Metastatic adenocarcinoma of the pancreas in patients
who have progressed following gemcitabine based
therapy (in combination with fluorouracil and
leucovorin) (specialist use only)
▶ BY INTRAVENOUS INFUSION USING LIPID FORMULATION
▶ Adult: (consult product literature or local protocols)
MHRA/CHM ADVICE: ONIVYDE ® (IRINOTECAN, LIPOSOMAL
FORMULATIONS): REPORTS OF SERIOUS AND FATAL
THROMBOEMBOLIC EVENTS (MARCH 2019)
Onivyde ® has been associated with reports of serious
thromboembolic events, such as pulmonary embolism,
venous thrombosis, and arterial thromboembolism.
Healthcare professionals are advised to obtain a
thorough medical history to identify patients with
multiple risk factors. Patients should be advised to seek
medical advice immediately if signs or symptoms of
thromboembolism occur, such as sudden pain and
swelling in a leg or an arm, sudden onset of coughing,
chest pain or difficulty breathing.
l CONTRA-INDICATIONS Bowel obstruction . chronic
l CAUTIONS Raised plasma-bilirubin concentration .risk
factors for cardiac disease .risk factors for pulmonary
toxicity . underweight patients—increased risk of adverse
l INTERACTIONS → Appendix 1: irinotecan
syndrome . constipation . decreased leucocytes . diarrhoea
▶ Uncommon Hypersensitivity . hypoxia . nail discolouration . skin reactions
cramps . paraesthesia . speech disorder. ulcerative colitis
l CONCEPTION AND CONTRACEPTION For conventional
formulations, manufacturer advises effective
contraception during treatment and for up to 1 month
after treatment in women of child-bearing potential, and
up to 3 months after treatment in men. For liposomal
formulations, manufacturer advises effective
contraception during treatment and for up to 1 month
after treatment in women of child-bearing potential, and
up to 4 months after treatment in men.
l PREGNANCY Manufacturer advises avoid unless
essential—toxicity in animal studies. See also Pregnancy
and reproductive function in Cytotoxic drugs p. 888.
l BREAST FEEDING For conventional formulations,
manufacturer advises avoid. For liposomal formulations,
manufacturer advises avoid until one month after the last
dose—no information available.
l HEPATIC IMPAIRMENT For conventional formulations,
manufacturer advises caution if bilirubin concentration
1.5–3 times the upper limit of normal (risk of decreased
clearance)—monitor liver function at baseline and before
each cycle; avoid if bilirubin concentration greater than
3 times the upper limit of normal (no information available
for combination therapy). For liposomal formulations,
manufacturer advises caution; avoid if bilirubin greater
than 2 mg/dL, or if transaminases are greater than
2.5 times the upper limit of normal, or greater than 5 times
the upper limit of normal if liver metastasis present
(limited information available).
Dose adjustments For conventional formulations,
manufacturer advises dose reduction—consult product
l RENAL IMPAIRMENT For conventional formulations,
manufacturer advises avoid—no information available. For
liposomal formulations, manufacturer advises avoid in
severe impairment—no information available.
l MONITORING REQUIREMENTS Manufacturer advises
monitor for respiratory symptoms in patients with risk
factors for interstitial lung disease before and during
treatment; monitor complete blood count weekly during
l PRESCRIBING AND DISPENSING INFORMATION Irinotecan is
available as both conventional and liposomal formulations.
Manufacturers advise that the different formulations vary
in their licensed indications, pharmacokinetics, dosage
and administration, and are not interchangeable.
Driving and skilled tasks Manufacturer advises patients and
carers should be counselled on the effects on driving and
performance of skilled tasks—increased risk of dizziness
and visual disturbances within 24 hours of administration.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Irinotecan, oxaliplatin, and raltitrexed for advanced colorectal
cancer (August 2005) NICE TA93
A combination of fluorouracil and folinic acid with either
irinotecan or oxaliplatin are options for first-line
treatment for advanced colorectal cancer.
Irinotecan alone or fluorouracil and folinic acid with
oxaliplatin are options for patients who require further
▶ Pegylated liposomal irinotecan for treating pancreatic cancer
after gemcitabine (April 2017) NICE TA440
Pegylated liposomal irinotecan, in combination with
fluorouracil and leucovorin, is not recommended for
treating metastatic adenocarcinoma of the pancreas in
adults whose disease has progressed after gemcitabinebased therapy.
