Eribulin, marketed under the brand name Halaven, is a chemotherapy medication used in the treatment of certain types of cancer. It is specifically indicated for the treatment of metastatic breast cancer in patients who have previously received at least two chemotherapeutic regimens for advanced disease. Eribulin is derived from a natural product called halichondrin B, which is isolated from certain marine sponges.

Eribulin works by interfering with microtubule dynamics, which are essential for cell division. Microtubules are protein structures involved in various cellular processes, including the separation of chromosomes during cell division. By disrupting microtubule dynamics, eribulin prevents cancer cells from dividing and proliferating, ultimately leading to cell death.

Eribulin (Halaven) is a non-taxane microtubule inhibitor - a chemotherapeutic anti-cancer drug that has been approved for the treatment of advanced metastatic breast cancer.

Eribulin Uses:

• Breast cancer, metastatic:
  • Treatment of metastatic breast cancer in patients who were treated with a minimum of 2 chemotherapy regimens containing anthracycline and taxane.
• Liposarcoma, unresectable, or metastatic:
  • Treatment of inoperable or metastatic liposarcoma in patients who have been treated before with an anthracycline-containing regime.

Eribulin (Halaven) Dose in Adults

Note: International Considerations:

• Some products may have vial strength and dosing expressed as the base (instead of as the salt).
• Refer to prescribing information for specific dosing information.

Eribulin (Halaven) Dose in the treatment of metastatic Breast cancer:

For treating breast cancer that has spread to other parts of the body, eribulin (called "Eribulin mesylate") is usually given like this:

• The medicine is given directly into the vein.
• The dose is 1.4 mg for every square meter of the person's body surface area.
• It's given on the first day and then again on the 8th day of a 21-day treatment period.

So, a patient would get the medicine on day 1 and day 8, and then they would have a break until the next 21-day period starts.

Eribulin (Halaven) Dose in the treatment of unresectable or metastatic liposarcoma: 

For treating Liposarcoma (a type of cancer) that can't be removed by surgery or has spread to other parts of the body:

• Eribulin (under the name "Eribulin mesylate") is given directly into the vein.
• The dose is 1.4 mg for every square meter of the person's body surface area.
• The medicine is given on day 1 and then again on day 8 of a 21-day cycle.

This means a patient gets the medicine on the first day, then on the 8th day, and then there's a break until the next 21-day period begins.

Use in Children:

Not indicated

Eribulin Pregnancy Category: D

• Eribulin might cause problems during pregnancy.
• Animal studies have shown it can affect the baby's development.
• Since eribulin is used to treat cancer, it can likely harm a baby if a woman takes it while she's pregnant.
• Women who can become pregnant should use reliable birth control during treatment with eribulin and for at least 2 weeks after the last dose.
• Men taking eribulin, who have partners that can become pregnant, should also use reliable birth control during treatment and for 3.5 months after the last dose.
• In Canada, the guidelines suggest women use birth control during eribulin treatment and for at least 3 months afterward.

Use while breastfeeding

• We're not sure if eribulin gets into breast milk.
• But, because it might cause serious problems for a baby who's breastfeeding, the company that makes the medicine says:
  • Don't breastfeed while taking eribulin.
  • Also, don't breastfeed for 2 weeks after you've had your last dose of eribulin.

Eribulin (Halaven) Dose in Kidney disease:

• If your kidneys are working well (CrCl is 50 mL/minute or more), you can take the normal dose of eribulin.
• If your kidneys are working a bit slower (CrCl is between 15 to 49 mL/minute), the dose should be lowered to 1.1 mg for every square meter of your body surface area.
• If you have really severe kidney problems, especially as described in Canada's guidelines, it's probably best not to use eribulin at all.

Eribulin (Halaven) Dose in Liver disease:

• If you have a mild liver problem (known as Child-Pugh class A): Take a lower dose of eribulin, which is 1.1 mg for every square meter of your body surface area.
• If you have a moderate liver problem (Child-Pugh class B): The dose should be even lower, at 0.7 mg for every square meter of your body surface area.
• If you have a severe liver problem (Child-Pugh class C): In the US, there's no clear guidance from the manufacturer on how much to take, because it hasn't been well-studied. But in Canada, the guidance suggests not using eribulin at all if you have this level of liver issue.

Common Side Effects of Eribulin (Halaven):

• Cardiovascular:
  • Peripheral Edema
• Central Nervous System:
  • Fatigue
  • Peripheral Neuropathy
  • Headache
• Dermatologic:
  • Alopecia
• Endocrine & Metabolic:
  • Hypokalemia
  • Hypocalcemia
  • Weight Loss
  • Hypophosphatemia
• Gastrointestinal:
  • Nausea
  • Constipation
  • Abdominal Pain
  • Anorexia
  • Decreased Appetite
  • Vomiting
  • Diarrhea
  • Stomatitis
• Genitourinary:
  • Urinary Tract Infection
• Hematologic & Oncologic:
  • Neutropenia
  • Anemia
• Hepatic:
  • Increased Serum ALT
  • Increased Serum AST
• Neuromuscular & Skeletal:
  • Weakness
  • Arthralgia
  • Myalgia
  • Back Pain
  • Ostealgia
  • Limb Pain
• Respiratory:
  • Cough
  • Dyspnea
• Miscellaneous:
  • Fever

Less Common Side Effects Of Eribulin (Halaven):

• Cardiovascular:
  • Hypotension
• Central Nervous System:
  • Anxiety
  • Depression
  • Dizziness
  • Insomnia
  • Myasthenia
• Dermatologic:
  • Skin Rash
• Endocrine & Metabolic:
  • Hyperglycemia
• Gastrointestinal:
  • Dysgeusia
  • Dyspepsia
  • Xerostomia
  • Mucosal Inflammation
• Hematologic & Oncologic:
  • Thrombocytopenia
  • Febrile Neutropenia
• Neuromuscular & Skeletal:
  • Muscle Spasm
  • Musculoskeletal Pain,
• Ophthalmic:
  • Increased Lacrimation
• Respiratory:
  • Oropharyngeal Pain
  • Upper Respiratory Tract Infection

Contraindications to Eribulin (Halaven):

• According to the company that makes the drug, there aren't any situations where you're specifically told not to take eribulin.
• However, in Canada, there's a warning: If you're allergic to eribulin, halichondrin B, or related chemicals, you shouldn't take it. This specific warning isn't mentioned in the US guidelines.

