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Doxil (Pegylated Liposomal Doxorubicin) - Uses, Dose, Side effects

Pegylated liposomal doxorubicin, often abbreviated as PLD, is a medication used in cancer treatment. It is a specialized formulation of the chemotherapy drug doxorubicin, designed to improve its therapeutic properties and reduce some of its side effects.

Doxil (Pegylated Liposomal Doxorubicin) is anthracycline chemotherapeutic antineoplastic drug that is used to treat multiple myeloma, breast, and ovarian cancer.

Indications of Pegylated liposomal doxorubicin (Doxil):

AIDS-related Kaposi sarcoma:
- It is indicated for the treatment of AIDS-related Kaposi sarcoma (after the failure of or intolerance to prior systemic therapy).
Multiple myeloma:
- It is used for the treatment of multiple myeloma (in combination with bortezomib) in patients who are bortezomib-naïve and have received at least 1 prior therapy.
Advanced Ovarian cancer:
- Treatment of progressive or recurrent ovarian cancer (after platinum-based treatment) can be done by pegylated doxorubicin.
Off Label Use of Pegylated liposomal doxorubicin in Adults:
- Breast cancer, metastatic
- Hodgkin lymphoma (salvage treatment)
- Cutaneous T-cell lymphomas (mycosis fungoides and Sézary syndrome)
- Advanced Soft tissue sarcomas
- Advanced or recurrent Uterine sarcoma

Pegylated liposomal doxorubicin dose in adults:

Liposomal formulations of doxorubicin should NOT be substituted for conventional doxorubicin hydrochloride on an mg-per-mg basis.

Doxil Treatment dose of AIDS-related Kaposi sarcoma:

For treating AIDS-related Kaposi sarcoma, a medicine called "pegylated liposomal doxorubicin" is given through an IV (a drip into the vein).
The amount given is 20 mg for every square meter of the patient's body surface area.
This treatment is given once every 3 weeks.
It continues until the disease gets worse or the side effects become too severe.

Doxil Treatment dose of Multiple myeloma:

For treating Multiple myeloma, the medicine "pegylated liposomal doxorubicin" is given through an IV (a drip into the vein).
The dose is 30 mg for every square meter of the patient's body surface area.
This is given on the 4th day, once every 3 weeks, and it's combined with another medicine called bortezomib.
The treatment is repeated up to 8 times or until the disease gets worse or the side effects become too much to handle.

Doxil Treatment dose of newly diagnosed multiple myeloma (off-label dosing):

For new cases of Multiple myeloma, "pegylated liposomal doxorubicin" is used as a treatment.
It's given through an IV (directly into the bloodstream).
The dose is 40 mg for every square meter of the patient's body size.
This is administered on the first day and then repeated every 4 weeks.
It's combined with two other medicines: vincristine and dexamethasone.
This treatment is done for at least 4 cycles.

Doxil Treatment dose of advanced Ovarian cancer:

For treating advanced Ovarian cancer, the medicine "pegylated liposomal doxorubicin" is given through an IV (a drip into the vein).
The amount given is 50 mg for every square meter of the patient's body surface area.
This treatment is given once every 4 weeks.
It continues until the cancer gets worse or the side effects become too severe.

Doxil Treatment dose of advanced, recurrent Ovarian cancer, (off- label dosing):

Alone:

The medicine "pegylated liposomal doxorubicin" is given through an IV (drip into the vein).
The dose is 40 mg for every square meter of the patient's body size.
This is given once every 4 weeks.
Treatment continues until the cancer worsens or the side effects are too harsh.
(Based on studies by Ferrandina 2008 & Rose 2001).

With carboplatin:

The dose is 30 mg for every square meter of the patient's body size, given once every 4 weeks.
This combination treatment lasts for at least 6 cycles.
(Based on Pujade-Lauraine 2010).

With bevacizumab:

The dose is 40 mg for every square meter of the patient's body size, given once every 4 weeks.
This is continued until the cancer progresses or the side effects become too severe.
(From the study by Pujade-Lauraine 2014).

Doxil Treatment dose of metastatic Breast cancer, (off-label):

The medicine "pegylated liposomal doxorubicin" is given through an IV (directly into the bloodstream).
The dose is 50 mg for every square meter of the patient's body size.
This treatment is given once every 4 weeks.
The recommendation comes from a study by Keller in 2004.

