Campto

Leaflet attached to the packaging: patient information

CAMPTO, 20 mg/ml, concentrate for solution for infusion

Irinotecan hydrochloride

Read the leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this leaflet, you may need to read it again.
• In case of any doubts, consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is CAMPTO and what is it used for
• 2. Important information before using CAMPTO
• 3. How to use CAMPTO
• 4. Possible side effects
• 5. How to store CAMPTO
• 6. Package contents and other information

1. What is CAMPTO and what is it used for

The active substance of CAMPTO is irinotecan. Irinotecan is a semi-synthetic derivative of camptothecin. It belongs to the group of cytostatic (anticancer) drugs. CAMPTO inhibits the replication of DNA in dividing cells, thereby acting cytotoxically on cancer cells, leading to their destruction.
CAMPTO is used to treat patients with advanced colorectal cancer (colon and rectal cancer):

• in combination with 5-fluorouracil and folinic acid in patients who have not previously received chemotherapy for advanced cancer;
• as monotherapy in patients who have failed 5-fluorouracil treatment.

CAMPTO in combination with cetuximab is indicated for the treatment of patients with metastatic colorectal cancer, whose cells express epidermal growth factor receptor (EGFR), with wild-type KRAS gene, who have not been previously treated for metastatic colorectal cancer or have failed cytotoxic chemotherapy with CAMPTO.
CAMPTO in combination with 5-fluorouracil, folinic acid, and bevacizumab is indicated as a first-line treatment for patients with metastatic colorectal cancer (colon or rectal cancer).
CAMPTO in combination with capecitabine and bevacizumab or without bevacizumab is indicated as first-line treatment for patients with metastatic colorectal cancer (colon and rectal cancer).
The doctor will decide on the appropriate dosing schedule for CAMPTO, depending on the stage of the disease, the patient's condition, and response to treatment.

2. Important information before using CAMPTO

When not to use CAMPTO

• if the patient is allergic to the active substance or any of the other ingredients of this medicine (listed in section 6);
• in patients with chronic inflammatory bowel diseases and/or bowel obstruction;
• in breastfeeding women;
• in patients with serum bilirubin levels more than 3 times higher than the upper limit of normal (values considered normal);
• in patients with severe bone marrow disorders;
• in patients whose performance status according to the WHO classification is > 2 (patients with limited ability to perform personal activities, spending more than half or all day in bed, and patients requiring care from another person);
• if the patient is taking or has recently taken preparations containing St. John's wort;
• if the patient is to receive or has recently received live attenuated vaccines. These vaccines should not be administered during treatment with CAMPTO and for 6 months after the end of chemotherapy.

Additional contraindications for cetuximab or bevacizumab are listed in the patient information leaflets for these medicines. Patients taking cetuximab or bevacizumab with CAMPTO should read the information leaflets for these medicines.
Patient taking capecitabine with CAMPTO should read the information leaflet for capecitabine.

Warnings and precautions

Before starting treatment with CAMPTO, the doctor should discuss the use of the medicine in:

• patients with a risk of complications, especially those whose performance status according to the WHO classification is 2 (patients able to perform personal activities, but unable to work, spending about half of the day in bed);
• patients who will not be able to follow the recommendations for managing side effects (e.g. late diarrhea);
• patients with severe bone marrow failure;
• patients with initial serum bilirubin levels of at least 1.0 mg/dl, who have a significantly higher risk of developing grade 3 or 4 neutropenia during the first cycle of treatment. The doctor should recommend weekly blood morphology tests with a smear and inform the patient about the risks associated with neutropenia and related fever;
• patients with Gilbert's syndrome, a hereditary disease that can increase bilirubin levels and cause jaundice (yellowing of the skin and eyes);
• patients after previous pelvic or abdominal radiotherapy, or large body surface areas, who may require dose reduction due to increased risk of myelosuppression;
• patients with liver function disorders. The doctor should recommend liver function tests before and after each chemotherapy cycle;
• patients who have previously experienced acute cholinergic syndrome (early diarrhea, sweating, abdominal cramps, tearing, miosis, and salivation);
• patients with asthma;
• patients with tumor involvement of the lungs or with pre-existing lung disease, and those taking drugs toxic to the lungs, or undergoing radiotherapy;
• elderly patients;
• patients with bowel obstruction, who should not receive CAMPTO until the obstruction has resolved;
• patients with a history of heart disease, risk factors for heart disease, or taking cytotoxic chemotherapy.