Warnings and precautions

Suppression of bone marrow

• Eribulin can cause issues with your blood, especially a decrease in a type of white blood cell called neutrophils. This can make you more prone to infections.
• Some people have had a severe drop in neutrophils, leading to a fever. There have even been some cases where this condition led to a severe, life-threatening infection.
• If these blood issues get severe, doctors might delay giving the drug or give a smaller dose.
• If a patient's liver tests (like ALT or AST) are much higher than normal or if their bilirubin (a liver enzyme) is high, they might be more likely to have these severe blood problems.
• Before each dose, doctors will check your blood to see how your cells are doing. If the cell counts are really low, they might check even more often.
• If you already had very low neutrophils (less than 1,500 in every tiny drop of blood) even before starting the drug, note that you weren't part of the group tested in the studies.

Peripheral neuropathy

• Eribulin can lead to issues with nerves, especially in your arms and legs (peripheral neuropathy).
• Peripheral neuropathy is common. For some people with metastatic breast cancer, it might last over a year. And in nearly 60% of liposarcoma patients, it can continue for more than 60 days. In one study, even after around 6 months, over 60% of liposarcoma patients still had neuropathy.
• For liposarcoma patients, it usually starts around 5 months after they begin treatment, but it can show up anytime between 3.5 to 9 months.
• Watch out for signs of numbness or tingling in your hands or feet. It might even affect your ability to move them.
• If this neuropathy becomes severe, doctors might stop the treatment for a while or altogether.
• Some patients already had nerve problems from previous chemotherapy. For them, it's important to keep an eye out for any worsening of these issues.

Extension of QT

• Eribulin can sometimes make the heartbeat in an unusual way, causing a delay in its rhythm. This is seen as a longer "QT interval" on an ECG (a test that measures the electric activity of the heart).
• In one study, this delay was noticed on the 8th day after starting eribulin.
• If a patient has heart problems, a naturally slow heart rhythm, is taking other medicines that can cause similar heart delays, or has imbalanced levels of certain body salts, they should have their heart's rhythm checked with an ECG.
• Before starting treatment, it's crucial to fix low levels of potassium (hypokalemia) and magnesium (hypomagnesemia). Keep checking these levels during the treatment.
• If someone was born with a condition where their heart naturally has this delay (called congenital long QT syndrome), they should probably avoid taking eribulin.

Hepatic impairment

• If you have mild to moderate liver issues (based on something called the Child-Pugh class A or B), you'll need a lower dose of eribulin.
• If you have severe liver problems, it's unknown how eribulin might affect you because it hasn't been tested in such cases.
• If your liver tests show increased levels of transaminase or bilirubin, you're more likely to face severe decreases in a type of white blood cell (called grade 4 neutropenia) and fever linked to this low cell count (neutropenic fever).

Renal impairment

• If you have moderate to severe kidney issues (measured as CrCl being 15 to 49 mL/minute), you'll need a lower dose of eribulin.

Monitoring parameters

Blood Tests:

• Check the complete blood count (CBC) with specifics on different cell types before each dose.
• If there are severe decreases in some cell counts (grades 3/4 cytopenias), do the blood tests more often.
• Check kidney and liver health.
• Measure levels of body salts, including potassium and magnesium.

Nerve Health:

• Before giving each dose, see if there are signs of peripheral neuropathy (like numbness or tingling in hands or feet).

Heart Health:

• Do an ECG (a heart test) for patients who:
  • Have heart failure.
  • Have a naturally slow heart rhythm (bradyarrhythmia).
  • Are on other meds that can affect the heart's rhythm.
  • Have low levels of certain body salts, like potassium and magnesium.

How to administer Eribulin (Halaven)?

Duration:

• Put it into the vein over a short time, between 2 to 5 minutes.

Dilution:

• You can give it as it is (undiluted) or mix it with some fluids (diluted).

Important Note:

• Don't give other medicines through the same IV line when giving eribulin.
• Don't use an IV line that has dextrose in it for eribulin.

Mechanism of action of Eribulin (Halaven):

• It's a medicine related to a natural substance called halichondrin B. It's different from some other cancer drugs called taxanes.
• Eribulin messes with the tiny structures in cells called microtubules.
• These structures help cells divide.
• Eribulin stops these microtubules from forming properly, which then blocks the cell from dividing.
• This causes the cell to get stuck at a specific phase, called the G/M phase, in its life cycle.
• Interestingly, while eribulin stops these microtubules from forming (polymerizing), it doesn't break them down (depolymerize).

Distribution:

• How much space the drug spreads through in the body: 43 to 114 liters per square meter of body.

Protein Binding:

• How much of the drug sticks to proteins in the blood: Between 49% to 65%.

Metabolism:

• How the body breaks the drug down: Barely at all (negligible).

Half-life:

• Time it takes for half of the drug to leave the body: Around 40 hours.

How it leaves the body:

• Through poop: About 82%, mostly without being changed.
• Through pee: About 9%, mostly in its original form.

International Brands of Eribulin:

• Halaven

Eribulin Brand Names in Pakistan:

Not available.