Marqibo is a liposomal formulation of vincristine (oncovin). It is a chemotherapeutic drug with a longer duration of action and hence a greater antitumor activity.
Marqibo (Liposomal Vincristine) Uses:
-
Relapsed Acute lymphoblastic leukemia:
- It is indicated for the treatment of adult patients with relapsed Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in second or greater relapse or those patients whose disease has progressed after two or more antileukemic therapies.
Marqibo (Liposomal Vincristine) Dose in Adults:
Note:
- Conventional and liposomal vincristine are NOT interchangeable.
- The dosing of the two formulations differ. The dose and formulation should be verified before the drug administration.
- The dose of liposomal vincristine is based on the actual body surface area.
Marqibo (Liposomal Vincristine) Dose in the treatment of Relapsed Acute lymphoblastic leukemia (Philadelphia chromosome-negative):
- 2.25 mg/m² intravenous once every week.
Use in Children:
The safety and efficacy of the drug in children have not been established.
Pregnancy Risk Category: D
- It can cause severe harm to the foetus in animal reproduction studies based on its mechanism.
- Effective contraception should be used during treatment for females with reproductive potential. This will help to avoid pregnancy.
Use of lipoma vincristine during breastfeeding
- It is unknown if the drug will be excreted into breastmilk.
- The manufacturer suggests that breastfeeding be stopped or the risk of adverse side effects for the infant.
Marqibo (Liposomal Vincristine) Dose in Kidney Disease:
- The manufacturer has not recommended any adjustments in the dose in patients with kidney impairment.
- However, dose adjustment is not required since the drug is minimally excreted via the kidneys.
Marqibo (Liposomal Vincristine) Dose in Liver disease:
-
Hepatic impairment prior to treatment initiation:
- Moderate impairment (Child-Pugh class B):
- Patients with moderate hepatic impairment may be given a reduced dose of 1 mg/m².
- Severe impairment (Child-Pugh class C):
- It has not been studied in severe hepatic impairment. Adjustments in the dose have not been provided in the manufacturer's labeling.
- There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
- Hepatotoxicity during treatment:
- Interrupt treatment or reduce the dose
- Moderate impairment (Child-Pugh class B):
Common Side Effects of Marqibo (Liposomal Vincristine):
-
Central nervous system:
- Fatigue
- Peripheral neuropathy
- Insomnia
-
Gastrointestinal:
- Constipation
- Nausea
- Diarrhea
- Decreased appetite
-
Hematologic & oncologic:
- Febrile neutropenia
- Anemia
- Neutropenia
- Thrombocytopenia
-
Hepatic:
- Increased serum AST
-
Miscellaneous:
- Fever
Less Common Side Effects of Marqibo (Liposomal Vincristine):
-
Cardiovascular:
- Hypotension
- Septic Shock
-
Central Nervous System:
- Pain
- Mental Status Changes
- Myasthenia
-
Gastrointestinal:
- Abdominal Pain
- Intestinal Obstruction
-
Infection:
- Staphylococcal Bacteremia
-
Neuromuscular & Skeletal:
- Weakness
-
Respiratory:
- Pneumonia
- Respiratory Distress
- Respiratory Failure
Contraindications to Marqibo (Liposomal Vincristine):
- Allergy to vincristine or liposomal vincristine or any component of this formulation
- Charcot-MarieTooth syndrome and other demyelinating disorders are common.
- Administration via the intrathecal route
Warnings and precautions
-
Suppression of bone marrow
- It is important to monitor blood counts and adjust the dose if hematologic toxicities have been detected.
- Some patients may experience anemia, thrombocytopenia or neutropenia (grades 3 and higher).
-
Constipation
- Use of liposomal vincristine has been linked to constipation, pseudo-ileus, bowel obstruction and ileus.
- Patients should be hydrated and given a stool softener. Patients may need an additional laxative.
-
Fatigue
- Some patients may feel fatigued and need to be treated.
-
Hepatotoxicity
- Patients receiving liposomal vincristine therapy have been known to suffer from fatal hepatotoxicity.
- It is important to regularly assess the liver's functions. Initial signs of hepatotoxicity include an increase in the AST.
- Although liver impairment has not been confirmed, the effects of liposomal vincristine have not been investigated.
- However, conventional vincristine undergoes extensive liver metabolism.
- The dose should be decreased in moderate hepatic impairment.
-
Neurotoxicity:
- The treatment may cause sensory or motor neuropathy.
