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Onivyde (Liposomal Irinotecan) - Uses, Dose, MOA, Side effects

Liposomal irinotecan is a form of the chemotherapy drug irinotecan that is encapsulated within liposomes, which are tiny lipid (fat) vesicles. Liposomal formulations are designed to improve the pharmacokinetics and therapeutic efficacy of drugs. Irinotecan itself is used to treat various types of cancer, particularly colorectal cancer.

Onivyde is a liposomal formulation of irinotecan that is used after gemcitabine, fluorouracil, and leucovorin for the treatment of metastatic pancreatic adenocarcinoma.

Liposomal Irinotecan Uses:

Metastatic pancreatic adenocarcinoma:
- Used in the management of metastatic adenocarcinoma of the pancreas.
- It should not be used as monotherapy. Utilized after gemcitabine therapy, along with fluorouracil and leucovorin.

Liposomal Irinotecan (Onivyde) Dose in Adults:

Note:

Liposomal irinotecan is a special version of a cancer drug, but it's different from the regular irinotecan.
Before getting this treatment, you'll need to take some medicines to prevent nausea, since this drug can make you feel sick.
It's important to know that the doses for the liposomal and regular versions are different.

Liposomal Irinotecan (Onivyde) Dose in the treatment of metastatic pancreatic adenocarcinoma:

For treating advanced pancreatic cancer, liposomal irinotecan is given through an IV drip at a dose of 70 mg for every square meter of body surface once every two weeks.
It's combined with two other medicines called fluorouracil and leucovorin.

Note: If a patient has a specific gene variation called UGT1A1*28, start with a lower dose of 50 mg for every square meter of body surface. If they handle it well, the dose can be raised to 70 mg in the next treatments.

Use in Children:

Not indicated.

Pregnancy Risk Category: D

Liposomal irinotecan might harm an unborn baby, based on how it works and tests on animals.
If a woman can get pregnant, she should use reliable birth control during treatment and for one month after the last dose.
Men should use condoms during treatment and for 4 months after their last dose if they're with women who can get pregnant.

Use while breastfeeding

We don't know if liposomal irinotecan is in breast milk.
But because it might harm a breastfeeding baby, the company that makes it advises not to breastfeed while taking the medicine and for one month after the last dose.

Dose in Kidney Disease:

For people with moderate kidney function (CrCl 30 to 89 mL/minute), the manufacturer's instructions don't mention any need to change the dosage. A study showed that this level of kidney function didn't affect the amount of the active ingredient in the body.
For those with lower kidney function (CrCl less than 30 mL/minute), the manufacturer's instructions don't provide information about changing the dosage because there isn't enough data available.

Dose in Liver disease:

If a person's bilirubin level is higher than the normal limit, the manufacturer doesn't give specific dosage changes. They also don't have a suggested dose, so it's best to be careful. There's no information about using this drug in people with bilirubin levels above 2 mg/dL.

Common Side Effects of Liposomal Irinotecan (Onivyde):

Frequency not always defined. Percentages reported as part of combination chemotherapy regimens.

Cardiovascular:
- Septic shock
Central nervous system:
- Fatigue
Dermatologic:
- Alopecia
Endocrine & Metabolic:
- Hypoalbuminemia
- Hypomagnesemia
- Hypocalcemia
- Hypokalemia
- Hypophosphatemia
- Hyponatremia
- Weight Loss
- Dehydration
Gastrointestinal:
- Diarrhea
- Vomiting
- Nausea
- Decreased Appetite
- Stomatitis
- Gastroenteritis
Hematologic & Oncologic:
- Anemia
- Lymphocytopenia
- Neutropenia
- Thrombocytopenia
- Febrile Neutropenia
Hepatic:
- Increased Serum ALT
Hypersensitivity:
- Severe Hypersensitivity
Infection:
- Sepsis
- Neutropenic Sepsis
Local:
- Catheter Infection
Neuromuscular & Skeletal:
- Weakness
Renal:
- Increased Creatinine Clearance
- Acute Renal Failure
Respiratory:
- Pneumonia
- Interstitial Pulmonary Disease
Miscellaneous:
- Fever

Contraindications to Liposomal Irinotecan (Onivyde):

If someone has a strong allergic reaction to liposomal irinotecan, irinotecan hydrochloride, or any part of the drug, they shouldn't take it.
In Canada, an additional reason not to use this drug, which isn't mentioned in the US instructions, is breastfeeding.

