum IV antibiotics
Staff: Not to be handled by pregnant staff
Monitor for signs and symptoms of interstitial lung disease
Monitor full blood count regularly
Advise patient of thromboembolic symptoms and to report them if they occur
Advise patient to inform physician if/when (delayed) diarrhoea occurs
Advise patient to report any symptoms of interstitial lung disease
Advise patient to report symptoms of infection immediately
Antibody response to vaccines may be reduced
Cholinergic syndrome should be treated with subcutaneous atropine
Consider dose reduction for subsequent doses if severe diarrhoea occurs
Diarrhoea to be managed with electrolyte/fluids+high dose loperamide
Prophylactic antiemetic recommended before each dose
Discontinue if evidence of interstitial lung disease
Discontinue if hypersensitivity reactions occur
Interrupt treatment if febrile neutropenia occurs
Suspend treatment if interstitial lung disease is suspected
Suspend treatment if neutrophil count is less than 1,500/cubic mm
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Female: Contraception required during and for 1 month after treatment
Male: Use of condoms required during and for 4 months after treatment
Breastfeeding: Do not breastfeed during & for 1 month after treatment
Advise on measures to take if diarrhoea occurs
Advise patients on the risk of neutropenia and the significance of fever

Risk factors associated with the development of interstitial pulmonary (presenting as pulmonary infiltrates) disease include the use of pneumotoxic drugs, radiation therapy and colony stimulating factors. Patients with risk factors should be monitored for respiratory symptoms before and during therapy.

Diarrhoea
Diarrhoea must be treated immediately and appropriately at its occurrence, as there is a risk that it can become life threatening. Patients who are concomitantly neutropenic are at particular risk.

If early diarrhoea occurs therapeutic and prophylactic atropine should be considered unless contraindicated.
Patients should be made aware of the risk of delayed diarrhoea occurring more than 24 hours after the administration of irinotecan and at any time before the next administration.

Patients should be advised to inform their physician of the occurrence of diarrhoea. Large amounts of fluid containing electrolytes and the appropriate antidiarrhoeal therapy should be taken as soon as diarrhoea occurs, the appropriate treatment should be available for immediate administration at the occurrence of diarrhoea.

If diarrhoea persists despite 24 hours of loperamide treatment, addition of an oral antibiotic should be considered. Loperamide should not be administered for more than 48 hours (risk of paralytic ileus).

Pregnancy and Lactation

Pregnancy

Irinotecan is contraindicated in pregnancy.

However, Briggs concludes that if a woman requires irinotecan and informed consent is obtained, treatment should not be withheld because of pregnancy. If an inadvertent pregnancy occurs, the woman should be advised of the possible risk for severe adverse effects in the embryo and foetus.

There is limited information on the use of irinotecan in pregnant women, however it has been shown to be embryotoxic, foetotoxic and teratogenic in rabbits and rats.

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

Irinotecan is contraindicated in breastfeeding.

It is not known if irinotecan is excreted in human breast milk but it has been detected in the milk of lactating rats. Due to the potential for serious adverse reactions in nursing infants, women receiving this drug should not breastfeed.

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
Abnormal INR
Acute cholinergic syndrome
Acute renal failure
Alanine aminotransferase increased
Alopecia
Anaemia
Aspartate aminotransferase increased
Asthenia
Biliary sepsis
Candidiasis (mouth or throat)
Colitis
Decreased appetite
Deep vein thrombosis (DVT)
Dehydration
Diarrhoea
Dizziness
Dysgeusia
Dysphonia
Dyspnoea
Embolism
Fatigue
Febrile neutropenia
Gastro-enteritis
Haemorrhoids
Hypersensitivity reactions
Hypoalbuminaemia
Hypoglycaemia
Hypokalaemia
Hypomagnesaemia
Hyponatraemia
Hypophosphataemia
Hypotension
Hypoxia
Infusion related reaction
Insomnia
Interstitial lung disease
Leukopenia
Lymphopenia
Maculopapular rash
Mucosal inflammation
Nausea
Neutropenia
Oedema
Oesophagitis
Peripheral oedema
Pigmentation of nails
Pneumonia
Proctitis
Pulmonary embolism
Pulmonary toxicity
Pyrexia
Sepsis
Septic shock
Serum bilirubin increased
Stomatitis
Thrombocytopenia
Thrombosis
Vomiting
Weight loss

Presentation

Concentrate for solution for infusion containing irinotecan sucrosofate in a pegylated liposomal formulation

The concentrate has a pH of 7.2 and an osmolarity of 295 mOsm/kg

Drugs List

Therapeutic Indications

Uses

Locally advanced or metastatic adenocarcinoma of pancreas

Metastatic adenocarcinoma of the pancreas, in combination with 5-fluorouracil and leucovorin in adult patients who have progressed following gemcitabine therapy.

Dosage

Whilst the doses stated below are those recommended by the manufacturer, local cancer network protocols for the relevant indication should be consulted.

Liposomal irinotecan should not be used interchangeably with other formulations of irinotecan.

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

Adults

Elderly

Patients with Renal Impairment

Additional Dosage Information

Administration

Dilute before use and give by intravenous infusion over 90 minutes.