It is recommended to administer prophylactic antiemetics before each administration of CAMPTO.
Caution should be exercised when administering CAMPTO, and extravasation of the medicine should be avoided. In case of extravasation, the area should be flushed and ice applied.
Caution should be exercised, as severe anaphylactic and pseudoanaphylactic reactions have been reported after administration of CAMPTO.
In dehydrated patients, dizziness has been observed, which may be a symptom of orthostatic hypotension (a sudden drop in blood pressure in people with normal or even high blood pressure, occurring as a result of quickly changing from a lying to a standing position or standing for a long time).
Acute renal failure has been observed, attributed to complications of infections or dehydration related to nausea, vomiting, and diarrhea. Renal impairment has also been reported, caused by tumor lysis syndrome.
Administration of live or live attenuated vaccines (e.g. yellow fever vaccine) to patients with impaired immunity due to the use of chemotherapeutic agents, including CAMPTO, may lead to serious infections and generalized allergic reactions, which can be fatal. Concomitant use of these vaccines is contraindicated during treatment with CAMPTO and for 6 months after the end of chemotherapy.
Inactivated or killed vaccines may be administered, but the response to such vaccines may be weakened.
Patient taking CAMPTO should use effective contraception during and at least 3 months after the end of treatment.
In patients with additional risk factors for cancer, CAMPTO has rarely caused thromboembolic events (pulmonary embolism, venous and arterial thrombosis).
Like other anticancer drugs, CAMPTO may have side effects, some of which are severe. In case of their occurrence, appropriate measures should be taken to reduce the risk of complications. Doctors prescribing CAMPTO have experience in using this type of medicine and alleviating side effects that may occur during treatment, but it is recommended that the patient read the section "Procedure in case of diarrhea" and follow the instructions contained therein.

Procedure in case of diarrhea

CAMPTO may cause diarrhea. Depending on when it occurs, two types of diarrhea are distinguished:

• early diarrhea (occurring within the first 24 hours after administration), which may be accompanied by the following symptoms:
• sweating;
• abdominal pain;
• tearing;
• visual disturbances;
• dizziness;
• blood pressure drop;
• malaise;
• excessive salivation. In case of early diarrhea, the patient should immediately inform their doctor, who will prescribe appropriate treatment.

The patient should not take any anti-diarrheal medications prescribed by the doctor to treat late diarrhea without consulting their doctor.

The patient should immediately inform their doctor if they experience:

• diarrhea accompanied by nausea and vomiting;
• diarrhea accompanied by fever;
• diarrhea that does not resolve despite 48 hours of treatment.

The patient should not use any other methods to treat diarrhea other than taking the anti-diarrheal medications prescribed by their doctor and drinking the aforementioned fluids.

CAMPTO and other medicines

The patient should tell their doctor about all medicines they are currently taking or have recently taken, as well as any medicines they plan to take.
CAMPTO may interact with many medicines and dietary supplements, which may increase or decrease the levels of this medicine in the blood. The patient should tell their doctor or pharmacist if they are taking any of the following medicines:

• preparations containing St. John's wort (Hypericum perforatum), which should not be taken with CAMPTO,
• ketokonazole (an antifungal medicine),
• rifampicin (an antibiotic),
• carbamazepine, phenobarbital, or phenytoin (medicines used to treat epilepsy and other neurological conditions),
• regorafenib, crizotinib, idelalisib, and apalutamide (medicines used to treat cancer),
• atazanavir (a medicine used to treat HIV infection),
• dexamethasone (an anti-inflammatory medicine, also used to prevent vomiting),
• diuretics,
• laxatives.

Before administering CAMPTO, the patient should tell their doctor, pharmacist, or nurse if they are currently or have recently undergone chemotherapy (and radiotherapy).
Anesthesia before surgery
If the patient is going to the hospital for surgery, they should tell the anesthesiologist about taking CAMPTO. CAMPTO interacts with anesthetics and muscle relaxants used for anesthesia.
The patient should contact their doctor if they experience severe diarrhea, leukopenia, or neutropenia while taking bevacizumab with CAMPTO.
When taking CAMPTO with other anticancer medicines, such as cetuximab, capecitabine, or bevacizumab, the patient should read the patient information leaflets for these medicines.

Pregnancy and breastfeeding

Women of childbearing age should use effective contraception during treatment with CAMPTO and for 6 months after the end of treatment.
Men with female partners of childbearing age should use effective contraception during treatment with CAMPTO and for 3 months after the end of treatment.
Pregnancy
If the patient is pregnant or breastfeeding, thinks they may be pregnant, or plans to have a child, they should consult their doctor before using this medicine.
CAMPTO should not be used in pregnant women. Women of childbearing age should not start treatment with CAMPTO until pregnancy has been ruled out.
If the patient becomes pregnant, they should immediately inform their doctor.
Breastfeeding
CAMPTO should not be used during breastfeeding.

