Ellence (Epirubicin) is a cytotoxic or antineoplastic chemotherapeutic drug classified as "anthracycline anticancer antibiotic". It is indicated for the treatment of cancers including breast cancer as adjuvant chemotherapy.

Indications of Epirubicin (Ellence):

• Breast cancer (adjuvant treatment):
  • It is used as adjuvant therapy component for primary breast cancer in patients with evidence of axillary node involvement after tumor resection.
• Off Label Use of Epirubicin in Adults:
  • Esophageal cancer
  • Gastric cancer
  • Osteosarcoma
  • Soft tissue sarcoma

Epirubicin (Ellence) dose in adults:

Note:

• Prophylactic antibiotic therapy with sulfamethoxazole/trimethoprim or a fluoroquinolone should be given to patients receiving 120 mg/m²/cycle as part of combination therapy (CEF-120 regimen).
• Patients who are heavily pretreated, patients with preexisting myelosuppression, or with bone marrow involvement should be treated with the lower initial dose.
• Epirubicin therapy should be delayed until the clearance of other cardiotoxic agents with long half-lives (eg, trastuzumab).
• The recommended lifetime maximum dose is 900 mg/m².
• Antiemetics are recommended to prevent nausea and vomiting due to the high emetic potential of epirubicin.

Epirubicin (Ellence) dose in the treatment of Breast cancer (as adjuvant therapy):

• CEF-120 regimen:
  • Epirubicin is given at 60 mg/m^2 on the first and eighth days, every 28 days. This is repeated for 6 cycles. It's combined with two other drugs: cyclophosphamide and fluorouracil.
• FEC-100 regimen:
  • Epirubicin is given at 100 mg/m^2 on the first day, every 21 days. This goes on for 6 cycles. Again, it's mixed with cyclophosphamide and fluorouracil.

Other ways to use Epirubicin for Breast Cancer (not the standard way):

• EC regimen:
  • Epirubicin at 100 mg/m^2 on the first day, every 21 days. Do this for 8 cycles. It's combined with just one other drug: cyclophosphamide.
• EP or EC regimen:
  • Epirubicin at 75 mg/m^2 on the first day, every 21 days. Up to 6 cycles. It's used with either paclitaxel or cyclophosphamide.
• FEC regimen with or without paclitaxel:
  • Epirubicin at 90 mg/m^2 on the first day, every 21 days. 6 cycles if mixed with fluorouracil and cyclophosphamide. Or, 4 cycles with those drugs followed by paclitaxel.
• FEC then pertuzumab + trastuzumab + docetaxel regimen:
  • Epirubicin at 100 mg/m^2 on the first day, every 21 days. Do this for 3 cycles with fluorouracil and cyclophosphamide. After that, 3 cycles of three other drugs: pertuzumab, trastuzumab, and docetaxel.
• CEF regimen:
  • Epirubicin is given at 50 mg/m^2 on days 1 and 8. This can be every 21 or 28 days, and lasts for 6 to 9 cycles. It's used with cyclophosphamide and fluorouracil.

Note: These are different ways to use epirubicin based on research studies. The best regimen for someone depends on their health and the specifics of their cancer.

Epirubicin (Ellence) dose in the treatment of Esophageal cancer (off-label): IV:

Using ECF, ECX, EOF, or EOX regimens:

• Epirubicin is given at 50 mg/m^2 on the first day, every 21 days.
• This can be done for up to 8 cycles.
• In these treatments, epirubicin is combined with:
  • C: cisplatin
  • O: oxaliplatin
  • F: fluorouracil
  • X: capecitabine

Using the ECF regimen specifically:

• Epirubicin is given at 50 mg/m^2 on the first day, every 21 days.
• Patients receive 3 cycles before surgery and 3 cycles after surgery.
• For this treatment, epirubicin is mixed with:
  • cisplatin
  • fluorouracil

Note: "Off-label" means using the drug for a purpose that it's not officially approved for. Even if it's off-label, doctors sometimes do this based on new research or their experience.

