Vincristine is an anti-cancer (antineoplastic or cytotoxic) chemotherapy drug, which belongs to the group of drugs called vinca alkaloids. It's commonly used in the treatment of various types of cancers, including acute lymphoblastic leukemia, Hodgkin's disease, and non-Hodgkin's lymphoma, among others.

Liposomal formulations are a way of packaging drugs inside lipid-based nanoparticles (liposomes) to improve their delivery to targeted tissues and potentially reduce side effects. The primary goal of liposomal formulations is to increase the therapeutic index of drugs.

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:

• Vincristine is a medicine used to treat cancer.
• It's usually given through a vein in the body.
• There's a special type of vincristine called "liposomal vincristine." This special kind is not the same as the regular one.
• The way you give it and the amount you give are different.
• When using liposomal vincristine, the dose is based on the size of the person's body and is not limited to a certain amount.
• This is different from the regular kind of vincristine.
• It's very important to make sure you're using the right kind of vincristine and giving the correct amount.

Marqibo (Liposomal Vincristine) Dose in the treatment of Relapsed Acute lymphoblastic leukemia (Philadelphia chromosome-negative):

• The way to give this medicine is through a vein (intravenously or IV).
• Give a dose of 2.25 milligrams for each square meter of the person's body size.
• This dose is given once every 7 days.
• This treatment is used to fight the cancer and help the patient get better.

Use in Children:

The safety and efficacy of the drug in children have not been established.

Pregnancy Risk Category: D

• The way liposomal vincristine works and tests from studies on animals show that if an unborn baby (fetus) is exposed to this drug, it might get hurt.
• So, women who can get pregnant should make sure they don't get pregnant while getting this treatment.
• It's important to be cautious and take steps to prevent pregnancy during this time.

Use of lipoma vincristine during breastfeeding

• We're not sure if liposomal vincristine appears in breast milk.
• Since it might have negative effects on a baby that's breastfed, moms need to think about whether to stop breastfeeding or stop using liposomal vincristine.
• The choice should consider how helpful the treatment is for the mother's health.
• It's about balancing the benefits and possible risks to the baby.

Marqibo (Liposomal Vincristine) Dose in Kidney Disease:

• The company that makes liposomal vincristine hasn't given any guidelines on changing the dose for patients with kidney problems.
• This is because the drug doesn't pass out of the body much through the kidneys.
• So, just like the regular type of vincristine, patients with kidney issues probably don't need a different dose.

Marqibo (Liposomal Vincristine) Dose in Liver disease:

Before starting treatment with liver issues:

• Moderate liver problems (Child-Pugh class B):
  • In a study done on some skin cancer patients who had moderate liver issues due to cancer spreading to the liver, the drug worked similarly to those with a healthy liver. Patients with these liver problems were given a dose of 1 mg/m every 2 weeks, while patients with a healthy liver were given a dose of 2 mg/m.
• Severe liver problems (Child-Pugh class C):
  • The company that makes the drug hasn't given any advice on how much to give to patients with severe liver issues. They haven't studied this yet.

If liver issues happen during treatment: Reduce the amount of the drug given or pause the treatment for a while.

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):

People should NOT use liposomal vincristine if:

• They are allergic to vincristine, the special version called liposomal vincristine, or any ingredient in the medicine.
• They have a disease called Charcot-Marie-Tooth syndrome or other conditions where the protective cover of their nerves is damaged.
• The medicine is being given directly into the spinal fluid.

Warnings and precautions

Suppression of bone marrow

• Serious issues with low white blood cells, red blood cells, and platelets were seen in some tests.
• It's important to frequently check the patient's blood.
• If the counts are too low, the medicine dose might need to be changed or even stopped for a bit.

Constipation

• Liposomal vincristine can lead to constipation, which might even cause problems like bowel blockage.
• To prevent this, patients should start a plan that includes things like softening their stool, eating more fiber, and staying hydrated.
• They might also need to use laxatives to help with this issue.

Fatigue

• People in the tests felt really tired when they took liposomal vincristine.
• If this happens, they might need to wait a bit before their next dose, take less of the medicine, or stop it altogether.

