Irinotecan Hydrochloride Trihydrate

Registered South African indications:

• Colorectal cancer

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Chronic inflammatory bowel disease and/or bowel obstruction
• Severe bone marrow failure
• WHO performance status > 2
• Bilirubin > 3 times the upper limit of normal
• Coadministration with St John's Wort
• Yellow fever vaccine

Cautions

• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Previous abdominal/pelvic radiotherapy
• Baseline serum total bilirubin levels of 1mg/dL
• Baseline hyperleucocytosis
• Asthma
• Risk factors for interstitial pulmonary disease
• Multiple risk factors for thromboembolic events
• Extensive prior irradiation
• Risk factors for cardiovascular disease
• Previous cytotoxic chemotherapy
• Patients of childbearing potential
• Fructose intolerance
• Patients with an increased risk of diarrhoea
• History of febrile neutropenia
• History of chemotherapy-induced severe nausea and vomiting
• Vaccination with a live attenuated vaccine

Forms avail. in SA and covered in this monograph: inj

Used for the treatment of

Advanced colorectal cancer (additional agent required)

Consult specialist for dosages and regimens

Not established for use in children

Pregnancy

• Contraindicated
• There is no information on the use of irinotecan in pregnant women
• Irinotecan has been shown to be embryotoxic and teratogenic in animals
• Therefore, based on results from animal studies and the mechanism of action of irinotecan, irinotecan should not be used during pregnancy unless clearly necessary

Breastfeeding

• Caution; not recommended
• In lactating rats, 14C-irinotecan was detected in milk
• It is not known whether irinotecan is excreted in human milk. Consequently, because of the potential for adverse reactions in nursing infants, breastfeeding must be discontinued for the duration of irinotecan therapy

Fertility

• There are no human data on the effect of irinotecan on fertility 
• In animals, adverse effects of irinotecan on the fertility of offspring has been documented
• Women of childbearing potential and men have to use effective contraception during and up to 1 month and 3 months after treatment respectively

Renal Impairment

• Caution; no information available

Hepatic Impairment

• Caution; dose adjustment recommended

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Central Nervous System Disorders

• Confusion
• Cholinergic syndrome
• Transient speech disorders
• Paraesthesia
• Headache
• Syncope
• Asthenia

Cardiovascular Disorders

• Hypertension
• Cardiocirculatory failure
• Cardiovascular disorders 
• Cardiac arrest
• Myocardial infarction
• Myocardial ischaemia
• Bradycardia
• Hypotension
• Flushing
• Thromboembolic events 
• Cerebral infarction
• Cerebrovascular accident
• Deep thrombophlebitis
• Embolus of the lower extremity
• Pulmonary embolus
• Thrombophlebitis
• Thrombosis
• Sudden death
• Peripheral vascular disorder

Respiratory Disorders

• Interstitial pulmonary disease 
• Pulmonary infiltrates
• Dyspnoea
• Hiccups

Gastrointestinal Disorders

• Pseudomembranous colitis
• Diarrhoea
• Nausea and vomiting
• Abdominal pain
• Constipation
• Intestinal obstruction
• Ileus
• Megacolon
• Gastrointestinal haemorrhage
• Colitis
• Typhlitis
• Ischemic and ulcerative colitis
• Gastrointestinal bleeding
• Elevation in pancreatic enzymes
• Intestinal perforation
• Gastrointestinal monilia

Hepatobiliary Disorders

• Increased blood creatinine 
• Increased transaminases 
• Increased bilirubin
• Increased blood alkaline phosphatase
• Increases in serum levels of transaminases 

Genitourinary Disorders

• Renal impairment 
• Acute renal failure
• Renal insufficiency
• Urinary tract infection
• Breast pain

Endocrine and Metabolic Disorders

• Decreased appetite
• Dehydration
• Hypovolaemia
• Hypomagnesaemia
• Tumour lysis syndrome
• Hypokalaemia
• Hyponatraemia

Musculoskeletal Disorders

• Muscular contraction or cramps
• Abnormal gait

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Skin reactions
• Rash
• Mucosal inflammation
• Infusion site reactions
• Extravasation

Immune, Blood and Lymphatic System Disorders

• Neutropenia
• Anaemia
• Thrombocytopenia
• Febrile neutropenia
• Peripheral thrombocytopenia with antiplatelet antibodies
• Hypersensitivity reaction
• Anaphylactic reaction
• Infection
• Sepsis
• Pyrexia

• Live or live attenuated vaccines
• CYP3A4 inhibitor
• CYP3A4 inducer
• Neuromuscular blockings
• Atazanavir sulfate
• Anticoagulants 
• Ciclosporine
• Tacrolimus
• Phenytoin
• Inactivated vaccine (polio)

• Full blood count with differential
• Hepatic function
• International normalised ratio
• Electrolytes

Interactions with anticoagulants

• The use of anticoagulants is common due to the increased risk of thrombotic events in tumoural diseases. If vitamin K anatagonist anticoagulants are indicated, an increased frequency in the monitoring of INR (International Normalised Ratio) is required due to their narrow therapeutic index, the high intra-individual variability of blood thrombogenicity and the possibility of interaction between oral anticoagulants and anticancer chemotherapy

Irinotecan is a semi-synthetic derivative of camptothecin. It is an antineoplastic agent, which acts as a specific inhibitor of DNA topoisomerase I. It is metabolised by carboxylesterase in most tissues to SN-38, which was found to be more active than irinotecan in purified topoisomerase I and more cytotoxic than irinotecan against several murine and human tumour cell lines. The inhibition of DNA topoisomerase I by irinotecan or SN-38 induces single-strand DNA lesions which blocks the DNA replication fork and are responsible for the cytotoxicity. This cytotoxic activity was found to be time-dependent and was specific to the S phase.

Injection (per 2ml) 40mg

• Accord-Irinotecan (Accord)
• Campto (Pfizer) originator
• Cipla-Irinotecan (Cipla Medpro)
• Irinotas (Eurolab)
• Irinotecan Safeline (Safeline Pharma)
• Mylan-Irinotecan (Xixia)
• Sandoz Irinotecan (Sandoz)

Injection (per 5ml) 100mg

• Accord-Irinotecan (Accord)
• Campto (Pfizer) originator
• Cipla-Irinotecan (Cipla Medpro)
• Irinotas (Eurolab))
• Irinotecan Safeline (Safeline Pharma)
• Mylan-Irinotecan (Xixia)
• Sandoz Irinotecan (Sandoz)