Driving and using machines

The effect of CAMPTO on the ability to drive and use machines has not been studied. However, during treatment with CAMPTO, dizziness and visual disturbances may occur. If these side effects occur, the patient should not drive or operate machines.

CAMPTO contains sorbitol (E 420)

Sorbitol is a source of fructose. If the patient has been diagnosed with hereditary fructose intolerance, a rare genetic disease, they should not take this medicine. In patients with hereditary fructose intolerance, the body does not break down the fructose contained in this medicine, which can cause severe side effects.
The patient should inform their doctor before taking this medicine if they have hereditary fructose intolerance.
This medicine contains 45 mg of sorbitol in 1 ml of concentrate for solution for infusion, which corresponds to 90 mg/2 ml, 225 mg/5 ml, 675 mg/15 ml.

CAMPTO contains sodium

The medicine contains less than 1 mmol (23 mg) of sodium per dose, which means the medicine is considered "sodium-free".
The medicine can be diluted in 0.9% sodium chloride solution. The sodium content from the diluent should be taken into account when calculating the total sodium content in the prepared dilution of the medicine. To obtain accurate information about the sodium content in the solution used to dilute the medicine, the patient should read the patient information leaflet for the diluent used.

3. How to use CAMPTO

CAMPTO will be administered under the supervision of a doctor qualified to use anticancer treatment, in a hospital department specialized in the administration of cytostatics.
This medicine should always be used according to the doctor's instructions. In case of doubts, the patient should consult their doctor.
Detailed information on dosing and administration intended for healthcare professionals is provided at the end of the leaflet.
The solution for infusion of CAMPTO is administered into a peripheral or central vein. The medicine is only used in adults.
Recommended dosing
The doctor will prescribe the appropriate dosing schedule for CAMPTO, used alone (monotherapy) or in combination with other medicines (combination therapy).
Dose modifications
The doctor will prescribe the appropriate dose adjustment of CAMPTO, depending on the severity of side effects that occurred after administration of the medicine (e.g. diarrhea) or during the previous treatment cycle, as well as in case of concomitant use of other medicines.
Special patient groups
Patient with liver function disorders
In monotherapy: the doctor will prescribe the appropriate dose adjustment of CAMPTO and perform complete blood counts.
Combination therapy: there are no data on patients with liver function disorders treated with CAMPTO in combination chemotherapy.
Patient with kidney function disorders
CAMPTO should not be used in patients with kidney function disorders, as clinical trials have not been conducted in this patient group.
Patient over 65 years of age
Due to the more frequent occurrence of organ disorders in this patient group, the doctor will exercise particular caution when selecting the dose and will recommend close monitoring of the patient.

Use of a higher than recommended dose of CAMPTO

Since the medicine will be administered under medical supervision, the use of a higher than recommended dose is unlikely. In case of doubts about the use of the medicine, the patient should consult their doctor or nurse.

Missing a dose of CAMPTO

Since the medicine will be administered under medical supervision, missing a dose is unlikely.

Stopping treatment with CAMPTO

The doctor will decide on stopping treatment with CAMPTO.
In case of doubts about the use of this medicine, the patient should consult their doctor.

4. Possible side effects

Like all medicines, CAMPTO can cause side effects, although not everybody gets them.
The doctor should inform the patient about possible side effects. In case of some side effects, it is very important to take immediate action. The following side effects are described in clinical trials and reported after the medicine was placed on the market as part of pharmacovigilance.
The following side effects have been ranked according to their frequency of occurrence as:

• Very common(may occur in more than 1 in 10 people):
• neutropenia (reduced number of neutrophils)
• anemia
• decreased appetite
• cholinergic syndrome (symptoms: rhinitis, increased salivation, miosis, lacrimation, sweating, flushing, bradycardia, dizziness, conjunctivitis, visual disturbances)
• diarrhea
• vomiting
• nausea
• abdominal pain
• alopecia (reversible)
• mucositis
• fever
• asthenia (weakness)

Common(may occur in up to 1 in 10 people):

• infection
• thrombocytopenia
• febrile neutropenia
• constipation
• increased creatinine levels in the blood
• increased aminotransferase activity (ALT and AST)
• increased bilirubin levels
• increased alkaline phosphatase activity

