Onivyde

>10%

Diarrhea, grades 1-4 (59%)

Fatigue/asthenia, grades 1-4 (56%)

Vomiting, grades 1-4 (52%)

Nausea, grades 1-4 (51%)

Decreased appetite, grades 1-4 (44%)

Late diarrhea, grades 1-4 (43%)

Stomatitis, grades 1-4 (32%)

Early diarrhea, grades 1-4 (30%)

Lymphopenia, grades 3-4 (27%)

Pyrexia, grades 1-4 (23%)

Fatigue/asthenia, grades 3-4 (21%)

Neutropenia, grades 3-4 (20%)

Weight loss, grades 1-4 (17%)

Alopecia, grades 1-4 (14%)

Diarrhea, grades 3-4 (13%)

Vomiting, grades 3-4 (11%)

1-10%

Early diarrhea, grades 3-4 (9%)

Nausea, grades 3-4 (8%)

Dehydration (4-8%)

Anemia, grades 3-4 (6%)

Increased ALT, grades 3-4 (6%)

Hyponatremia, grades 3-4 (5%)

Cholinergic reactions, other than diarrhea (4.5%)

Decreased appetite, grades 3-4 (4%)

Stomatitis, grades 3-4 (4%)

Hypophosphatemia, grades 3-4 (4%)

Late diarrhea, grades 3-4 (3%)

Sepsis (3-4%)

Neutropenic fever/neutropenic sepsis (3%)

Gastroenteritis (3%)

IV catheter-related infection (3%)

Infusion reactions (3%)

Pyrexia, grades 3-4 (2%)

Weight loss, grades 3-4 (2%)

Thrombocytopenia, grades 3-4 (2%)

Hypoalbuminemia, grades 3-4 (2%)

Hypokalemia, grades 3-4 (2%)

Hypocalcemia, grades 3-4 (1%)

Alopecia, grades 3-4 (1%)

Black Box Warnings

Neutropenic sepsis

• Fatal neutropenic sepsis occurred in 0.8% of patients receiving irinotecan liposomal
• Severe or life-threatening neutropenic fever or sepsis occurred in 3% and severe or life-threatening neutropenia occurred in 20% of patients receiving irinotecan liposomal in combination with fluorouracil and leucovorin
• Withhold drug for absolute neutrophil count <1500/mm³ or neutropenic fever
• Monitor blood cell counts periodically during treatment

Diarrhea

• Severe diarrhea occurred in 13% of patients receiving irinotecan liposomal in combination with fluorouracil and leucovorin
• Do not administer to patients with bowel obstruction
• Withhold for diarrhea of grade 2-4 severity (see Dosage Modifications)
• Administer loperamide for late-onset diarrhea of any severity
• Administer atropine, if not contraindicated, for early-onset diarrhea of any severity

Contraindications

Hypersensitivity

Cautions

Can cause severe or life-threatening neutropenia and fatal neutropenic sepsis (see Black Box Warnings)

Can cause severe and life-threatening diarrhea; do not administer to patients with bowel obstruction (see Black Box Warnings)

Can cause severe and fatal interstitial lung disease; withhold drug in patients with new or progressive dyspnea, cough, and fever, pending diagnostic evaluation

Severe hypersensitivity reactions may occur, including anaphylaxis; permanently discontinue if a severe hypersensitivity reaction occurs

Based on animal data with irinotecan HCl and the mechanism of action of irinotecan liposomal, can cause fetal harm when administered to a pregnant woman (see Pregnancy)

Strong CYP3A4 inducers are known to substantially decrease systemic exposure to irinotecan or its active metabolite, SN-38

Strong CYP3A4 or UGT1A1 inhibitors have shown to increase systemic exposure to irinotecan or its active metabolite, SN-38

Pregnancy

Based on animal data with irinotecan HCl and the mechanism of action of irinotecan liposomal, can cause fetal harm when administered to a pregnant woman

Advise females of reproductive potential to use effective contraception during treatment and for 1 month after the final dose

