Campto

/ Pfizer

For adults only. Irinotecan solution for infusion should be infused into a peripheral or central vein.
Recommended dosage: In monotherapy (for previously treated patient): The recommended dosage of CAMPTO® is 350 mg/m² administered as an intravenous infusion over a 30- to 90- minute period every three weeks.
In combination therapy (for previously untreated patient): Safety and efficacy of CAMPTO® in combination with 5-fluorouracil (5FU) and folinic acid (FA)-See prescribing information for full details.
– CAMPTO® plus 5FU/FA in every 2 weeks schedule: The recommended dose of CAMPTO® is 180 mg/m² administered once every 2 weeks as an
intravenous infusion over a 30- to 90-minute period, followed by infusion with folinic acid and 5- fluorouracil.
Dosage adjustments: Irinotecan should be administered after appropriate recovery of all adverse events to Grade 0 or 1 NCI-CTC grading (National Cancer Institute Common Toxicity Criteria) and when treatment-related diarrhoea is fully resolved. At the start of a subsequent infusion of therapy, the dose of Irinotecan, and 5FU when applicable, should be decreased according to the worst Grade of adverse events observed in the prior infusion. Treatment should be delayed by 1 to 2 weeks to allow recovery from treatment-related adverse events. With the following adverse events a dose reduction of 15 to 20% should be applied for Irinotecan and/or 5FU when applicable: Hematological toxicity (neutropenia Grade 4, febrile neutropenia (neutropenia Grade 3-4 and fever Grade 2-4), thrombocytopenia and leukopenia (Grade 4), Non -haematological toxicity (Grade 3-4).
Treatment duration: Treatment should be continued until there is an objective progression of the disease or an unacceptable toxicity.
Patients with impaired hepatic function: In monotherapy: Blood bilirubin levels (up to 3 times the upper limit of the normal range (ULN)) in patients with performance status  2, should determine the starting dose of Irinotecan. In these patients with hyperbilirubinemia and prothrombin time greater than 50%, the clearance of irinotecan is decreased and therefore the risk of hepatotoxicity is increased. Thus, weekly monitoring of complete blood counts should be conducted in this patient population. In patients with bilirubin up to 1.5 times the upper limit of the normal range (ULN), the recommended dosage of Irinotecan is 350 mg/m², In patients with bilirubin ranging from 1.5 to 3 times the ULN, the recommended dosage of Irinotecan is 200 mg/m², Patients with bilirubin beyond to 3 times the ULN should not be treated with Irinotecan No data are available in patients with hepatic impairment treated by Irinotecan in combination.
Patients with impaired renal function: Irinotecan is not recommended for use in patients with impaired renal function, as studies in this population have not been conducted.
Elderly: No specific pharmacokinetic studies have been performed in elderly. However, the dose should be chosen carefully in this population due to their greater frequency of decreased biological functions. This population should require more intense surveillance.

Irinotecan  is indicated for the treatment of patients with metastatic colorectal cancer: In combination with 5-fluorouracil and folinic acid in patients without prior chemotherapy for metastatic disease. As a single agent in patients who have failed an established 5-fluorouracil containing treatment regimen. For the treatment of patients with small cell lung cancer. For the treatment of patients with gastric cancer. Irinotecan in combination with leucovorin, oxaliplatin and 5-fluorouracil for the first-line treatment of patients with metastatic pancreatic adenocarcinoma.

Chronic inflammatory bowel disease and/or bowel obstruction. Hypersensitivity to the active substance(s) or to any of the excipients. Lactation. Bilirubin > 3 times the upper limit of the normal range. Severe bone marrow failure. WHO performance status > 2. Concomitant use with St John’s Wort. Live attenuated vaccines.