Frequency not known(cannot be estimated from the available data):

• pseudomembranous colitis
• sepsis
• fungal infections
• viral infections
• peripheral thrombocytopenia with platelet antibodies
• dehydration (due to diarrhea and vomiting)
• hypovolemia
• hypersensitivity reactions
• anaphylactic reactions
• transient speech disorders
• paresthesia
• hypertension
• cardiac collapse
• interstitial lung disease
• dyspnea
• hiccups
• intestinal obstruction
• megacolon
• gastrointestinal bleeding
• colitis; in some cases complicated by ulceration, bleeding, obstruction, or infection
• proctitis
• ischemic colitis
• ulcerative colitis
• gastrointestinal bleeding
• increased activity of pancreatic enzymes with or without symptoms
• intestinal perforation
• fatty liver disease
• skin reactions
• infusion site reactions
• increased amylase activity in the blood
• increased lipase activity
• hypokalemia
• hyponatremia (decreased sodium levels in the blood) mostly in the course of diarrhea and vomiting
• increased aminotransferase activity in serum (i.e. AST and ALT), in the absence of progressive liver metastases, very rarely reported
• muscle spasms
• renal disorders and acute renal failure in patients with infections and/or dehydration caused by toxins in the gastrointestinal tract
• renal failure
• hypertension

When using CAMPTO with cetuximab, additional side effects may occur, related to the use of both medicines (e.g. acne-like rash). It is recommended to read the patient information leaflet for cetuximab.
When using CAMPTO with bevacizumab, additional side effects may occur, related to the use of both medicines. It is recommended to read the patient information leaflet for bevacizumab.
When using CAMPTO with capecitabine, additional side effects may occur, related to the combined use of both medicines. Such side effects include very common: thrombosis; common: allergic reactions, myocardial infarction, and fever in patients with decreased white blood cell count. It is recommended to read the patient information leaflet for capecitabine.
When using CAMPTO with capecitabine and bevacizumab, additional side effects may occur, related to the combined use of these medicines. Such side effects include decreased white blood cell count, thrombosis, high blood pressure, and myocardial infarction. Therefore, it is recommended to read the patient information leaflet for capecitabine or bevacizumab.

Reporting side effects

If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor. Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder or its representative.
Reporting side effects will help to gather more information on the safety of the medicine.

5. How to store CAMPTO

The medicine should be stored out of sight and reach of children.
Store in a temperature below 25°C, protected from light.
The diluted solution should be used immediately after preparation.
If the solution is prepared under aseptic conditions (laminar flow cabinet), the solution should be administered to the patient (completed intravenous infusion) within 12 hours at room temperature or within 24 hours (including infusion time) if the solution has been stored from preparation in a refrigerator at a temperature between 2°C and 8°C.
Do not use this medicine after the expiry date stated on the label and carton after: EXP.
The expiry date refers to the last day of the month stated.
Medicines should not be disposed of via wastewater or household waste. All materials and equipment used to prepare and administer the medicine should be disposed of in accordance with standard procedures for the disposal of cytotoxic waste. This will help protect the environment.

6. Package contents and other information

What CAMPTO contains

• The active substance of CAMPTO is irinotecan hydrochloride trihydrate.
• The other ingredients of the medicine are: D-sorbitol (E 420), lactic acid, sodium hydroxide, water for injections. One ml of concentrate for solution for infusion contains 20 mg of irinotecan hydrochloride trihydrate, which corresponds to 17.33 mg of irinotecan. Each 2 ml vial contains 40 mg of irinotecan hydrochloride trihydrate, which corresponds to 34.66 mg of irinotecan. Each 5 ml vial contains 100 mg of irinotecan hydrochloride trihydrate, which corresponds to 86.65 mg of irinotecan. Each 15 ml vial contains 300 mg of irinotecan hydrochloride trihydrate, which corresponds to 259.95 mg of irinotecan.

What CAMPTO looks like and contents of the pack

CAMPTO is a clear, slightly yellow liquid.
Pack contents:
1 vial of 2 ml (40 mg/2 ml) made of brown polypropylene in a cardboard box;
or
1 or 5 vials of 5 ml (100 mg/5 ml) made of brown polypropylene in a cardboard box;
or
1 vial of 15 ml (300 mg/15 ml) made of brown polypropylene in a cardboard box.