Doxil Treatment dose of Cutaneous T-cell lymphomas (off-label):

According to Dummer 2012:
- The medicine "pegylated liposomal doxorubicin" is given through an IV (drip into the vein).
- The dose is 20 mg for every square meter of the patient's body size.
- This treatment is given on days 1 and 15, repeated every 4 weeks, for a total of 6 cycles.
Based on Wollina 2003:
- The same medicine is given with a dose of 20 mg for every square meter of the patient's body size, but only once every 4 weeks.

Doxil Treatment dose of Hodgkin lymphoma, salvage (off-label):

Posttransplant patients:
- They receive 10 mg for every square meter of their body size.
- This treatment is given on days 1 and 8, and it's repeated every 3 weeks.
- It can be done for 2 to 6 cycles.
Transplant-naive patients:
- They receive a slightly higher dose of 15 mg for every square meter of their body size.
- The treatment schedule is the same, with dosages on days 1 and 8 every 3 weeks for 2 to 6 cycles.
- This information is based on a study by Bartlett in 2007.

Doxil Treatment dose of advanced Soft tissue sarcoma, (off-label):

The medicine "pegylated liposomal doxorubicin" is given through an IV (drip into the vein).
The dose is 50 mg for every square meter of the patient's body size.
This treatment is given once every 4 weeks, and it's typically done for a total of 6 cycles.
This information comes from a study by Judson in 2001.

Doxil Treatment dose of advanced or recurrent Uterine sarcoma, (off-label):

The medicine "pegylated liposomal doxorubicin" is given through an IV (directly into the bloodstream).
The amount is 50 mg for every square meter of the patient's body size.
This treatment is provided once every 4 weeks and continues until the disease worsens or the side effects are too severe.
The recommendation is based on a study by Sutton in 2005.

Pegylated liposomal doxorubicin Use in Children:

Not indicated

Doxil pregnancy Risk Category: D

Doxorubicin (liposomal) might harm an unborn baby if given during pregnancy based on animal studies.
Both men and women who could have children should use reliable birth control during the treatment and for 6 months after.
This medicine can affect fertility, making it harder to have children.
In men, it might damage sperm and in some cases, this could be permanent, though some men have seen their sperm count return to normal after a few years.
Women might experience issues like missed periods or early menopause.
It's not clear if this medicine gets into breast milk, but due to potential risks, breastfeeding mothers should not take it.

Use while breastfeeding

It is not known if breast milk contains Doxorubicin liposomal Secretion.
Due to the possibility of side effects, it is important that you stop breast-feeding during treatment.

Doxil Dose adjustment in renal disease:

The manufacturer hasn't given any guidance on changing the dose for people with kidney problems (it hasn't been researched).

Doxil Dose adjustment in liver disease:

US Labeling:

The manufacturer hasn't provided dosage adjustments.
However, doxorubicin mainly exits the body through the liver, so it's advised to give lower doses to patients with a serum bilirubin level of 1.2 mg/dL or higher.

Canadian Labeling:

For AIDS-related Kaposi sarcoma:
- If bilirubin is between 1.2 and 3 mg/dL: Give half the usual dose.
- If bilirubin is more than 3 mg/dL: Give a quarter of the usual dose.
For Breast and Ovarian cancer:
- If bilirubin is between 1.2 and 3 mg/dL: Start with 75% of the usual dose. If that's well-tolerated and bilirubin/hepatic enzymes don't change, the full dose can be given from the second cycle onward.
- If bilirubin is more than 3 mg/dL: Start with half the usual dose. If well-tolerated, the dose can be increased to 75% for the second cycle. If the second cycle is also well-tolerated, the full dose can be given from then on.