Patients whose treatment was started within the NHS
before this guidance was published should have the option
to continue treatment, without change to their funding
arrangements, until they and their clinician consider it
www.nice.org.uk/guidance/TA440
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (March
2017) that liposomal irinotecan (Onivyde ®) is not
recommended for use within NHS Scotland for the
treatment of metastatic adenocarcinoma of the pancreas,
in combination with fluorouracil and leucovorin (folinic
acid), in patients who have progressed following
gemcitabine based therapy as there was insufficient
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
ELECTROLYTES: May contain Sodium
▶ Irinotecan hydrochloride (Non-proprietary)
Irinotecan hydrochloride trihydrate 20 mg per 1 ml Irinotecan
500mg/25ml concentrate for solution for infusion vials | 1 vial P £393.75–£730.82 (Hospital only)
BNF 78 Cytotoxic responsive malignancy 927
Immune system and malignant disease
Irinotecan 100mg/5ml concentrate for solution for infusion vials |
1 vial P £96.25–£130.00 (Hospital only) | 1 vial P £120.25–
Irinotecan hydrochloride trihydrate 20 mg per 1 ml Campto
100mg/5ml concentrate for solution for infusion vials | 1 vial P £130.00 (Hospital only)
Campto 40mg/2ml concentrate for solution for infusion vials |
1 vial P £53.00 (Hospital only)
Campto 300mg/15ml concentrate for solution for infusion vials | 1 vial P £390.00 (Hospital only)
▶ Onivyde (Servier Laboratories Ltd)
Irinotecan hydrochloride trihydrate liposomal pegylated 5 mg
per 1 ml Onivyde 50mg/10ml concentrate for solution for infusion
vials | 1 vial P £615.35 (Hospital only)
l DRUG ACTION Topotecan inhibits topoisomerase I, an
enzyme involved in DNA replication.
Metastatic ovarian cancer when first-line or subsequent
treatment has failed | Treatment of recurrent carcinoma
of the cervix, after radiotherapy, and for patients with
stage IVB disease (in combination with cisplatin)
▶ Adult: (consult product literature or local protocols)
Relapsed small-cell lung cancer when retreatment with
the first-line regimen is considered inappropriate
▶ BY INTRAVENOUS INFUSION, OR BY MOUTH
▶ Adult: (consult product literature or local protocols)
RISKS OF INCORRECT DOSING OF ORAL ANTI-CANCER MEDICINES
l INTERACTIONS → Appendix 1: topotecan
▶ Common or very common Alopecia . anaemia . appetite
▶ Rare or very rare Angioedema . interstitial lung disease
▶ Frequency not known Bone marrow depression (doselimiting). haemorrhage
l CONCEPTION AND CONTRACEPTION Contraceptive advice
required, see Pregnancy and reproductive function in
l PREGNANCY Avoid (teratogenicity and fetal loss in animal
studies). See also Pregnancy and reproductive function in
l BREAST FEEDING Discontinue breast-feeding.
l HEPATIC IMPAIRMENT Manufacturer advises avoid in
severe impairment (limited information available).
l RENAL IMPAIRMENT Avoid infusion if creatinine clearance
less than 20 mL/minute. Avoid oral route if creatinine
clearance less than 60 mL/minute.
l NATIONAL FUNDING/ACCESS DECISIONS
▶ Topotecan for the treatment of recurrent and stage IVB
cervical cancer (October 2009) NICE TA183
Topotecan in combination with cisplatin is recommended
as a treatment option for recurrent or stage IVB cervical
cancer in patients who have not previously received
▶ Topotecan for the treatment of relapsed small-cell lung cancer
Oral topotecan is recommended as an option for treatment
appropriate, and the combination of cyclophosphamide,
doxorubicin and vincristine is contra-indicated.
Intravenous topotecan is not recommended for people
with relapsed small-cell lung cancer.
▶ Topotecan, pegylated liposomal doxorubicin hydrochloride,
paclitaxel, trabectedin and gemcitabine for treating recurrent
ovarian cancer (April 2016) NICE TA389
Topotecan is not recommended for treating first
recurrence of platinum-sensitive ovarian cancer, recurrent
platinum-resistant ovarian cancer, or platinum-refractory
Patients currently receiving topotecan should have the
option to continue their treatment until they or their
clinician consider it appropriate to stop.
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (November
2007) that topotecan (Hycamtin ®) is accepted for restricted
use in combination with cisplatin for treatment of
recurrent carcinoma of the cervix after radiotherapy and
for stage IVB disease; it is restricted to patients who have
not previously received cisplatin treatment.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
Topotecan (as Topotecan hydrochloride) 1 mg per 1 ml Topotecan
4mg/4ml concentrate for solution for infusion vials | 5 vial P £1,453.10 (Hospital only)
Powder for solution for infusion
▶ Hycamtin (Novartis Pharmaceuticals UK Ltd)
Topotecan (as Topotecan hydrochloride) 1 mg Hycamtin 1mg
powder for concentrate for solution for infusion vials | 1 vial P £97.65
Topotecan (as Topotecan hydrochloride) 4 mg Hycamtin 4mg
powder for concentrate for solution for infusion vials | 1 vial P £348.76
Topotecan (as Topotecan hydrochloride) 4 mg Potactasol 4mg
powder for concentrate for solution for infusion vials | 1 vial P £290.00 (Hospital only)
CAUTIONARY AND ADVISORY LABELS 25
▶ Hycamtin (Novartis Pharmaceuticals UK Ltd)
Topotecan (as Topotecan hydrochloride)
250 microgram Hycamtin 0.25mg capsules | 10 capsule P £75.00
Topotecan (as Topotecan hydrochloride) 1 mg Hycamtin 1mg
capsules | 10 capsule P £360.00
928 Cytotoxic responsive malignancy BNF 78
Immune system and malignant disease
ANTINEOPLASTIC DRUGS › VINCA ALKALOIDS
Variety of cancers including leukaemias, lymphomas, and
some solid tumours (e.g. breast and lung cancer)
▶ Adult: (consult product literature)
Vinblastine is for intravenous administration only.