Given the nature and incidence of adverse events, Irinotecan will only be prescribed in the following cases after the expected benefits have been weighted against the possible therapeutic risks: In patients presenting a risk factor, particularly those with a WHO performance status = 2. In the few rare instances where patients are deemed unlikely to observe recommendations regarding management of adverse events (need for immediate and prolonged antidiarrhoeal treatment combined with high fluid intake at onset of delayed diarrhoea). Strict hospital supervision is recommended for such patients. When Irinotecan is used in monotherapy, it is usually prescribed with the every-3-weekdosage schedule. However, the weekly-dosage schedule  may be considered in patients who may need a closer follow-up or who are at particular risk of severe neutropenia.
Delayed diarrhoea
Patients should be made aware of the risk of delayed diarrhoea occurring more than 24 hours after the administration and at any time before the next cycle. In monotherapy, the median time of onset of the first liquid stool was on day 5 after the infusion of the drug. Patients should quickly inform their physician of its occurrence and start appropriate therapy immediately.
Patients with an increased risk of diarrhoea are those who had a previous abdominal/pelvic radiotherapy, those with baseline hyperleucocytosis, those with performance status ≥ 2 and women. If not properly treated, diarrhoea can be life-threatening, especially if the patient is concomitantly neutropenic.
Haematology
In clinical studies, the frequency of NCI CTC Grade 3 and 4 neutropenia has been significantly higher in patients who received previous pelvic/abdominal irradiation than in those who had not received such irradiation. Patients with baseline serum total bilirubin levels of 1.0 mg/dL or more have also had a significantly greater likelihood of experiencing first-cycle Grade 3 or 4 neutropenia than those with bilirubin levels that were less than 1.0 mg/dL.
Weekly monitoring of complete blood cell counts is recommended during  treatment. Patients should be aware of the risk of neutropenia and the significance of fever. Febrile neutropenia (temperature > 38°C and neutrophil count ≤ 1,000 cells/mm³) should be urgently treated in the hospital with broad-spectrum intravenous antibiotics.
Patients with reduced UGT1A1 activity
Patients that are UGT1A1 poor metabolisers, such as patients with Gilbert’s syndrome (e.g. homozygous for UGT1A1*28 or *6 variants) are at increased risk for severe neutropenia and diarrhoea following irinotecan treatment. This risk increases with the irinotecan dose level.
Although a precise dose reduction in starting dose has not been established, a reduced irinotecan starting dose should be considered for patients that are UGT1A1 poor metabolisers, especially patients who are administered doses > 180 mg/m2 or frail patients. Consideration should be given to applicable clinical guidelines for dose recommendations in this patient population. Subsequent doses may be increased based on individual patient tolerance to treatment.
UGT1A1 genotyping can be used to identify patients at increased risk of severe neutropenia and diarrhoea, however the clinical utility of pre-treatment genotyping is uncertain, since UGT1A1 polymorphism does not account for all the toxicity seen from irinotecan therapy.
Liver impairment
Liver function tests should be performed at baseline and before each cycle.
Weekly monitoring of complete blood counts should be conducted in patients with bilirubin ranging from 1.5 to 3 times the ULN, due to decrease of the clearance of irinotecan and thus increasing the risk of hematotoxicity in this population. For patients with a bilirubin > 3 times the ULN.
Nausea and vomiting
A prophylactic treatment with antiemetics is recommended before each treatment with CAMPTO®. Nausea and vomiting have been frequently reported. Patients with vomiting associated with delayed diarrhoea should be hospitalised as soon as possible for treatment.
Acute cholinergic syndrome
If acute cholinergic syndrome appears (defined as early diarrhoea and various other signs and symptoms such as sweating, abdominal cramping, myosis and salivation), atropine sulphate (0.25 mg subcutaneously) should be administered unless clinically contraindicatedץ
Respiratory disorders
Interstitial lung disease presenting as lung infiltration is uncommon during irinotecan therapy. Interstitial lung disease can be fatal. Risk factors possibly associated with the development of interstitial lung disease include the use of pneumotoxic medicinal products, radiation therapy and colony stimulating factors. Patients with risk factors should be closely monitored for respiratory symptoms before and during irinotecan therapy.
Extravasation
While irinotecan is not a known vesicant, care should be taken to avoid extravasation and the infusion site should be monitored for signs of inflammation. Should extravasation occur, flushing the site and application of ice is recommended.
Elderly
Due to the greater frequency of decreased biological functions, in particular hepatic function, in elderly patients, dose selection with CAMPTO® should be cautious in this population.
Chronic inflammatory bowel disease and/or bowel obstruction
Patients must not be treated until resolution of the bowel obstruction.
Renal function
Increases in serum creatinine or blood urea nitrogen have been observed. There have been cases of acute renal failure. These events have generally been attributed to complications of infection or to dehydration related to nausea, vomiting, or diarrhoea. Rare instances of renal dysfunction due to tumour lysis syndrome have also been reported.
Irradiation therapy
Patients who have previously received pelvic/abdominal irradiation are at increased risk of myelosuppression following the administration of irinotecan. Physicians should use caution in treating patients with extensive prior irradiation (e.g.,>25% of bone marrow irradiated and within 6 weeks prior to start of treatment with irinotecan). Dosing adjustment may apply to this population.
Cardiac disorders
Myocardial ischaemic events have been observed following irinotecan therapy predominately in patients with underlying cardiac disease, other known risk factors for cardiac disease, or previous cytotoxic chemotherapy.
Consequently, patients with known risk factors should be closely monitored, and action should be taken to try to minimize all modifiable risk factors (e.g., smoking, hypertension, and hyperlipidaemia).
Vascular disorders
Irinotecan has been rarely associated with thromboembolic events (pulmonary embolism, venous thrombosis, and arterial thromboembolism) in patients presenting with multiple risk factors in addition to the underlying neoplasm.
Others
Concomitant administration of irinotecan with a strong inhibitor (e.g. ketoconazole) or inducer (e.g. rifampicin, carbamazepine, phenobarbital, phenytoin, apalutamide) of CYP3A4 may alter the metabolism of irinotecan and should be avoided.
Infrequent cases of renal insufficiency, hypotension or circulatory failure have been observed in patients who experienced episodes of dehydration associated with diarrhoea and/or vomiting, or sepsis.
Contraception in women of childbearing potential/  men
Due to the potential for genotoxicity, advise female patients of reproductive potential to use highly effective contraception during treatment and for 6 months after the last dose of irinotecan.
Due to the potential for genotoxicity, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of irinotecan.
Breast-feeding
Due to the potential for adverse reactions in nursing infants, breast-feeding should be discontinued for the duration of therapy.
See prescribing information for full details.

Decreased appetite, alopecia, vomiting, nausea, diarrhea, constipation, abdominal pain, pyrexia.
See prescribing information for full details.

Yellow fever vaccine: Risk of fatal generalised reaction to vaccines
Saint John’s Wort: Decrease in the active metabolite of irinotecan, SN-38, plasma levels.
Live attenuated vaccines: Risk of generalised reaction to vaccines, possibly fatal. Concomitant use is contraindicated during treatment with irinotecan and for 6 months following discontinuation of chemotherapy. Killed or inactivated vaccines may be administered; however, the response to such vaccines may be diminished.
See prescribing information for full details. 

Pregnancy: There is no data from the use of irinotecan in pregnant women. Irinotecan has been shown to be embryotoxic and teratogenic in animals.
Lactation: 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, breast-feeding should be discontinued for the duration of therapy.
See prescribing information for full details.

Symptoms: There have been reports of overdosage at doses up to approximately twice the recommended therapeutic dose, which may be fatal. The most significant adverse reactions reported were severe neutropenia and severe diarrhoea.
Management: There is no known antidote for CAMPTO®. Maximum supportive care should be instituted to prevent dehydration due to diarrhoea and to treat any infectious complications.

Storage: Store below 30°C. Store in the original package in order to protect from light.
Compatibility: None known. In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Excipients:
This medicine contains sorbitol. Sorbitol is a source of fructose. Patients with hereditary fructose intolerance (HFI) must not be given unless strictly necessary.
Babies and young children (below 2 years of age) may not yet be diagnosed with HFI. Medicines (containing fructose) given intravenously may have life-threatening effects in individuals with HFI and should not be administered in this population unless there is an overwhelming clinical need and no alternatives are available.
A detailed history with regard to HFI symptoms has to be taken of each patient prior to being given this medicinal product.
This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.