Epirubicin (Ellence) dose in the treatment of Gastric cancer (off-label): 

Using ECF, ECX, EOF, or EOX regimens:

• Epirubicin is given at 50 mg/m^2 on the first day, every 21 days.
• This can last for up to 8 cycles.
• In these treatments, epirubicin is used with:
  • C: cisplatin
  • O: oxaliplatin
  • F: fluorouracil
  • X: capecitabine

Using the ECF regimen specifically:

• Epirubicin is given at 50 mg/m^2 on the first day, every 21 days.
• Patients get 3 cycles before surgery and 3 more cycles after the surgery.
• For this treatment, epirubicin is combined with:
  • cisplatin
  • fluorouracil

Remember, "off-label" means the drug is being used for a purpose that's not its primary approved use. It's always essential to consult with an oncologist or specialist to determine the most appropriate treatment plan for an individual.

Epirubicin (Ellence) dose in the treatment of Osteosarcoma (off-label use):

Epirubicin is given at 90 mg/m^2:

• Before surgery: Once every 21 days for 3 cycles.
• After surgery: Once every 28 days for 3 more cycles.

During this treatment, epirubicin is combined with:

• cisplatin
• ifosfamide
• mesna

This information is based on the Basaran 2007 study.

Ellence (Epirubicin) dose in the treatment of Soft tissue sarcoma (off-label):

Using the Petrioli 2002 regimen:

• Epirubicin is given at 25 mg/m^2 on days 1, 2, and 3 every 28 days.
• This is repeated for 4 cycles.
• Epirubicin is combined with:
  • ifosfamide
  • mesna

Using the Frustaci 2001 regimen:

• Epirubicin is given at 60 mg/m^2 on days 1 and 2 every 21 days.
• This continues for 5 cycles.
• Epirubicin is used with:
  • ifosfamide
  • mesna
  • filgrastim

These are off-label treatments, meaning they're not the standard approved use of the drug for this condition.

Use in Children:

Not indicated

Ellence (Epirubicin) Pregnancy Risk Factor D

• Studies with animals have shown that there can be problems during pregnancy if a woman takes epirubicin. So, if a woman could get pregnant, she should use effective birth control and avoid getting pregnant while taking this medication.
• Epirubicin might make some premenopausal women stop having their periods, and this might be permanent.
• There is limited information from studies on pregnant women who took epirubicin for cancer treatment during pregnancy.
• Some things about how epirubicin works in the body might change if a woman is pregnant.
• There are guidelines from the European Society for Medical Oncology (ESMO) for how to deal with cancer during pregnancy.
• They suggest that if chemotherapy is needed, it should not be given during the first three months of pregnancy. It can start during the second trimester.
• There should also be a three-week gap between the last chemotherapy dose and the expected delivery date, and chemotherapy should not be given after the 33rd week of pregnancy.

Epirubicin use during breastfeeding:

• Epirubicin might be found in breast milk because similar drugs are.
• Since there's a chance that this could harm the baby, the company making the drug suggests that mothers either stop breastfeeding or don't take the drug.
• The decision should consider how important the treatment is for the mother.

Epirubicin (Ellence) Dose adjustment in renal disease:

• The company that makes the drug says that if someone has really bad kidney problems (measured by a high serum creatinine level), they should take a lower dose of the drug.
• However, they don't specify exactly how much less.
• Another source says that even if the kidney function is a bit reduced (measured by CrCl), there's no need to change the dose.

Epirubicin (Ellence) Dose adjustment in liver disease:

If someone has liver issues, the manufacturer suggests adjusting the drug dosage based on specific tests:

• If bilirubin is between 1.2 and 3 mg/dL, or the AST level is 2 to 4 times higher than what's considered normal: Take half (50%) of the usual starting dose.
• If bilirubin is more than 3 mg/dL, or the AST level is more than 4 times the normal limit: Take only a quarter (25%) of the usual starting dose.
• If someone has very severe liver problems: They shouldn't use the drug since it hasn't been studied in such cases.