Warnings and precautions

Suppression of bone marrow: [US Boxed Warning]

Nearly 1% of patients who received irinotecan (liposomal) suffered from lethal neutropenic seizures.
Severe or life-threatening neutropenic fever or sepsis was reported in 3% of patients. In 20% of cases, severe or life-threatening neutropenia was observed in patients receiving irinotecan (liposomal), in combination with fluorouracil or leucovorin.
For absolute neutrophil count less than 1,500/mm, or for neutropenic fever, you should not use liposomal irinotecan.
During treatment, it is important to regularly check the blood cell countDay 1 through 8 of each cycle, and more frequently if clinically necessary.
You may need to stop treatment, reduce doses, or terminate the treatment.
Anemia, lymphopenia and thrombocytopenia are all common.
In Asian patients, neutropenia was more common than in white patients.

Gastrointestinal toxicities: [US Boxed Warning]

One third of patients who took irinotecan (liposomal), with fluorouracil, and leucovorin developed severe diarrhea.
Patients with bowel obstruction should not be given irinotecan (liposomal).
For diarrhea of grade 2 or 4, withhold irinotecan.
For late diarrhea, take loperamide.
If you are not allergic to atropine, take it if you have severe diarrhea.
Early diarrhea can occur within the first days of chemotherapy.
Late diarrhea can occur more than one day after chemotherapy.
Diarrhea can require medication interruption, dosage reduction and/or discontinuation.
Irinotecan (liposomal), is associated with mild emetic perspectives; antiemetics can be used to prevent nausea or vomiting.
Stomatitis is also a common condition.

Hypersensitivity reactions

Irinotecan (conventional) has been linked to serious allergic reactions, including anaphylaxis.
If severe hypersensitivity develops, monitor closely and stop using irinotecan (liposomal).

Toxicity in the lungs:

Irinotecan (conventional), can cause serious and severe interstitial lung disease.
If you experience new or progressive dyspnea or cough during diagnostic evaluation, stop using irinotecan liposomal.
If ILD diagnosis is confirmed, stop treatment.

Bowel obstruction

Patients suffering from bowel obstruction should avoid taking.

Hepatic impairment

Patients with hepatic disease have not been able to evaluate the pharmacokinetics and safety of irinotecan (liposomal).
Patients with hepatic issues receiving irinotecan (conventional) may have an increased risk of being exposed to the active metabolite (SN38). Toxicities could be higher.

