Camptosar

Serious side effects have occurred with use of Camptosar.

• You may experience the following symptoms while you are receiving a dose of Camptosar or for up to 24 hours afterward: runny nose, increased saliva, shrinking pupils (black circles in the middle of the eyes), watery eyes, sweating, flushing, diarrhea (sometimes called 'early diarrhea'), and stomach cramps. Tell your doctor if you experience any of these symptoms. Your doctor can give you medication to prevent or treat these symptoms.
• You may also experience severe diarrhea (sometimes called ''late diarrhea'') more than 24 hours after you receive Camptosar. This type of diarrhea can be life threatening since it can last a long time and lead to dehydration, infection, kidney failure, and other problems. Tell your doctor if you have or have ever had a bowel obstruction (blockage in your intestine). Tell your doctor and pharmacist if you are taking any of the following medications: other chemotherapy medications for cancer; diuretics ('water pills'); or laxatives such as bisacodyl (Dulcolax) or senna (in Correctol, Ex-Lax, Peri-Colace, Senokot).
• Before you begin your treatment with Camptosar, talk to your doctor about what to do if you have late diarrhea. Your doctor will probably tell you to keep loperamide (Imodium AD) on hand so that you can begin to take it right away if you develop late diarrhea. Your doctor will probably tell you to take loperamide at regular intervals throughout the day and night. Be sure to follow your doctor's directions for taking loperamide; these will be different than the directions printed on the package label of loperamide. Your doctor will also tell you which foods you should eat and which foods you should avoid to control diarrhea during your treatment. Drink plenty of fluids and follow this diet carefully.
• Call your doctor right away the first time you have diarrhea during your treatment. Also call your doctor immediately if you experience any of the following symptoms: fever (temperature higher than 100.4°F); shaking chills; black or bloody stools; diarrhea that does not stop within 24 hours; lightheadedness, dizziness, or fainting; or severe nausea and vomiting that stops you from drinking anything. Your doctor will watch you carefully and may treat you with fluids or antibiotics if needed.
• Camptosar may cause a decrease in the number of blood cells made by your bone marrow. Tell your doctor if you have or have ever had a blood disease or Gilbert's syndrome (decreased ability to break down bilirubin, a natural substance in the body) and if you are being treated with radiation to your stomach or pelvis (area between the hip bones) or if you have ever been treated with this type of radiation. If you experience any of the following symptoms, call your doctor immediately: fever, chills, cough, or other signs of infection; shortness of breath; fast heartbeat; headache; dizziness;pale skin; confusion; extreme tiredness, or unusual bleeding or bruising.

Do not take Camptosar if you are allergic to it or to any of the inactive ingredients.

Before receiving Camptosar,

• tell your doctor and pharmacist if you are allergic to Camptosar, sorbitol, or any other medications.
• tell your doctor if you are taking ketoconazole (Nizoral). Your doctor will probably tell you not to take ketoconazole for one week before you begin your treatment with Camptosar or during your treatment.
• tell your doctor if you are taking St. John's wort. You should not take St. John's wort for 2 weeks before you begin your treatment with Camptosar or during your treatment.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements and herbal products you are taking or plan to take.
• tell your doctor if you have or have ever had diabetes; fructose intolerance (inability to digest the natural sugar found in fruit); or liver, lung, or kidney disease.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. You should not become pregnant while you are receiving Camptosar. Talk to your doctor about birth control methods that will work for you. If you become pregnant while receiving Camptosar, call your doctor. Camptosar may harm the fetus (unborn baby).
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are receiving Camptosar.
• you should know that Camptosar may make you dizzy or affect your vision, especially during the first 24 hours after you receive a dose. Do not drive a car or operate machinery until you know how this medication affects you.
• talk to your doctor before you receive any vaccinations during your treatment with Camptosar.

Before you are treated with irinotecan, tell your doctor about all other cancer medicines you have recently used.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• nefazodone;

• St. John's wort;

• an antibiotic--clarithromycin, erythromycin, telithromycin;

• antifungal medicine--itraconazole, ketoconazole, voriconazole;

• seizure medicine--carbamazepine, fosphenytoin, oxcarbazepine, phenobarbital, phenytoin, primidone; or

• antiviral medicine to treat hepatitis or HIV/AIDS--atazanavir, boceprevir, cobicistat (Stribild, Tybost), delavirdine, efavirenz, fosamprenavir, indinavir, nelfinavir, nevirapine, ritonavir, saquinavir, telaprevir.