Side effects of Epirubicin (Ellence):

Percentages reported as part of combination chemotherapy regimens.

• Cardiovascular:
  • Decreased Left Ventricular Ejection Fraction
  • Cardiac Failure
  • Atrioventricular Block
  • Bradycardia
  • Bundle Branch Block
  • Cardiac Arrhythmia
  • Cardiomyopathy
  • ECG Abnormality
  • Myocarditis
  • Non-Specific T Wave On ECG
  • Sinus Tachycardia
  • ST Segment Changes On ECG
  • Tachyarrhythmia
  • Thromboembolism
  • Ventricular Premature Contractions
  • Ventricular Tachycardia
• Central Nervous System:
  • Lethargy
• Dermatologic:
  • Alopecia
  • Skin Rash
  • Skin Changes
• Endocrine & Metabolic:
  • Amenorrhea
  • Hot Flash
• Gastrointestinal:
  • Nausea And Vomiting
  • Mucositis
  • Diarrhea
  • Anorexia
  • Abdominal Pain
  • Esophagitis
  • Neutropenic Enterocolitis
  • Stomatitis
  • Toxic Megacolon
• Genitourinary:
  • Menopause
• Hematologic & Oncologic:
  • Neutropenia
  • Leukopenia
  • Anemia
  • Thrombocytopenia
  • Febrile Neutropenia
  • Acute Lymphocytic Leukemia
  • Acute Myelocytic Leukemia
  • Myelodysplastic Syndrome
• Hepatic:
  • Ascites
  • Hepatomegaly
  • Increased Serum Transaminases
• Hypersensitivity:
  • Hypersensitivity Reaction
• Infection:
  • Infection
• Local:
  • Injection Site Reaction
• Ophthalmic:
  • Conjunctivitis
• Respiratory:
  • Dyspnea
  • Pulmonary Edema
• Miscellaneous:
  • Fever

Contraindications to Epirubicin (Ellence):

People shouldn't take epirubicin if they:

• Are allergic to epirubicin, similar drugs (like other anthracyclines or anthracenediones), or any ingredient in the medicine.
• Have heart problems like heart failure, a recent heart attack, or serious irregular heart rhythms.
• Have already taken a full dose of similar drugs (like anthracyclines) in the past.

In Canada, there are more reasons people shouldn't take it:

• If they had a serious drop in blood cells because of other cancer treatments or radiation therapy.
• Have severe liver problems.

(Note: These extra reasons in Canada aren't listed in the U.S. guidelines.)

Canadian labeling: Additional contraindications (not in the US labeling):

• Significant myelosuppression induced by previous treatment with other chemotherapy agents or by radiotherapy
• Severe hepatic impairment.

Warnings and Precautions

Bone marrow suppression: [US Boxed Warning]:

• Epirubicin can seriously reduce the number of blood cells, including white blood cells, platelets, and red blood cells.
• This is the main reason doctors might stop increasing the drug dose.
• Before starting and during the treatment, regular blood tests are needed to check on these blood cells.
• If someone has low blood cell counts from another chemotherapy treatment, they should wait until their blood cell levels are back to normal before starting epirubicin.
• If they experience very low white blood cell counts or serious infections while on the drug, they might need extra care and support.

Cardiomyopathy: [US Boxed Warning]:

• Epirubicin can harm the heart. This can happen during treatment or even years after.
• There's a higher chance of heart issues the more of the drug you take.
• Taking more than a certain amount is risky and should be done very carefully.
• Heart problems might include irregular heartbeats or a weakened heart. The latter can lead to symptoms like rapid heart rate, difficulty breathing, and swelling.
• While the risks grow with the amount of the drug taken, heart issues can happen at any dose.
• Some people have a higher risk, like those with heart diseases, older people, kids, or if they've had certain treatments before.
• It's important to check heart health regularly when on this drug. Stop it if there are any heart issues.
• If taking other heart-related treatments, timing matters.