Liposomal Irinotecan: Drug Interaction

Risk Factor C (Monitor therapy)
Aprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Bosentan	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Chloramphenicol (Ophthalmic)	May enhance the adverse/toxic effect of Myelosuppressive Agents.
Clofazimine	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CloZAPine	Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased.
Coccidioides immitis Skin Test	Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.
CYP3A4 Inducers (Moderate)	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
CYP3A4 Inhibitors (Moderate)	May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors).
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Denosumab	May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
Duvelisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Eltrombopag	May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates.
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Erdafitinib	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Fosaprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fosnetupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Gemfibrozil	May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. See separate drug interaction monographs for agents listed as exceptions.
Ivosidenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Larotrectinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Mesalamine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Netupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
Palbociclib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
P-glycoprotein/ABCB1 Inhibitors	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.).
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Ranolazine	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Rifabutin	May decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. Rifabutin may decrease the serum concentration of Irinotecan Products.
Rifapentine	May decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. Rifapentine may decrease the serum concentration of Irinotecan Products.
Sarilumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Simeprevir	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Smallpox and Monkeypox Vaccine (Live)	Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live).
Teriflunomide	May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates.
Tertomotide	Immunosuppressants may diminish the therapeutic effect of Tertomotide.
Tobacco (Smoked)	May decrease serum concentrations of the active metabolite(s) of Irinotecan Products.
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Trastuzumab	May enhance the neutropenic effect of Immunosuppressants.
Risk Factor D (Consider therapy modification)
Baricitinib	Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted.
Dabrafenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
Deferiprone	Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely.
Echinacea	May diminish the therapeutic effect of Immunosuppressants.
Fingolimod	Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections).
Leflunomide	Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly.
Lenograstim	Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy.
Lipegfilgrastim	Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy.
Lorlatinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.
Nivolumab	Immunosuppressants may diminish the therapeutic effect of Nivolumab.
Palifermin	May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy.
Roflumilast	May enhance the immunosuppressive effect of Immunosuppressants.
Sipuleucel-T	Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy.
Stiripentol	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring.
Tofacitinib	Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants.
Tolvaptan	May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates.
Vaccines (Inactivated)	Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation.
Risk Factor X (Avoid combination)
BCG (Intravesical)	Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical).
BCG (Intravesical)	Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical).
Cladribine	May enhance the immunosuppressive effect of Immunosuppressants.
Cladribine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Conivaptan	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CYP3A4 Inducers (Strong)	May decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be reduced. CYP3A4 Inducers (Strong) may decrease the serum concentration of Irinotecan Products.
CYP3A4 Inhibitors (Strong)	May increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, serum concentrations of SN-38 may be increased. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Irinotecan Products.
Dipyrone	May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
Fusidic Acid (Systemic)	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Idelalisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Lasmiditan	May increase the serum concentration of P-glycoprotein/ABCB1 Substrates.
Natalizumab	Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased.
Pimecrolimus	May enhance the adverse/toxic effect of Immunosuppressants.
St John's Wort	May decrease serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, concentrations of SN-38 may be reduced. St John's Wort may decrease the serum concentration of Irinotecan Products.
Tacrolimus (Topical)	May enhance the adverse/toxic effect of Immunosuppressants.
UGT1A1 Inhibitors	May increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, concentrations of SN-38 may be increased. UGT1A1 Inhibitors may increase the serum concentration of Irinotecan Products. Exceptions: Atazanavir; Ombitasvir, Paritaprevir, and Ritonavir; Ombitasvir, Paritaprevir, Ritonavir, and Dasabuvir.
Upadacitinib	Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib.
Vaccines (Live)	Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live).

Monitoring parameters:

Blood Counts

Check on day 1 and day 8 of each treatment cycle.
Check as needed based on the patient's condition.

Liver Function

Test bilirubin levels, especially if there's severe diarrhea.

Electrolytes

Check if someone has severe diarrhea.

Bowel Movements

Note how often someone has diarrhea and how severe it is.

Hydration Status

See if the patient is drinking enough water or if they're dehydrated.

Look Out for Specific Symptoms

Watch for signs of lung problems (pulmonary toxicity).
Be alert for allergic reactions (hypersensitivity reactions).

How to administer Liposomal Irinotecan (Onivyde)?

Nausea and Vomiting Prevention

This drug can make you feel sick. It's suggested to take medicines (antiemetics) to prevent nausea and vomiting.

How to Give the Drug

Use an IV drip to give the drug over 90 minutes.
30 minutes before giving the drug, give a corticosteroid and an anti-nausea medicine.
Always give irinotecan (liposomal) before giving fluorouracil and leucovorin.
Don't use filters when giving the drug through IV.

Dealing with Diarrhea

If diarrhea starts soon after treatment, give 0.25 to 1 mg of atropine through IV or under the skin, unless there's a reason not to.
For diarrhea that begins later on, use loperamide.

Mechanism of action of Liposomal Irinotecan (Onivyde):

Irinotecan (liposomal) is a drug wrapped in a fatty layer.
It and its active part, called SN-38, attach to a specific DNA-protein mix in our cells.
This stops the DNA from fixing itself after it gets cut.
Because our cells can't mend these big breaks in the DNA, the cells end up dying, especially when they're trying to make more of themselves.
This stops cells from multiplying.

Distribution

It spreads out to a volume of 4.1 liters in the body.
95% of it stays wrapped in its fatty layer (liposome).

Binding to Proteins

Less than 1% sticks to proteins.

How it's Changed in the Body (Metabolism)

Mostly changed in the liver to an active part called SN-38.
Some is turned to inactive parts, but one can release more SN-38.
SN-38 is further changed by an enzyme. If you have a specific gene variation (found in 10% of North Americans), you'll have more SN-38.

How Long it Stays in the Body (Half-life)