This list is not complete. Other drugs may interact with irinotecan, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Distribution

Extent

Irinotecan crosses the placenta and is distributed into milk in rats.1 65

Plasma Protein Binding

Conventional irinotecan: 30–68% (irinotecan) and 95% (SN-38), mainly to albumin.1

Liposomal irinotecan: <0.44% of total irinotecan; 95% of irinotecan remains encapsulated in liposomes.65

Elimination

Metabolism

Partially metabolized via CYP3A4 to oxidative metabolites.1 65 c d

Metabolized via carboxylesterases1 65 to the active metabolite SN-38 (7-ethyl-10-hydroxycamptothecin), which is 1000 times as potent as irinotecan in vitro as a topoisomerase I inhibitor.1 2 4 7 8 9 10 11 13 14 16 18 19 28 c d

SN-38 undergoes conjugation via UGT1A1 to form a glucuronide metabolite.1 65 c d

Elimination Route

Disposition not fully elucidated.1 65 Excreted in urine as irinotecan (11–20%), SN-38 (<1%), and SN-38 glucuronide (3%).1 65

Half-life

Conventional irinotecan: 6–12 hours (irinotecan) and 10–20 hours (SN-38).1

Liposomal irinotecan: 26 hours (irinotecan) and 68 hours (SN-38).65

Special Populations

Patients with hepatic impairment receiving conventional irinotecan: Decreased clearance of irinotecan and increased exposure to SN-38; magnitude of effect is proportional to elevation in bilirubin and aminotransferase concentrations.1

Patients with hepatic impairment receiving liposomal irinotecan: Average steady-state concentrations of SN-38 increased by 37% in patients with bilirubin concentrations of 1–2 mg/dL compared with those with bilirubin concentrations <1 mg/dL.65 Elevated ALT/AST concentrations did not substantially alter SN-38 concentrations.65

Patients with renal impairment: Conventional irinotecan not evaluated.1

Patients with renal impairment receiving liposomal irinotecan: Mild to moderate renal impairment (Clcr 30–89 mL/minute) did not substantially alter exposure to SN-38.65 Limited data in severe renal impairment (Clcr<30 mL/minute).65

Geriatric patients receiving conventional irinotecan (weekly dosage schedule): Age ≥65 years did not substantially alter exposure to irinotecan, SN-38, or SN-38 glucuronide.1

Geriatric patients receiving liposomal irinotecan: Age (range: 28–87 years) did not substantially affect exposure to irinotecan and SN-38.65

Pediatric patients receiving conventional irinotecan: Clearance of irinotecan and exposure to SN-38 similar to values in adults.1 Minimal accumulation of irinotecan and SN-38.1

Gender: No influence on pharmacokinetics.1 65

UGT1A1*28 genetic polymorphism: In individuals homozygous for UGT1A1*28 allele, reduced UGT1A1 activity results in increased exposure to SN-38.1 65

Storage

Parenteral

Conventional irinotecan: 15–30°C; protect from light.1 Store vial in carton until time of use.1 Following dilution, store at 15–30°C and use within 4 hours; if diluted under strict aseptic (e.g., laminar airflow) conditions, use within 12 hours.1 Alternatively, store at 2–8°C and use within 24 hours; protect refrigerated solutions from light.1 Do not refrigerate solutions prepared in 0.9% sodium chloride.1 Do not freeze.1

Liposomal irinotecan: 2–8°C.65 Following dilution, store at 15–30°C and use within 4 hours; alternatively, store at 2–8°C and use within 24 hours.65 Protect concentrate and diluted solutions from light; do not freeze.65

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Distribution of liposomal irinotecan is restricted.66 (See Restricted Distribution Program for Liposomal Irinotecan under Dosage and Administration.)

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

• Anxiety
• black, tarry stools
• blood in the urine or stools
• blurred vision
• changes in skin color
• chest pain or discomfort
• chest tightness or heaviness
• chills
• clay colored stools
• cold hands and feet
• confusion
• constricted pupils
• cough or hoarseness
• dark urine
• diarrhea with or without stomach cramps or sweating
• dizziness
• fainting
• fast, slow, or irregular heartbeat
• fever
• full or bloated feeling or pressure in the stomach
• headache
• increased production of saliva
• increased tear production
• itching
• lightheadedness when getting up suddenly from a lying or sitting position
• loss of appetite
• low blood pressure or pulse
• lower back or side pain
• nausea or vomiting
• numbness or tingling in the face, arms, or legs
• pain
• pain in the chest, groin, or legs, especially calves of the legs
• pain in the shoulders, arms, jaw, or neck
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• redness or swelling of the leg
• runny nose
• severe headache of sudden onset
• shortness of breath or troubled breathing
• skin rash
• slow breathing
• slurred speech
• sore throat
• stomach pain
• stopping of the heart
• sudden and severe weakness in the arm or leg on one side of the body
• sudden loss of coordination
• sudden vision changes
• sweating
• swelling
• swelling of the abdomen or stomach area
• temporary blindness
• tenderness, pain, or swelling of the arm, foot, or leg
• trouble with speaking or walking
• ulcers, sores, or white spots on the lips or in the mouth
• unconsciousness
• unpleasant breath odor
• unusual bleeding or bruising
• unusual tiredness or weakness
• vomiting of blood
• warm, red feeling over the body
• yellow eyes or skin