Guidelines about Heart Risk with Cancer Treatment:

• Higher doses of certain cancer treatments can increase heart risk.
• Some treatments can be riskier when combined or if a patient has other risk factors.
• Before starting such treatments, it's a good idea to check for risks like high blood pressure, diabetes, and obesity.
• Doctors should also look at the heart's health using tools like echocardiograms.
• It's important to manage and control these risks before starting the treatment.
• If someone is getting a high dose of these treatments, consider using drugs to protect the heart.
• If someone has symptoms of heart issues during treatment, they need to get checked right away, preferably with an echocardiogram or other heart tests.
• They might also need to see a heart specialist.

Extravasation: [US Boxed Warning]:

• Epirubicin is only for injection into the vein.
• If the drug leaks out of the vein, it can severely damage the surrounding tissue and even kill it.
• Don't inject it into the muscle or just under the skin.
• Injecting it repeatedly into the same vein or a small vein can cause that vein to harden.
• Before and during the infusion, ensure the needle or tube is correctly placed in the vein.
• Take care to avoid any leakage of the drug outside the vein.
• If leakage happens, immediately stop the infusion and start it in a different vein.

Gastrointestinal toxicity:

• Epirubicin can cause nausea and vomiting. Depending on the treatment plan, this can range from moderate to strong.
• To prevent these side effects, it's recommended to use medicines that stop nausea and vomiting.

Secondary malignancy: [US Boxed Warning]:

• Using drugs like epirubicin can increase the risk of getting a new kind of cancer called acute myeloid leukemia (AML).
• This risk is higher if used with other cancer drugs, if someone has had many rounds of chemotherapy, or if they're given higher doses of epirubicin.
• In people treated for breast cancer, the chance of getting AML or another condition, myelodysplastic syndrome (MDS), is low but increases over time. For example, after 3 years it's 0.27%, after 5 years it's 0.46%, and after 8 years it's 0.55%.
• The time between the treatment and getting this new type of cancer can be short, like 1 to 3 years.

Thromboembolic events:

• Using epirubicin can cause blood clot issues.
• This includes inflammation of the veins due to a blood clot and blood clots traveling to other parts of the body, like the lungs.

Tumor lysis syndrome:

• Epirubicin can cause a condition where cancer cells break down quickly, called tumor lysis syndrome (TLS).
• Even though it's rare in breast cancer patients, if there's a chance of getting TLS, doctors should keep an eye on certain blood markers.
• Drinking lots of fluids and taking certain medications can help prevent complications from TLS.

Hepatic impairment: [US Boxed Warning]:

• If someone has mild to moderate liver problems, they should take a reduced dose of epirubicin.
• If they have severe liver problems, they shouldn't use the drug at all.
• Before and during treatment, doctors should check how well the liver is working.
• Since the liver mainly processes epirubicin, if it's not working properly, there could be more of the drug in the body, leading to more side effects.

Renal impairment:

• If someone's blood test shows a high level of creatinine (over 5 mg/dL, which indicates kidney problems), they should take a reduced dose of epirubicin.
• Doctors should check kidney function before starting and throughout the treatment.
• The drug hasn't been studied in patients who are on dialysis.

Epirubicin: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Regular Checks:
  • Full blood count including details (CBC with differential).
  • Liver function.
  • Kidney function (serum creatinine).
  • Salt levels (electrolytes).
  • Heart checks (ECG and LVEF).
  • Always use the same method for LVEF checks, like echocardiogram or MUGA.
• During Treatment:
  • Watch the injection site for leakage (extravasation) or skin reactions.

Heart Monitoring (Based on ASCO [Armenian 2017])

• Before Treatment:
  • Thorough check-up including health history.
  • Look for heart disease risks like high blood pressure, diabetes, high cholesterol, obesity, and smoking.
  • Get an echocardiogram.
• If Heart Issues Appear During Treatment:
  • Get another echocardiogram.
  • If that's not possible, a cardiac MRI is preferred or use a MUGA scan.
  • Check heart-related blood markers.