Contraindications

Children under 18 years
Elevated serum transaminases - greater than 2.5 times upper limit of normal
Neutrophil count below 1.5 x 10 to the power of 9 / L
Platelet count below 100 x 10 to the power of 9/ L
Breastfeeding
Chronic inflammatory bowel disease
Gastrointestinal obstruction
Pregnancy
Renal impairment - creatinine clearance below 30 ml/minute
Serum bilirubin above 2 times upper limit of normal
Serum transaminases above 5x ULN with concurrent liver metastasis
Severe myelosuppression

Precautions and Warnings

Asian ancestry
Concurrent radiotherapy
History of abdominal radiation
History of Whipple procedure (pancreaticoduodenectomy)
Predisposition to thromboembolic disease
Restricted sodium intake
UGT1A1*28 homozygous genotype
Underweight patients
Gilbert's syndrome
Respiratory disease

Administration of live vaccines is not recommended
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Treatment to be initiated and supervised by a specialist
Different formulations are not bioequivalent
Consult local policy on the safe use of anti-cancer drugs
Febrile neutropenia should be treated with broad spectrum IV antibiotics
Staff: Not to be handled by pregnant staff
Monitor for signs and symptoms of interstitial lung disease
Monitor full blood count regularly
Advise patient of thromboembolic symptoms and to report them if they occur
Advise patient to inform physician if/when (delayed) diarrhoea occurs
Advise patient to report any symptoms of interstitial lung disease
Advise patient to report symptoms of infection immediately
Antibody response to vaccines may be reduced
Cholinergic syndrome should be treated with subcutaneous atropine
Consider dose reduction for subsequent doses if severe diarrhoea occurs
Diarrhoea to be managed with electrolyte/fluids+high dose loperamide
Prophylactic antiemetic recommended before each dose
Discontinue if evidence of interstitial lung disease
Discontinue if hypersensitivity reactions occur
Interrupt treatment if febrile neutropenia occurs
Suspend treatment if interstitial lung disease is suspected
Suspend treatment if neutrophil count is less than 1,500/cubic mm
Advise patient not to take St John's wort concurrently
Advise patient grapefruit products may increase plasma level
Female: Contraception required during and for 1 month after treatment
Male: Use of condoms required during and for 4 months after treatment
Breastfeeding: Do not breastfeed during & for 1 month after treatment
Advise on measures to take if diarrhoea occurs
Advise patients on the risk of neutropenia and the significance of fever

Risk factors associated with the development of interstitial pulmonary (presenting as pulmonary infiltrates) disease include the use of pneumotoxic drugs, radiation therapy and colony stimulating factors. Patients with risk factors should be monitored for respiratory symptoms before and during therapy.

Diarrhoea
Diarrhoea must be treated immediately and appropriately at its occurrence, as there is a risk that it can become life threatening. Patients who are concomitantly neutropenic are at particular risk.

If early diarrhoea occurs therapeutic and prophylactic atropine should be considered unless contraindicated.
Patients should be made aware of the risk of delayed diarrhoea occurring more than 24 hours after the administration of irinotecan and at any time before the next administration.

Patients should be advised to inform their physician of the occurrence of diarrhoea. Large amounts of fluid containing electrolytes and the appropriate antidiarrhoeal therapy should be taken as soon as diarrhoea occurs, the appropriate treatment should be available for immediate administration at the occurrence of diarrhoea.

If diarrhoea persists despite 24 hours of loperamide treatment, addition of an oral antibiotic should be considered. Loperamide should not be administered for more than 48 hours (risk of paralytic ileus).

Pregnancy and Lactation

Pregnancy

Irinotecan is contraindicated in pregnancy.

However, Briggs concludes that if a woman requires irinotecan and informed consent is obtained, treatment should not be withheld because of pregnancy. If an inadvertent pregnancy occurs, the woman should be advised of the possible risk for severe adverse effects in the embryo and foetus.

There is limited information on the use of irinotecan in pregnant women, however it has been shown to be embryotoxic, foetotoxic and teratogenic in rabbits and rats.

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

Irinotecan is contraindicated in breastfeeding.

It is not known if irinotecan is excreted in human breast milk but it has been detected in the milk of lactating rats. Due to the potential for serious adverse reactions in nursing infants, women receiving this drug should not breastfeed.

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
Abnormal INR
Acute cholinergic syndrome
Acute renal failure
Alanine aminotransferase increased
Alopecia
Anaemia
Aspartate aminotransferase increased
Asthenia
Biliary sepsis
Candidiasis (mouth or throat)
Colitis
Decreased appetite
Deep vein thrombosis (DVT)
Dehydration
Diarrhoea
Dizziness
Dysgeusia
Dysphonia
Dyspnoea
Embolism
Fatigue
Febrile neutropenia
Gastro-enteritis
Haemorrhoids
Hypersensitivity reactions
Hypoalbuminaemia
Hypoglycaemia
Hypokalaemia
Hypomagnesaemia
Hyponatraemia
Hypophosphataemia
Hypotension
Hypoxia
Infusion related reaction
Insomnia
Interstitial lung disease
Leukopenia
Lymphopenia
Maculopapular rash
Mucosal inflammation
Nausea
Neutropenia
Oedema
Oesophagitis
Peripheral oedema
Pigmentation of nails
Pneumonia
Proctitis
Pulmonary embolism
Pulmonary toxicity
Pyrexia
Sepsis
Septic shock
Serum bilirubin increased
Stomatitis
Thrombocytopenia
Thrombosis
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 2017

Reference Sources

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Onivyde concentrate for solution for infusion. Baxalta UK Ltd. October 2016.

The Renal Drug Handbook. Fourth Edition (2014) ed. Ashley, C and Dunleavy, A, Radcliffe Publishing Ltd, London.