Marketing authorization holder:

Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Brussels
Belgium

Manufacturer:

Pfizer Service Company BV
Hoge Wei 10
1930 Zaventem
Belgium
To obtain more detailed information on this medicine, the patient should contact the representative of the marketing authorization holder:
Pfizer Polska Sp. z o.o.
phone: 22 335 61 00
Date of last revision of the leaflet:08/2022

Information intended for healthcare professionals only:

Recommended dosing

Monotherapy (in patients previously treated)
The recommended dose of CAMPTO is 350 mg/m² administered once every 3 weeks, as an intravenous infusion lasting from 30 to 90 minutes.
Combination therapy (in patients not previously treated)
The safety and efficacy of CAMPTO in combination with 5-fluorouracil (5-FU) and folinic acid (FA) have been established in the following dosing schedule:
CAMPTO with 5-FU/FA in a 2-week schedule
The recommended dose of CAMPTO is 180 mg/m² administered once every 2 weeks as an intravenous infusion lasting from 30 to 90 minutes, followed by an intravenous infusion of folinic acid and 5-fluorouracil.
CAMPTO in combination with 5-fluorouracil (5-FU) and leucovorin in a 2-week schedule
It is recommended to use irinotecan in combination with 5-FU and leucovorin in the treatment of patients with metastatic colorectal cancer. In all schedules, leucovorin should be administered immediately after irinotecan, and 5-FU immediately after leucovorin.
Data on dosing and administration of CAMPTO with cetuximab can be found in the Summary of Product Characteristics for cetuximab.
Data on dosing and administration of bevacizumab can be found in the Summary of Product Characteristics for bevacizumab.
Data on dosing and administration of CAMPTO with capecitabine can be found in the relevant sections of the Summary of Product Characteristics for capecitabine.

Dose modifications

CAMPTO can be administered after the severity of side effects has decreased to grade 0 or 1 according to the NCI-CTC (National Cancer Institute Common Toxicity Criteria) and after complete resolution of diarrhea related to the administration of the medicine.
The dose of CAMPTO and 5-FU can be reduced in the next chemotherapy cycle, depending on the severity of side effects during the previous cycle of treatment.
Treatment can be delayed by 1 to 2 weeks to allow side effects related to the administration of the medicine to resolve.
The dose of CAMPTO and/or 5-FU should be reduced by 15-20% in case of the following side effects:

• hematologic toxicity - grade 4 neutropenia, neutropenia with fever (grade 3-4 neutropenia and grade 2-4 fever), thrombocytopenia, and grade 4 leukopenia;
• non-hematologic toxicity (grade 3-4).

In case of concomitant use of cetuximab with irinotecan, the recommendations for dose modification of cetuximab should be followed, as stated in the Summary of Product Characteristics for cetuximab.
In case of concomitant use of bevacizumab with CAMPTO in combination with 5-fluorouracil and folinic acid (CAMPTO/5-FU/FA), the recommendations for dose modification should be followed, as stated in the Summary of Product Characteristics for bevacizumab.
In case of concomitant use of capecitabine with CAMPTO, in patients over 65 years of age, the initial dose of capecitabine should be reduced to 800 mg/m² twice daily, as stated in the Summary of Product Characteristics for capecitabine. The recommendations for dose modification should also be followed, as stated in the Summary of Product Characteristics for capecitabine.

Duration of treatment

Treatment with CAMPTO should be continued until disease progression or significant increase in side effects.

Incompatibilities

None are known. The medicinal product should not be mixed with other medicinal products.

Preparation and administration of the solution for infusion

As with other anticancer medicines, the solution for infusion of CAMPTO should be prepared and stored with special precautions. Protective glasses, masks, and gloves are required.
If the concentrate of CAMPTO or the diluted solution comes into contact with the skin, it should be immediately and thoroughly washed with soap and water. If it comes into contact with the mucous membranes, they should be immediately rinsed with water.
Like other intravenous medicines, the solution for infusion of CAMPTO must be prepared under aseptic conditions.
Aseptically, the required amount of CAMPTO should be drawn from the vial into a calibrated syringe and added to 250 ml of infusion fluid in a bottle or container containing 0.9% sodium chloride solution or 5% glucose solution. The resulting solution should be thoroughly mixed and administered into a peripheral or central vein. The medicine should not be administered by intravenous injection, or by infusion lasting less than 30 minutes or more than 90 minutes.
If a precipitate forms in the vial or in the prepared infusion solution, the medicine should not be administered to patients and should be disposed of in accordance with standard procedures for the disposal of cytotoxic waste.

Disposal of leftover medicine and packaging

All materials and equipment used to prepare and administer the medicine should be disposed of in accordance with standard procedures for the disposal of cytotoxic waste.