Common Side Effects of Pegylated liposomal doxorubicin (Doxil):

Cardiovascular:
- Cardiomyopathy
- Cardiotoxicity
- Chest Tightness
- Flushing
- Hypotension
Central Nervous System:
- Fatigue
- Headache
Dermatologic:
- Palmar-Plantar Erythrodysesthesia
- Skin Rash
- Alopecia
- Facial Swelling
Gastrointestinal:
- Nausea
- Stomatitis
- Vomiting
- Constipation
- Diarrhea
- Anorexia
- Mucous Membrane Disease
- Dyspepsia
Hematologic & Oncologic:
- Thrombocytopenia
- Neutropenia
- Leukopenia
- Anemia
Neuromuscular & Skeletal:
- Weakness
- Back Pain
Respiratory:
- Pharyngitis
- Dyspnea
Miscellaneous:
- Fever
- Infusion Related Reaction

Rare Side Effects Of Pegylated Liposomal Doxorubicin (Doxil):

Cardiovascular:
- Cardiac Arrest
- Chest Pain
- Deep Thrombophlebitis
- Tachycardia
- Vasodilation
Central Nervous System:
- Depression
- Dizziness
- Drowsiness
- Chills
Dermatologic:
- Acne Vulgaris
- Ecchymoses
- Exfoliative Dermatitis
- Fungal Dermatitis
- Furunculosis
- Herpes Simplex Dermatitis
- Pruritus
- Skin Discoloration
- Vesiculobullous Dermatitis
- Xeroderma
- Maculopapular Rash
Endocrine & Metabolic:
- Hypercalcemia
- Hypokalemia
- Hyponatremia
- Weight Loss
- Dehydration
- Hyperglycemia
Gastrointestinal:
- Dysphagia
- Esophagitis
- Intestinal Obstruction
- Oral Candidiasis
- Oral Mucosa Ulcer
- Dysgeusia
- Abdomen Enlarged
- Glossitis
- Cachexia
Genitourinary:
- Hematuria
- Hemorrhagic Cystitis
- Urinary Tract Infection
- Vulvovaginal Candidiasis
Hematologic & Oncologic:
- Rectal Hemorrhage
- Hemolysis
- Prolonged Prothrombin Time
- Bone Marrow Depression
- Progression Of Cancer
Hepatic:
- Hyperbilirubinemia
- Increased Serum Alkaline Phosphatase
- Increased Serum ALT
Hypersensitivity:
- Hypersensitivity Reaction
Infection:
- Infection
- Herpes Zoster
- Paresthesia
- Myalgia
- Neuropathy
- Toxoplasmosis
Ophthalmic:
- Dry Eye Syndrome
- Conjunctivitis
- Retinitis Optic Neuritis
Respiratory:
- Epistaxis
- Pneumonia
- Rhinitis
- Sinusitis
- Increased Cough
- Cough

Contraindications to Pegylated liposomal doxorubicin (Doxil):

People who have had serious allergic reactions (like anaphylaxis) to doxorubicin liposomal, regular doxorubicin, or any ingredient in the medicine shouldn't take it.

Canadian Labeling:

There are extra reasons listed in Canada for why someone shouldn't take this medicine that aren't mentioned in the US instructions.

Warnings and precautions

Suppression of bone marrow

Taking this medicine can lead to lower levels of certain blood cells, like neutrophils, red blood cells, and platelets.
It's important to regularly check blood counts.
Depending on the results, it might be necessary to delay treatment, adjust the dose, or even stop the medicine.
The risk of these blood problems can be higher and more severe if this drug is taken with other chemotherapy medicines.

Infusion reactions: [US Boxed Warning]

When receiving this medicine through an IV, some patients may experience immediate reactions like flushing, breathing difficulties, facial swelling, headaches, chills, chest tightness, or low blood pressure.
These reactions can be serious, life-threatening, or even fatal.
Other symptoms may include chest pain, itching, skin rash, bluish skin, fainting, fast heartbeat, wheezing, or breathing difficulties.
Most reactions happen during the first infusion.
In some cases, the dose might need to be stopped temporarily.
It's crucial to have the right medication and equipment ready to manage these reactions during the infusion.
To lower the risk, the infusion usually starts slowly (1 mg/minute) and gradually increases to complete over 60 minutes.
If an infusion reaction occurs, the infusion is paused until the reaction is resolved, and then it continues at a slower rate.
If the reaction is severe or life-threatening, the treatment is stopped.

