Liposomal daunorubicin, often known under the trade name "DaunoXome", is a formulation of the chemotherapy drug daunorubicin encapsulated in liposomes. Liposomes are small, lipid-based vesicles that can encapsulate and deliver drugs to specific areas of the body. By delivering the drug in this way, the intent is to reduce side effects and improve the therapeutic index of the drug.

Liposomal Daunorubicin (DaunoXome) is a liposomal formulation of daunorubicin (entrapped into lipososomes). This formulation is thought to increase blastic cell exposure and prevent the active drug from getting exposed to enzymatic degradation by intracellular proteins.

Liposomal daunorubicin Uses:

• Kaposi sarcoma:
  • First-line treatment of advanced HIV-associated Kaposi sarcoma
  • Limitation of use: Daunorubicin (liposomal) is not suggested in HIV-related Kaposi sarcoma which is less than advanced.

Liposomal Daunorubicin (DaunoXome) Dose in Adults:

Note: DaunoXome has been suspended in the US for more than 1 year.

Note: DAUNOrubicin (liposomal) is different from the standard DAUNOrubicin formulation; do NOT replace (indications and doses are different).

Liposomal Daunorubicin (DaunoXome) Dose in the treatment of Kaposi sarcoma:

For treating Kaposi's sarcoma with Liposomal Daunorubicin (like DaunoXome):

• The medicine is given through a vein (IV).
• The dose is 40 mg for every square meter of the person's body surface area.
• It's given once every 2 weeks.
• The treatment goes on until the disease gets worse or shows signs of advancing.

Use in Children:

Not indicated.

Pregnancy Risk Factor D

• In studies with animals, some negative effects were seen when they were trying to have babies (reproduce) after being given the medicine.

Use while breastfeeding

• Daunorubicin (liposomal) is used to treat a type of cancer called Kaposi sarcoma in people with advanced HIV.
• In the US, where baby formula is easy to get, safe, and affordable, women with HIV are advised not to breastfeed.
• This is to prevent passing HIV to the baby.
• This recommendation comes from the US Health Department guidelines from 2018.

Dose in Kidney Disease:

• If the blood test shows a serum creatinine level higher than 3 mg/dL, then only give half of the usual dose of the medicine.

Dose in Liver disease:

• If the blood test shows bilirubin levels between 1.2 and 3 mg/dL, give three-quarters (or 75%) of the usual medicine dose.
• If the bilirubin level is more than 3 mg/dL, give only half (or 50%) of the usual dose.

Side effects of Liposomal Daunorubicin (DaunoXome):

• Cardiovascular:
  • Edema
  • Chest Pain
  • Angina Pectoris
  • Atrial Fibrillation
  • Cardiac Arrest
  • Cardiac Tamponade
  • Hypertension
  • Myocardial Infarction
  • Palpitations
  • Pericardial Effusion
  • Pulmonary Hypertension
  • Sinus Tachycardia
  • Supraventricular Tachycardia
  • Syncope
  • Tachycardia
  • Ventricular Premature Contractions
  • Decreased Left Ventricular Ejection Fraction
  • Cardiomyopathy
• Central Nervous System:
  • Fatigue
  • Headache
  • Rigors
  • Neuropathy
  • Depression
  • Malaise
  • Dizziness
  • Insomnia
  • Abnormality In Thinking
  • Amnesia
  • Anxiety
  • Ataxia
  • Confusion
  • Drowsiness
  • Emotional Lability
  • Hallucination
  • Hypertonia
  • Meningitis
  • Seizure
• Dermatologic:
  • Diaphoresis
  • Alopecia
  • Pruritus
  • Folliculitis
  • Seborrhea
  • Xeroderma
• Endocrine & Metabolic:
  • Dehydration
  • Hot Flash
  • Increased Thirst
• Gastrointestinal:
  • Nausea
  • Diarrhea
  • Abdominal Pain
  • Anorexia
  • Vomiting
  • Stomatitis
  • Constipation
  • Tenesmus
  • Dental Caries
  • Dysgeusia
  • Dysphagia
  • Gastritis
  • Gastrointestinal Hemorrhage
  • Gingival Hemorrhage
  • Hemorrhoids
  • Hiccups
  • Increased Appetite
  • Melena
  • Xerostomia
• Genitourinary:
  • Dysuria
  • Nocturia
• Hematologic & Oncologic:
  • Neutropenia
  • Lymphadenopathy
  • Splenomegaly
  • Bone Marrow Depression
  • Severe Granulocytopenia
• Hepatic:
  • Hepatomegaly
• Hypersensitivity:
  • Hypersensitivity Reaction
• Infection:
  • Opportunistic Infection
• Local:
  • Inflammation At Injection Site
• Neuromuscular & Skeletal:
  • Back Pain
  • Arthralgia
  • Myalgia
  • Abnormal Gait
  • Hyperkinesia
  • Tremor
• Ophthalmic:
  • Visual Disturbance
  • Conjunctivitis
  • Eye Pain
• Otic:
  • Deafness
  • Otalgia
  • Tinnitus
• Renal:
  • Polyuria
• Respiratory:
  • Cough
  • Dyspnea
  • Rhinitis
  • Sinusitis
  • Flu-Like Symptoms
  • Hemoptysis
  • Increased Bronchial Secretions
  • Pulmonary Infiltrates
• Miscellaneous:
  • Fever
  • Infusion-related reaction Includes
    • Back pain
    • Flushing
    • Chest tightness

Contraindications to Liposomal Daunorubicin (DaunoXome):

• If someone is allergic to Daunorubicin (liposomal) or anything in its mixture, they shouldn't take it.
• Even though we don't have a lot of info on whether people allergic to this drug might be allergic to similar drugs, it's possible.
• Because these drugs can be similar in their makeup or how they work, being allergic to one might mean you could be allergic to others.

Warnings and precautions

Suppression of bone marrow: [US Boxed Warning]

• This medicine can seriously affect the bone marrow, which is where our body makes blood cells.
• The biggest concern is a drop in a type of white blood cell called neutrophils.
• This can lead to severe infections, including rare ones that take advantage of a weakened immune system.
• Always keep an eye on blood levels and watch out for signs of infection.

Extravasation

• Make sure the medicine doesn't leak out of the vein when giving it (this is called extravasation).
• Even though this issue hasn't been seen with Daunorubicin (liposomal), the regular form of Daunorubicin can damage local tissues if it leaks out.
• Always be careful when giving the injection and monitor the site closely.

Infusion reactions: [US Boxed Warning]

• When giving this medicine through an IV, some people might have reactions like back pain, redness in the face, or feeling tightness in the chest.
• These reactions usually happen within the first 5 minutes.
• If this occurs, stop the infusion right away.
• Once the reaction calms down, you can start the infusion again but at a slower rate.
• Always keep a close eye on the person getting the medicine and be ready to adjust if needed.

Myocardial toxicity: [US Boxed Warning]

• This medicine could potentially harm the heart and lead to heart problems.
• It's important to regularly check the heart's function, especially in people who have had similar treatments before, received chest radiation, or have heart issues.
• Heart problems could result in a weakened pumping of the heart (left ventricular ejection fraction or LVEF).
• Even though the risk goes up with the total amount of medicine given, heart issues can happen at any dose.
• People who've had a lot of a similar medicine (DOXOrubicin >300 mg/m or similar), those with heart conditions, high blood pressure, those taking other cancer drugs, and older people are at higher risk.
• Doctors should check the heart's function before and during treatment, especially at certain cumulative doses or for those at higher risk.

Hepatic impairment: [US-Boxed Warning]

• If someone has liver problems, they should get a smaller dose of this medicine.

Renal impairment

• If someone has kidney problems, be careful when using this medicine.
• They might need a smaller dose.

Liposomal Daunorubicin: Drug Interaction

Monitoring parameters:

• Blood Tests:
  • Complete Blood Count (CBC) to check different types of blood cells.
  • Platelets, which help with clotting.

Liver and Kidney Checks:

• Tests to see how the liver and kidneys are working.

Heart Health Monitoring:

• Measure the heart's pumping ability (LVEF) before starting the medicine.
• Check LVEF again after getting a total of 320 mg/m^2 of the medicine and every 160 mg/m^2 after that.
• People with a history of heart problems, chest radiation, or certain treatments should have extra LVEF checks every 160 mg/m^2.

Other Monitoring:

• Watch for signs of infections or if the disease gets worse.
• Be alert for reactions during the medicine infusion.

How to administer Liposomal Daunorubicin (DaunoXome)?

• Time: Give it over 1 hour.
• Mixing: Don't mix it with other medicines.
• Equipment: Don't use an in-line filter when giving it.
• Caution: Make sure it doesn't leak out of the vein (avoid extravasation).

Mechanism of action of Liposomal Daunorubicin (DaunoXome):

Liposomal daunorubicin is a special type of daunorubicin that's wrapped in tiny fat bubbles called liposomes. These liposomes can get into solid tumors better because they're small and stay in the bloodstream for longer.

• Release in Tissues: Once in the body's tissues, the daunorubicin gets released slowly over time.
• How Daunorubicin Acts:
  • DNA and RNA Inhibition: Daunorubicin stops the making of DNA and RNA, which are important for cell growth.
  • DNA Intercalation: It sneaks in between the building blocks of DNA (base pairs) and causes a sort of blockage.
  • Blocking DNA Repair: Daunorubicin also messes with DNA repair, causing damage.
• Result: The exact process isn't entirely understood, but this combination of sticking to DNA and stopping its repair ends up blocking the creation of DNA and RNA, and it breaks up DNA too.

Distribution:

• Volume (V): The medicine spreads out in the body, taking up a space of around 5 to 8 liters.

Metabolism:

• When the body breaks down daunorubicin, it creates a major byproduct called "Daunorubicinol". This byproduct is active but only found in small amounts in the blood.

Half-life:

• Distribution Phase: This is about 4.4 hours. Half-life means the time it takes for half of the medicine to leave the system or be broken down.

Getting Rid of the Medicine:

• Mainly Through Stool: Most of the medicine goes out of the body through feces (poop).
• A Bit Through Urine: Some of it is also removed in urine (pee).

International Brand Names of Liposomal Daunorubicin:

• DaunoXome
• Daunoxome

Liposomal Daunorubicin Brand Names in Pakistan:

Update soon.