Hepatotoxicity

• Some people have had liver damage, and there have been deadly cases, after taking liposomal vincristine. There's also been an increase in a liver test called AST.
• Doctors should check the liver with tests often. If there are problems, the drug amount might need to be reduced, or the treatment may need to be paused.
• Be careful when giving this drug to people with liver problems. The regular form of vincristine is processed a lot by the liver. The liposomal form hasn't been thoroughly studied in people with severe liver issues.
• In one study, skin cancer patients with medium-level liver problems, mainly because cancer had spread to the liver, were given liposomal vincristine. The way their bodies handled the drug was similar to people with healthy livers. But, the dose they got was smaller (1 mg/m every 2 weeks) compared to people with healthy livers (2 mg/m).

Neurotoxicity:

• Taking liposomal vincristine can lead to nerve problems that get worse over time.
• Symptoms of these nerve problems might be feelings of tingling, numbness, reduced reflexes, nerve pain, pain in the jaw, problems with nerves in the head, bowel issues due to nerve problems, joint pain, muscle pain, muscle cramps, and/or feeling weak.
• Before giving someone liposomal vincristine, check their nerve health carefully. The risk of nerve problems is even higher for those who already have issues with their nerves or muscles, or when the drug is taken with other drugs that can hurt the nerves.
• If someone shows signs of these nerve problems, you might need to delay the treatment, adjust the drug amount, or even stop the treatment.

Tumor lysis syndrome

• Taking liposomal vincristine might cause a condition where cancer cells break down quickly, releasing their contents into the bloodstream. This is called tumor lysis syndrome.
• Keep a close eye on patients for signs of this happening. If it does, you'll need to treat it right away.

Liposomal Vincristine: Drug Interaction

Monitoring parameters:

Blood Tests

• Full blood count (checks white cells, red cells, and platelets)
• Liver function tests (to see how well the liver is working)

Nerve Health

• Watch out for signs or symptoms of nerve damage or other nerve-related issues.

Salt Levels (For older patients)

• Check sodium levels. Regular vincristine can lead to low sodium or cause problems related to the wrong release of a hormone that controls water and salt balance.

Tumor Cell Breakdown

• Look for signs/symptoms that indicate the quick breakdown of cancer cells (tumor lysis syndrome).

Bowel Movements

• Monitor for signs of constipation.

Infusion Site

• Check the spot where the medicine is given into the vein to make sure there's no leakage or damage.

How to administer Marqibo (Liposomal Vincristine)?

• Route of Administration
  • Only give through IV (in the vein).
  • It can be deadly if given in any other way.
• Special Precautions
  • Never give liposomal vincristine at the same time as medicines meant for the brain and spinal cord.
• How to Administer
  • Let it flow into the vein over 1 hour.
  • Don't give it quickly or all at once.
  • Don't use special in-line filters when giving it.
  • Don't give it with other medicines.
  • Finish the infusion within 12 hours after preparing the medicine.
• Potential Risks
  • Regular vincristine can cause skin and tissue damage if it leaks out of the vein.
  • We don't know much about the effects if liposomal vincristine leaks, but it might cause swelling and irritation.
  • So, make sure it doesn't leak out (avoid extravasation).

Mechanism of action of Marqibo (Liposomal Vincristine):

• The liposomal version of vincristine stays in the body longer, which makes it better at fighting cancer cells.
• This is because it has a longer "half-life," meaning it sticks around for a while.
• The liposomal form of vincristine is made up of tiny structures called "sphingosomes." These are like tiny packages made of sphingomyelin and cholesterol.
• The vincristine is inside these packages.
• When they get to the tumor cells, they release the vincristine, which helps kill the cancer cells more effectively.
• This formulation is designed to work better against the cancer cells.

Distribution:

• The volume in which liposomal vincristine spreads in the body is about 2.7 liters.

Metabolism:

• The liver is mainly responsible for processing liposomal vincristine.

Half-life Elimination:

• It takes about 45 hours for half of the liposomal vincristine to leave the body through urine. This time can vary based on how quickly the vincristine is released from the sphingosomes.

Excretion:

• Most of the liposomal vincristine is eliminated through the feces (around 69%), and only a small amount through the urine (less than 8%).

International Brands of Liposomal vincristine:

• Marqibo

Liposomal vincristine Brand Names in Pakistan:

Not Available.