Novaplus Irinotecan Hydrochloride (Intravenous)

Irinotecan injection is used along with other medicines (such as 5-fluorouracil and leucovorin) to treat patients with metastatic cancer (cancer that has spread) of the colon or rectum. It is also given to patients with metastatic colon or rectal cancer whose disease has progressed or come back after treatment with fluorouracil.

Irinotecan is part of a group of medicines called antineoplastics (cancer medicines). It works by interfering with the growth of cancer cells, which are eventually destroyed. Normal cells may also be affected by this medicine, leading to other effects. Some of these effects may be serious and need to be reported to your doctor. Other effects, like hair loss, may not be serious but could still be concerning. Some effects may happen after you stop taking irinotecan. Make sure you have discussed with your doctor the possible side effects of this medicine along with its benefits.

This medicine should only be given by or under the direct supervision of your doctor.

It is very important that your doctor checks your progress at regular visits to ensure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to prevent pregnancy during treatment and for at least 6 months after your last dose. Males using this medicine with female partners who can become pregnant must use effective birth control during and for at least 3 months after the last dose of this medicine. If you think you have become pregnant while using the medicine, tell your doctor right away.

This medicine may cause a serious allergic reaction called anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have chills, fever, hives, hoarseness, itching, rash, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth after you receive the medicine.

Irinotecan may cause diarrhea, which can last long enough and be severe enough to cause serious medical problems. If diarrhea occurs while you are being treated with irinotecan:

• Check with your doctor immediately. Be sure to let your doctor know if the diarrhea started during an irinotecan injection or less than 24 hours afterwards. Also, be sure to tell your doctor if you had any other symptoms, such as stomach cramps or sweating, before the diarrhea started. This means that you are having a certain kind of diarrhea that may need to be treated by your doctor.
• If diarrhea first occurs more than 24 hours after a dose of irinotecan, start taking loperamide (Imodium A-D®) as soon as you notice that your bowel movements are happening more often or are looser than usual. Loperamide is available without a prescription. Buy some of it ahead of time, so that you will have it on hand in case it is needed. Unless otherwise directed by your doctor, take 4 milligrams (mg) of loperamide (2 capsules or tablets, or 4 teaspoonfuls of the oral solution dosage form) for the first dose, then 2 mg (1 capsule or tablet, or 2 teaspoonfuls of the oral solution dosage form) every 2 hours. To interrupt your sleep less often, you may take 4 mg of loperamide every 4 hours during the night. Continue taking loperamide, day and night, until you have not had any diarrhea for 12 hours. It is very important that you follow these (or your doctor's) directions, even though they are different from the directions on the nonprescription (over-the-counter [OTC]) loperamide package label. The largest amount of loperamide recommended on the package label for use in a 24-hour period (8 mg) is not enough for treating diarrhea caused by irinotecan. Notify your doctor if the diarrhea is not controlled within 24 hours.
• Diarrhea causes loss of body fluid, which can lead to dehydration, a serious medical problem. To prevent this, it is very important that you replace the lost fluid. While you have diarrhea, and for a day or two after the diarrhea has stopped, drink plenty of clear liquids, such as ginger ale, caffeine-free cola, decaffeinated tea, and broth. Ask your doctor about the amount of liquid you should be drinking every day. Also, ask your doctor whether you should use a sports drink (e.g., Gatorade®), which contains other substances, such as sodium and potassium, that may be lost along with body fluid. Follow your doctor's directions very carefully.
• Because alcohol and caffeine can increase fluid loss, you should not drink beverages or take any medicines that contain them while you have diarrhea. Also, avoid eating foods that may make diarrhea worse, such as bran, raw fruits or vegetables, or fatty, fried, or spicy foods.
• Vomiting can also increase the amount of fluid lost by the body and increase the risk of dehydration. If vomiting occurs at the same time as diarrhea, check with your doctor right away.
• Signs of too much fluid loss (dehydration) include decreased urination, dizziness or light-headedness, dry mouth, fainting, increased thirst, and wrinkled skin. If any of these occur, check with your doctor immediately.

Irinotecan can temporarily lower the number of white blood cells in your blood, increasing the chance of getting an infection. It can also lower the number of platelets, which are needed for proper blood clotting. If this occurs, there are certain precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor immediately if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor immediately if you notice any unusual bleeding or bruising, black, tarry stools, blood in your urine or stools, or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Also, check with your doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail clippers.
• Avoid contact sports or other situations where bruising or injury could occur.

Call your doctor right away if you have an unexplained fever, cough, or trouble breathing after receiving this medicine. These may be symptoms of a serious lung problem.

This medicine may increase your risk of having blood clots. Tell your doctor right away if you start having a sudden and severe headache, trouble breathing, or problems with vision, speech, or walking.

This medicine may cause some people to feel dizzy, drowsy, or less alert than usual. This medicine may also cause blurred vision or other vision problems. If any of these side effects occur, do not drive, use machines, or do anything else that could be dangerous if you are not alert or able to see well. If these reactions are especially bothersome, check with your doctor.

If you plan to have children, talk with your doctor before using this medicine. Some men and women using this medicine have become infertile (unable to have children).

Ketoconazole (Nizoral®) and St. John's wort should not be used while you are receiving irinotecan. If you are using St. John's wort, it should be stopped at least 2 weeks before the first cycle of irinotecan. If you are using ketoconazole, it should be stopped at least 1 week before starting irinotecan treatment.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

In deciding to use a medicine, you and your doctor need to consider the risks of taking the medicine against the benefits it may provide. For this medicine, here are important points to think about:

Allergies

Inform your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also, let your healthcare professional know if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, carefully read the label or package ingredients.

Pediatric

There have not been appropriate studies on how irinotecan injection affects children. Safety and effectiveness have not been established for this age group.

Geriatric

Current studies have not shown any specific problems in older adults that would limit the usefulness of irinotecan injection. However, older patients are more likely to experience severe diarrhea, which may require caution and a dose adjustment for those receiving irinotecan.

Breast Feeding

There are no adequate studies in women to determine the risk to infants when using this medication while breastfeeding. Consider the potential benefits and risks before taking this medication during breastfeeding.

Interactions with Medicines

Some medicines should never be used together, while others may be used together with caution. Your doctor may need to adjust the dose or take other precautions. It is very important for your healthcare professional to know if you are taking any of the medicines listed below. The following interactions are significant and not necessarily an exhaustive list.

Using this medicine with any of the following medicines is not recommended. Your doctor may choose not to treat you with this medication or adjust your other medicines.

• Atazanavir
• Itraconazole
• Ketoconazole
• Measles Virus Vaccine, Live
• Mumps Virus Vaccine, Live
• Rotavirus Vaccine, Live
• Rubella Virus Vaccine, Live
• Varicella Virus Vaccine, Live
• Zoster Vaccine, Live

Using this medicine with any of the following medicines is usually not recommended but may be necessary in some situations. If both medicines are prescribed together, your doctor may change the dose or frequency of one or both medicines.

• Abametapir
• Adenovirus Vaccine
• Bacillus of Calmette and Guerin Vaccine, Live
• Boceprevir
• Capmatinib
• Carbamazepine
• Cholera Vaccine, Live
• Clarithromycin
• Cobicistat
• Conivaptan
• Darolutamide
• Darunavir
• Dengue Tetravalent Vaccine, Live
• Enasidenib
• Encorafenib
• Fedratinib
• Fexinidazole
• Fosnetupitant
• Fosphenytoin
• Idelalisib
• Indinavir
• Influenza Virus Vaccine, Live
• Leflunomide
• Leniolisib
• Lopinavir
• Mavacamten
• Midostaurin
• Momelotinib
• Nefazodone
• Nelfinavir
• Netupitant
• Omaveloxolone
• Phenobarbital
• Phenytoin
• Poliovirus Vaccine, Live
• Posaconazole
• Primidone
• Rifabutin
• Rifampin
• Rifapentine
• Ritonavir
• Saquinavir
• Smallpox Vaccine
• St John's Wort
• Tafamidis
• Telaprevir
• Telithromycin
• Teriflunomide
• Tipranavir
• Typhoid Vaccine, Live
• Voriconazole
• Yellow Fever Vaccine

Using this medicine with any of the following medicines may increase the risk of certain side effects, but using both drugs may be necessary for your treatment. If both medicines are prescribed together, your doctor may adjust the dose or frequency of one or both medicines.

• Citalopram
• Eltrombopag
• Rolapitant

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be taken around the time of eating food or specific types of food due to potential interactions. Alcohol or tobacco use with certain medicines may also lead to interactions. The following interactions are significant and not necessarily an exhaustive list.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or frequency of this medicine or provide special instructions regarding food, alcohol, or tobacco use.

• Grapefruit Juice
• Tobacco

Other Medical Problems

Other medical issues may affect how this medicine works. Make sure to inform your doctor if you have any other medical problems, especially:

• Bleeding problems or
• Kidney disease or
• Liver disease or
• Lung disease (e.g., interstitial pulmonary disease) or
• Severe diarrhea—Use with caution. May worsen these conditions.

• Severe bone marrow disease, or
• Bowel blockage or
• Gilbert's syndrome (an inherited disorder) or
• Neutropenia (low white blood cell count) or
• Reduced UGT1A1 activity (an enzyme issue)—May increase the risk of more serious side effects.

• Infection—May reduce your ability to fight infections.

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:

More common

• 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 or skin rash
• 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
• 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
• troubled breathing
• 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

Less common

• 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
• wrinkled skin

Rare

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

Incidence not known

• 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:

More common

• 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 the hands or bottoms of feet
• passing gas
• right upper abdominal or stomach pain and fullness
• sensation of spinning
• sleepiness or unusual drowsiness
• stomach discomfort, upset, or pain
• trouble sleeping
• weight loss

Incidence not known

• 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.

In the U.S.

• Camptosar
• Novaplus Irinotecan Hydrochloride

Available Dosage Forms:

• Solution

Therapeutic Class: Antineoplastic Agent

Pharmacologic Class: Topoisomerase I Inhibitor

A doctor or other trained health professional will give you this medicine in a hospital or cancer treatment center. This medicine is given through a needle placed in one of your veins.

Irinotecan often causes nausea and vomiting. However, it is very important that you continue to receive this medicine even if you begin to feel ill. You may receive other medicines to help with the nausea and vomiting. Ask your doctor for other ways to lessen these effects.

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