How to administer Epirubicin (Ellence)?

Nausea and Vomiting:

• Epirubicin can cause moderate to severe nausea and vomiting.
• To prevent this, anti-nausea medications are advised (as per Hesketh 2017; Roila 2016).

How to Give Epirubicin:

• Via IV (in the vein) over 15 to 20 minutes or as a slow push.
• For reduced doses, the infusion time can be decreased proportionally.
• Don't give it in under 3 minutes.
• Inject into a flowing IV solution, like normal saline or D5W.
• Avoid using veins near joints or in areas with poor blood or lymph flow.

Important Note: Epirubicin can cause damage if it leaks out of the vein (vesicant). Always make sure the needle or tube is correctly placed.

What to Do If Epirubicin Leaks Out (Extravasation):

• If it leaks, stop the infusion and don't remove the needle.
• Try to gently pull out any leaked drug (without flushing the vein).
• Lift the affected arm or leg.
• Use either dexrazoxane or DMSO as an antidote.
• Use cold compresses for 1-2 days (but not with dexrazoxane).

Antidote Details:

• Dexrazoxane:
  • Given via IV, away from the leakage site.
  • Given over 1-2 hours for three days, but start within 6 hours of the leakage.
  • The second and third doses should be given around the same time as the first.
  • If the patient has kidney problems (CrCl <40 mL/minute), give half the dose.
• DMSO:
  • Apply it on the skin around the leak.
  • Start within 10 minutes of the leak and don't cover it.
  • Repeat every 8 hours for 7 days.

Note: Don't use DMSO with dexrazoxane together. They might reduce each other's effectiveness.

Mechanism of action of Epirubicin (Ellence).

• Epirubicin is a type of chemotherapy drug called an anthracycline.
• It blocks the building of DNA and RNA by fitting itself between the pairs of DNA bases.
• This interference with DNA causes it to break apart with the help of an enzyme called topoisomerase II, which ultimately kills cancer cells.
• Epirubicin also stops a process called DNA helicase, and it creates harmful molecules that further damage cancer cells.

Distribution:

• After being given, it spreads through the body and occupies a space of about 21 to 27 times the patient's weight (in liters).

Binding to Proteins:

• About 77% of the drug attaches itself to a protein called albumin in the blood.

Breaking Down (Metabolism):

• Epirubicin is majorly broken down in the liver, but also in other parts of the body including red blood cells.

How Long It Stays (Half-life):

• The drug has three phases of elimination from the body.
• On average, it takes about 33 hours for half of the drug to be removed.

How It Leaves the Body:

• About 34% to 35% of the drug leaves the body through feces (poop), and 20% to 27% through urine (pee).

International Brand Names of Epirubicin:

• Ellence
• Pharmorubicin PFS
• PMS-EpiRUBicin
• 4-Epeedo-50
• Adricin
• Ai Da Sheng
• Anthracin
• Binarin
• Bioepicyna
• Canrub
• Ciazil
• P.Mycin
• Eberubi
• Ecclepia
• Epi-Cell
• Epicin
• Epidoxo
• Epifil
• Epilem
• Epilim
• Epirol
• Epiruba
• Episindan
• Epivid
• Epizin
• Ericina
• Farmorrubicina RTU
• Farmorubicin
• Farmorubicin CSU
• Farmorubicin PFS
• Farmorubicin RD
• Farmorubicina
• Farmorubicina CS
• Farmorubicina R.D.
• Farmorubicine
• Favicin
• Grubin
• Neoquabin
• Panbicin
• Pharmarubicin RD
• Pharmorubicin
• Pharmorubicin CS
• Pharmorubicin PDF
• Pharmorubicin PFS
• Pharmorubicin RD
• Riboepi
• Rubisandin

Epirubicin Brand Names in Pakistan: