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:
- IV: 40 mg/m² once every 14 days;
- Use till disease progression.
Use in Children:
Not indicated.
Pregnancy Risk Factor D
- In animal reproduction studies, there were unfavorable events.
Use while breastfeeding
- For advanced HIV-associated Kaposi Sarcoma, Daunorubicin (liposomal), is indicated.
- If a formula is not available in the US and there is a low risk of infant death from diarrhea or lung infections, then a formula can be found. However, if a formula is not available, it is safe to breastfeed.
Dose in Kidney Disease:
- Serum creatinine >3 mg/dL: Administer half of the normal dose.
Dose in Liver disease:
- Bilirubin 1.2 to 3 mg/dL: Administer 75% of usual dose.
- Bilirubin >3 mg/dL: Administer 50% of 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):
- Allergy to daunorubicin (liposomal), or any component of the formulation
- It is difficult to document allergenic cross-reactivity of drugs within this class.
- Cross-sensitivity is possible due to similarities in chemical compositions and pharmacologic actions.
- However, cross-sensitivity cannot always be ruled out.
Warnings and precautions
-
Suppression of bone marrow: [US Boxed Warning]
- This may cause bone marrow suppression and neutropenia, which can be very serious.
- Monitor blood counts. You should monitor your body for any infections, even opportunistic ones.
-
Extravasation
- Avoid extravasation. Even though it is not associated with daunorubicin, liposomal, daunorubicin conventional can cause tissue necrosis in local tissues if extravasated.
-
Infusion reactions: [US Boxed Warning]
- Infusion-related effects such as back pain, flushing, or tightness are usually experienced within the first five minutes of infusion. This effect is typically gone if the infusion rate is decreased.
- Infusion reactions should be checked. If a reaction occurs, stop the infusion and restart at a lower rate.
-
Myocardial toxicity: [US Boxed Warning]
- Patients who have had treatment with anthracyclines or thoracic radiation in the past, or who have a pre-existing heart disease, should be monitored for signs of cardiac dysfunction.
- Cardiomyopathy is often associated with a decrease in left ventricular Ejection Fraction (LVEF).
- While the risk of permanent cardiotoxicity increases with increasing doses, it is possible to develop permanent heart disease with any dosage level of anthracycline therapy.
- Patients who have had prior anthracycline treatment (DOXOrubicin>300 mg/m2 or equivalent), pre-existing heart disease, high bloodpressure, concurrent administration of antineoplastic agents or advanced age, are at higher risk.
- Before treatment, assess LVEF regularly throughout treatment.
-
Hepatic impairment: [US-Boxed Warning]
- Patients with hepatic impairment should be given a lower dose.
-
Renal impairment
- Patients with kidney damage should be cautious; you may need to lower the dose.
Liposomal daunorubicin (United States: Not available): Drug Interaction
|
Cardiac Glycosides |
May diminish the cardiotoxic effect of Anthracyclines. Anthracyclines may decrease the serum concentration of Cardiac Glycosides. The effects of liposomal formulations may be unique from those of the free drug, as liposomal formulation have unique drug disposition and toxicity profiles, and liposomes themselves may alter digoxin absorption/distribution. |
|
Chloramphenicol (Ophthalmic) |
May enhance the adverse/toxic effect of Myelosuppressive Agents. |
|
CloZAPine |
|
|
Coccidioides immitis Skin Test |
Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. |
|
Cyclophosphamide |
May enhance the cardiotoxic effect of Anthracyclines. |
|
Denosumab |
May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. |
|
Erdafitinib |
May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. |
|
Lumacaftor |
May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. |
|
Mesalamine |
May enhance the myelosuppressive effect of Myelosuppressive Agents. |
|
Ocrelizumab |
May enhance the immunosuppressive effect of Immunosuppressants. |
|
P-glycoprotein/ABCB1 Inducers |
May decrease the serum concentration of Pglycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). |
|
P-glycoprotein/ABCB1 Inhibitors |
May increase the serum concentration of Pglycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of pglycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). |
|
Pidotimod |
Immunosuppressants may diminish the therapeutic effect of Pidotimod. |
|
Promazine |
May enhance the myelosuppressive effect of Myelosuppressive Agents. |
|
Ranolazine |
May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. |
|
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). |
|
Tertomotide |
Immunosuppressants may diminish the therapeutic effect of Tertomotide. |
|
Risk Factor D (Consider therapy modification) |
|
|
Ado-Trastuzumab Emtansine |
May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with ado-trastuzumab emtansine should avoid anthracycline-based therapy for up to 7 months after stopping ado-trastuzumab emtansine. Monitor closely for cardiac dysfunction in patients receiving this combination. |
|
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. |
|
Deferiprone |
|
|
Echinacea |
May diminish the therapeutic effect of Immunosuppressants. |
|
Fam-Trastuzumab Deruxtecan |
May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with fam-trastuzumab deruxtecan should avoid anthracycline-based therapy for up to 7 months after stopping fam-trastuzumab deruxtecan. Monitor closely for cardiac dysfunction in patients receiving this combination. |
|
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. |
|
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. |
|
Taxane Derivatives |
May enhance the adverse/toxic effect of Anthracyclines. Taxane Derivatives may increase the serum concentration of Anthracyclines. Taxane Derivatives may also increase the formation of toxic anthracycline metabolites in heart tissue. |
|
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. |
|
Trastuzumab |
May enhance the cardiotoxic effect of Anthracyclines. Management: When possible, patients treated with trastuzumab should avoid anthracycline-based therapy for up to 7 months after stopping trastuzumab. Monitor closely for cardiac dysfunction in patients receiving anthracyclines with trastuzumab. |
|
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). |
|
Bevacizumab |
May enhance the cardiotoxic effect of Anthracyclines. |
|
Cladribine |
May enhance the immunosuppressive effect of Immunosuppressants. |
|
Cladribine |
May enhance the myelosuppressive effect of Myelosuppressive Agents. |
|
Dipyrone |
May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased |
|
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. |
|
Pimecrolimus |
May enhance the adverse/toxic effect of Immunosuppressants. |
|
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:
- CBC with differential (prior each dose)
- Tests of liver function
- Tests of kidney function
- Before starting therapy, evaluate cardiac function (baseline leftventricular ejection fraction [LVEF]).
- Repeat LVEF at cumulative doses totalling 320 mg/m2 and every 160 mg/m thereafter;
- Patients with pre-existing heart disease, history prior to chest irradiation or history prior anthracycline therapy should have baseline LVEF, and then every 160 mg/m2.
- Signs and symptoms of disease progression or infection;
- Infusion reactions should be closely monitored.
How to administer Liposomal Daunorubicin (DaunoXome)?
IV: Infuse over one hour; do not mix with other drugs. Do NOT GIVE with an in-line filter. Avoid extravasation.
Mechanism of action of Liposomal Daunorubicin (DaunoXome):
- Liposomes are a lipomal formulation for daunorubicin.
- They have been shown to penetrate solid tumors more effectively, possibly because they are smaller and last longer.
- Daunorubicin can be released from tissues once it is inhaled.
- Daunorubicin inhibits DNA synthesis and intercalation between DNA base pair.
- It also causes steric obstruction, intercalates at points where the double helix is being uncoilled locally.
- Although the exact mechanism is not clear, it appears that intercalation and topoisomerase II inhibition result in DNA synthesis and DNA fragmentation.
Metabolism:
- Daunorubicinol (major active metabolite) is detected at low levels in plasma
Half-life elimination:
- Distribution: 4.4 hours
Excretion:
- Primarily feces;
- some urine
International Brand Names of Liposomal Daunorubicin:
- DaunoXome
- Daunoxome
Liposomal Daunorubicin Brand Names in Pakistan:
No Brands Available in Pakistan.
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