Embryotoxicity and teratogenicity were observed following treatment with irinotecan HCl, at doses resulting in irinotecan exposures lower than those achieved with irinotecan liposomal 70 mg/m² in humans, when administered to pregnant rats and rabbits during organogenesis

Male reproductive recommendations

• Because of the potential for genotoxicity, advise males with female partners of reproductive potential to use condoms during treatment and for 4 months after the final dose

Lactation

Unknown if distributed in human breast milk

Because of the potential for serious adverse reactions in breastfed infants from irinotecan liposomal, advise a nursing woman not to breastfeed during treatment with and for 1 month after the final dose

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Irinotecan liposomal is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

Irinotecan liposomal is used to treat pancreatic cancer that has spread to other parts of the body.

Irinotecan liposomal is usually given in combination with other cancer medicines.

Irinotecan liposomal may also be used for purposes not listed in this medication guide.

Serious and sometimes fatal infections may occur during treatment with this medicine. Seek medical attention right away if you have signs of infection such as: sudden weakness or ill feeling, fever, chills, confusion, shortness of breath, rapid heart rate, and severe dizziness or fainting.

Irinotecan liposomal can cause severe diarrhea, which can be life-threatening if it leads to dehydration. Call your doctor whenever you have diarrhea during your treatment with this medicine.

You should not be treated with this medicine if you are allergic to irinotecan (Onivyde or Camptosar), or if you have:

• a bowel obstruction.

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

• liver or kidney disease;
• asthma, chronic obstructive pulmonary disease (COPD), or other breathing disorder;
• diabetes; or
• an intestinal disorder.

This medicine can harm an unborn baby or cause birth defects. Do not use if you are pregnant, and tell your doctor right away if you become pregnant. Use effective birth control while you are using this medicine and for at least 1 month after your treatment ends.

A man using irinotecan liposomal should use a condom during treatment, and for at least 4 months after treatment ends.

It is not known whether irinotecan liposomal passes into breast milk or if it could harm a nursing baby. Do not breast-feed while you are using this medicine, and for at least 1 month after your last dose.

Tell your doctor if you are pregnant or plan to become pregnant.

Based on animal data, Onivyde may cause harm to the unborn baby when given to a pregnant woman. Females of reproductive age should use an effective form of contraception during and for 1 month after Onivyde treatment.  

Males with females reproductive age should use condoms during treatment with Onivyde and for 4 months after the final dose of Onivyde.

You should not be treated with this medicine if you are allergic to irinotecan (Onivyde or Camptosar), or if you have:

• a bowel obstruction.

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

• liver or kidney disease;

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

• diabetes; or

• an intestinal disorder.

This medicine can harm an unborn baby or cause birth defects. Do not use if you are pregnant, and tell your doctor right away if you become pregnant. Use effective birth control while you are using this medicine and for at least 1 month after your treatment ends.

A man using irinotecan liposomal should use a condom during treatment, and for at least 4 months after treatment ends.

It is not known whether irinotecan liposomal passes into breast milk or if it could harm a nursing baby. Do not breast-feed while you are using this medicine, and for at least 1 month after your last dose.

Before you are treated with irinotecan liposomal, 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:

• gemfibrozil;

• nefazodone;

• St. John's wort;

• an antibiotic--clarithromycin, erythromycin, telithromycin;

• antifungal medicine--itraconazole, ketoconazole, voriconazole;

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

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

• tuberculosis medicine--rifabutin, rifapentine, rifampin.

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

• It is used to treat pancreatic cancer.

Use Onivyde as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.
• Other drugs may be given before this medicine to help avoid side effects.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of infection like fever, chills, very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, or wound that will not heal.
• Signs of fluid and electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or very bad upset stomach or throwing up.
• Signs of kidney problems like unable to pass urine, change in how much urine is passed, blood in the urine, or a big weight gain.
• Very upset stomach or throwing up.
• Any unexplained bruising or bleeding.
• Feeling very tired or weak.
• Very loose stools (diarrhea).
• Loose stools (diarrhea) that will not go away.
• Black, tarry, or bloody stools.
• Very bad and sometimes deadly lung problems have happened with Onivyde. Call your doctor right away if you have lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse.

Onivyde is formulated with irinotecan hydrochloride trihydrate, a topoisomerase inhibitor, into a liposomal dispersion for intravenous use. The chemical name of irinotecan hydrochloride trihydrate is (S)-4,11-diethyl-3,4,12,14-tetrahydro-4-hydroxy-3,14-dioxo1H-pyrano[3',4':6,7]-indolizino[1,2-b]quinolin-9-yl-[1,4'bipiperidine]-1'-carboxylate, monohydrochloride, trihydrate. The empirical formula is C33H38N4O6∙HCl∙3H2O and the molecular weight is 677.19 g/mole. The molecular structure is:

Onivyde is a sterile, white to slightly yellow opaque isotonic liposomal dispersion. Each 10 mL single-dose vial contains 43 mg irinotecan free base at a concentration of 4.3 mg/mL. The liposome is a unilamellar lipid bilayer vesicle, approximately 110 nm in diameter, which encapsulates an aqueous space containing irinotecan in a gelated or precipitated state as the sucrose octasulfate salt. The vesicle is composed of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) 6.81 mg/mL, cholesterol 2.22 mg/mL, and methoxy-terminated polyethylene glycol (MW 2000)-distearoylphosphatidyl ethanolamine (MPEG-2000-DSPE) 0.12 mg/mL. Each mL also contains 2-[4-(2-hydroxyethyl) piperazin-1-yl]ethanesulfonic acid (HEPES) as a buffer 4.05 mg/mL and sodium chloride as an isotonicity reagent 8.42 mg/mL.

How Supplied

Onivyde is available in a single-dose vial containing 43 mg irinotecan free base at a concentration of 4.3 mg/mL

NDC: 15054-0043-1

Storage and Handling

Store Onivyde at 2°C to 8°C (36°F to 46°F). Do NOT freeze. Protect from light.

Onivyde is a cytotoxic drug. Follow applicable special handling and disposal procedures.1

Advise patients of the following:

Severe Neutropenia

Advise patients of the risk of neutropenia leading to severe and life-threatening infections and the need for monitoring of blood counts. Instruct patients to contact their healthcare provider immediately if experiencing signs of infection, such as fever, chills, dizziness, or shortness of breath [see Warnings and Precautions (5.1)].

Severe Diarrhea

Inform patients of the risk of severe diarrhea. Advise patients to contact their healthcare provider if they experience persistent vomiting or diarrhea; black or bloody stools; or symptoms of dehydration such as lightheadedness, dizziness, or faintness [see Warnings and Precautions (5.2)].

Interstitial Lung Disease

Inform patients of the potential risk of ILD. Advise patients to contact their healthcare provider as soon as possible for new onset cough or dyspnea [see Interstitial Lung Disease (5.3)].

Hypersensitivity to irinotecan HCl or Onivyde

Advise patients of the potential risk of severe hypersensitivity and that Onivyde is contraindicated in patients with a history of severe allergic reactions with irinotecan HCl or Onivyde. Instruct patients to seek immediate medical attention for signs of severe hypersensitivity reaction such as chest tightness; shortness of breath; wheezing; dizziness or faintness; or swelling of the face, eyelids, or lips [see Contraindications (4) and Warnings and Precautions (5.4)].

Females and males of reproductive potential

Embryo-fetal toxicity: Inform females of reproductive potential of the potential risk to a fetus, to use effective contraception during treatment and for one month after the final dose, and to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.5), Use in Specific Populations (8.1, 8.3)].

Contraception: Advise male patients with female partners of reproductive potential to use condoms during treatment with Onivyde and for four months after the final dose [see Females and Males of Reproductive Potential (8.3)].

Lactation

Advise women not to breastfeed during treatment with Onivyde and for one month after the final dose [see Use in Special Populations (8.2)].

Manufactured for:

Ipsen Biopharmaceuticals, Inc.Basking Ridge, NJ 07920

Onivyde is a registered trademark of Ipsen Biopharm Ltd.