- Dysaesthesia, hyporeflexia and areflexia can all be symptoms of neuropathic symptoms. Myalgias, muscle spasms and weakness may also be common.
- Before any treatment, a neurologic evaluation is required.
- Neurologic toxicities can be more common in patients with neuromuscular disease or those who are currently taking neurotoxic drugs.
- Neurotoxicity can lead to treatment interruptions, dose adjustments, or discontinuation.
-
Tumor lysis syndrome
- You should be aware of the clinical and laboratory signs and symptoms of tumor lysis syndrome, and take appropriate action.
Liposomal vincristine: Drug Interaction
|
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). |
|
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). |
|
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. |
|
MitoMYcin (Systemic) |
Antineoplastic Agents (Vinca Alkaloids) may enhance the adverse/toxic effect of MitoMYcin (Systemic). Specifically, the risk of pulmonary toxicity may be increased. |
|
Netupitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
NIFEdipine |
May increase the serum concentration of VinCRIStine (Liposomal). |
|
Ocrelizumab |
May enhance the immunosuppressive effect of Immunosuppressants. |
|
Palbociclib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Pidotimod |
Immunosuppressants may diminish the therapeutic effect of Pidotimod. |
|
Promazine |
May enhance the myelosuppressive effect of Myelosuppressive Agents. |
|
Rifabutin |
May decrease the serum concentration of VinCRIStine (Liposomal). |
|
Rifapentine |
May decrease the serum concentration of VinCRIStine (Liposomal). |
|
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). |
|
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). |
|
Teniposide |
May enhance the neurotoxic effect of VinCRIStine (Liposomal). |
|
Tertomotide |
Immunosuppressants may diminish the therapeutic effect of Tertomotide. |
|
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 |
|
|
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. |
|
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 the serum concentration of VinCRIStine (Liposomal). |
|
CYP3A4 Inhibitors (Strong) |
May increase the serum concentration of VinCRIStine (Liposomal). |
|
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. |
|
P-glycoprotein/ABCB1 Inducers |
May decrease the serum concentration of VinCRIStine (Liposomal). |
|
P-glycoprotein/ABCB1 Inhibitors |
May increase the serum concentration of VinCRIStine (Liposomal). |
|
Pimecrolimus |
May enhance the adverse/toxic effect of Immunosuppressants. |
|
St John's Wort |
May decrease the serum concentration of VinCRIStine (Liposomal). |
|
Tacrolimus (Topical) |
May enhance the adverse/toxic effect of Immunosuppressants. |
|
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 complete counts with differential and platelets
- Liver function tests
- Evaluate for the features of peripheral neuropathy or other neurologic toxicities
- Monitor sodium levels especially in the elderly patients (Patients may develop SIADH)
- Monitor for gastrointestinal symptoms (constipation, ileus, and intestinal obstruction)
- Monitor the clinical features of tumor lysis syndrome.
- Monitor the patient for infusion site reactions.
How to administer Marqibo (Liposomal Vincristine)?
- This medication is only available for intravenous administration.
- If administered through other routes, it can cause life-threatening reactions.
- This medication should not be used in conjunction with other CNS medications.
- You should administer the intravenous infusion for at least one hour.
- Avoid push administration or intravenous bolus.
- Avoid the use of in-line filters or concomitant administration of other medications.
- Within twelve hours of preparation, the infusion must be complete.
- Extravasation should be avoided as it can cause inflammation (conventional vincristine, a vesicant) Data regarding liposomal Vincristine extravasation are limited.
Mechanism of action of Marqibo (Liposomal Vincristine):
- The liposomal form of vincristine increases its half-life, enhancing its cytotoxic effect in tumor cells.
- The liposomal formulation contains vincristine, encapsulated within sphingosomes.
- Sphingosomes contain sphingomyelin, cholesterol.
- Vincristine blocks the formation of microtubules by binding to tubulin.
- This results in the arrest of the cell at metaphase and the disruption of the formation the mitotic spindle.
- The detailed mechanism of action is given here: https://emedz.net/vincristine-oncovin/
Metabolism:
- It is metabolized by the liver.
Half-life elimination:
- 45 hours (urinary half-life);
Excretion:
- Feces (69%);
- urine (<8%)
International Brands of Liposomal vincristine:
- Marqibo
Liposomal vincristine Brand Names in Pakistan:
No Brands Available in Pakistan.
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