Inadvertent intrathecal administration can cause severe
neurotoxicity, which is usually fatal.
The National Patient Safety Agency has advised
(August 2008) that adult and teenage patients treated in
an adult or adolescent unit should receive their vinca
alkaloid dose in a 50 mL minibag. Teenagers and children
treated in a child unit may receive their vinca alkaloid
CONTRA-INDICATIONS, FURTHER INFORMATION
Intrathecal injection contra-indicated.
l CAUTIONS Caution in handling—irritant to tissues
l INTERACTIONS → Appendix 1: vinca alkaloids
▶ Rare or very rare Hearing impairment. nerve disorders . vestibular damage
▶ Frequency not known Abdominal pain . acute respiratory
l CONCEPTION AND CONTRACEPTION Contraceptive advice
required, see Pregnancy and reproductive function in
l PREGNANCY Avoid (limited experience suggests fetal
harm; teratogenic in animal studies). See also Pregnancy
and reproductive function in Cytotoxic drugs p. 888.
l BREAST FEEDING Discontinue breast-feeding.
l HEPATIC IMPAIRMENT Manufacturer advises caution in
significantly impaired hepatic or biliary function.
Dose adjustments Manufacturer advises consider initial
dose reduction in significantly impaired hepatic or biliary
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Vinblastine sulfate (Non-proprietary)
Vinblastine sulfate 1 mg per 1 ml Vinblastine 10mg/10ml solution
for injection vials | 5 vial P £85.00 (Hospital only)
Variety of cancers including leukaemias, lymphomas, and
some solid tumours (e.g. breast and lung cancer)
▶ Adult: (consult local protocol)
Vincristine injections are for intravenous
administration only. Inadvertent intrathecal
administration can cause severe neurotoxicity, which is
The National Patient Safety Agency has advised
(August 2008) that adult and teenage patients treated in
an adult or adolescent unit should receive their vinca
alkaloid dose in a 50 mL minibag. Teenagers and children
treated in a child unit may receive their vinca alkaloid
CONTRA-INDICATIONS, FURTHER INFORMATION
Intrathecal injection contra-indicated.
l CAUTIONS Caution in handling—irritant to tissues . neuromuscular disease
l INTERACTIONS → Appendix 1: vinca alkaloids
▶ Rare or very rare Hypersensitivity .rash . SIADH
absent.renal disorder. secondary malignancy . sensation
abnormal . sepsis .throat pain .thrombocytopenia . urinary
disorders . vertigo . vestibular damage . vision loss . vomiting . weight decreased
SIDE-EFFECTS, FURTHER INFORMATION Bronchospasm
Severe bronchospasm following administration is more
common when used in combination with mitomycin-C.
Neurotoxicity Sensory and motor neuropathies are
common and are cumulative. Manufacturer advises
monitoring patients for symptoms of neuropathy, such as
hypoesthesia, hyperesthesia, paresthesia, hyporeflexia,
areflexia, neuralgia, jaw pain, decreased vibratory sense,
cranial neuropathy, ileus, burning sensation, arthralgia,
myalgia, muscle spasm, or weakness, both before and
during treatment—requires dose reduction, treatment
interruption or treatment discontinuation, depending on
Motor weakness can also occur and dose reduction or
discontinuation of therapy may be appropriate if motor
weakness increases. Recovery from neurotoxic effects is
l CONCEPTION AND CONTRACEPTION Contraceptive advice
required, see Pregnancy and reproductive function in
l PREGNANCY Avoid (teratogenicity and fetal loss in animal
studies). See also Pregnancy and reproductive function in
l BREAST FEEDING Discontinue breast-feeding.
l HEPATIC IMPAIRMENT Manufacturer advises caution.
Dose adjustments Manufacturer advises dose reduction.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug.
▶ Vincristine sulfate (Non-proprietary)
Vincristine sulfate 1 mg per 1 ml Vincristine 1mg/1ml solution for
injection vials | 1 vial P £13.47 (Hospital only) | 5 vial P £67.35 (Hospital only)
Vincristine 2mg/2ml solution for injection vials | 1 vial P £26.66
(Hospital only) | 5 vial P £133.30 (Hospital only)
Vincristine 5mg/5ml solution for injection vials | 5 vial P £329.50
BNF 78 Cytotoxic responsive malignancy 929
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