• Bleeding gums
• coughing up blood
• decreased urination
• difficulty with swallowing
• dryness of the mouth
• increased menstrual flow or vaginal bleeding
• increased thirst
• nosebleeds
• paralysis
• prolonged bleeding from cuts
• sneezing
• wheezing
• wrinkled skin

• Decreased amount of urine
• decreased frequency of urination
• fast, irregular, or troubled breathing
• hives
• increased blood pressure
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rapid weight gain

• Abdominal or stomach pain and tenderness
• agitation
• bloated or full feeling
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• coma
• constipation
• depression
• heartburn or indigestion
• hostility
• irritability
• lethargy
• muscle pain and cramps
• muscle twitching
• pain in the stomach, side, or abdomen, possibly radiating to the back
• pain or discomfort in the arms, jaw, back, or neck
• rectal bleeding
• severe abdominal or stomach cramping or burning
• severe and continuing nausea
• stupor
• swelling of the face, lower legs, ankles, fingers, or hands
• tightness in the chest
• unusual tiredness or weakness
• vomiting of material that looks like coffee grounds

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Acid or sour stomach
• belching
• blistering, peeling, redness, or swelling of the palms of hands or bottoms of the feet
• cracked lips
• excess air or gas in the stomach or intestines
• feeling of constant movement of self or surroundings
• numbness, pain, tingling, or unusual sensations in the palms of hands or bottoms of feet
• passing gas
• right upper abdominal or stomach pain and fullness
• sensation of spinning
• sleepiness or unusual drowsiness
• sleeplessness
• stomach discomfort, upset, or pain
• trouble sleeping
• unable to sleep
• weight loss

• Hiccups

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about this medicine, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take Camptosar or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to Camptosar. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Camptosar Injection is available in three single-dose sizes:

• 2 mL-fill vial containing 40 mg irinotecan hydrochloride
• 5 mL-fill vial containing 100 mg irinotecan hydrochloride
• 15 mL-fill vial containing 300 mg irinotecan hydrochloride

Camptosar Injection is available in single-dose brown glass vials in the following package sizes:

Camptosar Injection is available in single-dose amber colored polypropylene CYTOSAFE® vials in the following package sizes:

Store at controlled room temperature 15° to 30°C (59° to 86°F). Protect from light. Keep the vial in the carton until the time of use.

Inspect the vial for damage and visible signs of leaks before removing from the carton. If damaged, incinerate the unopened package.

You should not use Camptosar if you are allergic to irinotecan.

To make sure Camptosar is safe for you, tell your doctor if you have:

• liver or kidney disease;

• diabetes;

• asthma, chronic obstructive pulmonary disease (COPD), sleep apnea, or other breathing disorder;

• an intestinal disorder or obstruction;

• Gilbert's syndrome;

• fructose intolerance (Camptosar contains sorbitol); or

• if you are receiving radiation treatment to your abdomen or pelvic area.

Do not use Camptosar if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment.

It is not known whether irinotecan passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using Camptosar.

Before you are treated with Camptosar, tell your doctor about all other cancer medicines you have recently used.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• nefazodone;

• St. John's wort;

• an antibiotic - clarithromycin, erythromycin, telithromycin;

• antifungal medicine - itraconazole, ketoconazole, voriconazole;

• seizure medicine - carbamazepine, fosphenytoin, oxcarbazepine, phenobarbital, phenytoin, primidone; or

• antiviral medicine to treat hepatitis or HIV/AIDS - atazanavir, boceprevir, cobicistat (Stribild, Tybost), delavirdine, efavirenz, fosamprenavir, indinavir, nelfinavir, nevirapine, ritonavir, saquinavir, telaprevir.

This list is not complete. Other drugs may interact with irinotecan, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.