Myocardial toxicity: [US Boxed Warning]

Doxorubicin liposomal can harm the heart, especially as the total dose taken gets close to 550 mg/m^2.
In a study with 250 cancer patients, there was an 11% risk of heart issues when the total dose was between 450 to 550 mg/m^2.
If a patient has used similar drugs before, those doses should be counted toward the total.
People who've had chest radiation might be at a higher risk even at lower doses.
Heart damage might show up as heart failure.
It's defined by certain drops in how well the heart pumps blood.
Some people might feel heart failure symptoms without clear test results.
The heart risk generally grows with the total dose, but the exact risk with doxorubicin liposomal isn't fully known.
This heart damage can even show up after stopping the drug.
Before and during treatment, doctors should check the heart's pumping function and continue to check afterwards for any delayed heart issues.
Only use this drug in patients with past heart problems if the benefits are greater than the heart risks.

Palmar-plantar Erythrodysesthesia (handfoot syndrome)

Patients taking doxorubicin liposomal might get hand-foot syndrome.
This typically appears after 2 to 3 rounds of treatment but can happen earlier.
It affects the palms of the hands and soles of the feet.
Depending on the severity, the dose might need to be adjusted, or in extreme cases, the treatment might need to be stopped altogether.

Secondary malignancy

Some patients who've been on doxorubicin liposomal for a long time (more than a year) have developed a second type of cancer, mainly in the mouth (squamous cell carcinoma).
This new cancer has been found both during the treatment and up to 6 years after stopping it.
Patients taking this drug should be checked for mouth sores or discomfort.
The way this medicine interacts with tissues, being enclosed in tiny "liposomes", might be a factor in causing these secondary mouth cancers with long-term use.

Hepatic impairment

The effects of doxorubicin liposomal on patients with liver problems haven't been fully studied.
Since the medicine mainly exits the body through the liver, doses should be lowered for patients with a blood bilirubin level of 1.2 mg/dL or higher.

Pegylated liposomal doxorubicin: Drug Interaction

Risk Factor C (Monitor therapy)
Ajmaline	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Aprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Bosentan	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
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.
CloBAZam	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Clofazimine	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
CloZAPine	Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased.
Coccidioides immitis Skin Test	Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test.
Cyclophosphamide	May enhance the cardiotoxic effect of Anthracyclines.
CYP2D6 Inhibitors (Moderate)	May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors).
CYP3A4 Inducers (Moderate)	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
CYP3A4 Inhibitors (Moderate)	May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors).
Deferasirox	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Denosumab	May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased.
Duvelisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Erdafitinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Erdafitinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fosaprepitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Fosnetupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Imatinib	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Ivosidenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Larotrectinib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Lumefantrine	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Mesalamine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
Netupitant	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Ocrelizumab	May enhance the immunosuppressive effect of Immunosuppressants.
Palbociclib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Panobinostat	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Peginterferon Alfa-2b	May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Pegloticase	May diminish the therapeutic effect of PEGylated Drug Products.
Pegvaliase	PEGylated Drug Products may enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased.
Pidotimod	Immunosuppressants may diminish the therapeutic effect of Pidotimod.
Promazine	May enhance the myelosuppressive effect of Myelosuppressive Agents.
QuiNINE	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
Sarilumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Siltuximab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Simeprevir	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Siponimod	Immunosuppressants may enhance the immunosuppressive effect of Siponimod.
Stavudine	DOXOrubicin (Liposomal) may diminish the therapeutic effect of Stavudine.
Tertomotide	Immunosuppressants may diminish the therapeutic effect of Tertomotide.
Tocilizumab	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers).
Vinflunine	DOXOrubicin (Liposomal) may enhance the adverse/toxic effect of Vinflunine. Specifically, the risk for hematologic toxicities may be increased. DOXOrubicin (Liposomal) may increase the serum concentration of Vinflunine. Vinflunine may decrease the serum concentration of DOXOrubicin (Liposomal).
Risk Factor D (Consider therapy modification)
Abiraterone Acetate	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity.
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.
Asunaprevir	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors).
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.
CYP2D6 Inhibitors (Strong)	May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors).
CYP3A4 Inducers (Strong)	May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
CYP3A4 Inhibitors (Strong	May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors).
Dabrafenib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects).
Dacomitinib	May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index.
Deferiprone	Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely.
Echinacea	May diminish the therapeutic effect of Immunosuppressants.
Enzalutamide	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring.
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.
Lorlatinib	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences.
MiFEPRIStone	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus.
Mitotane	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane.
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.
St John's Wort	May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling.
Stiripentol	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring.
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.
Zidovudine	DOXOrubicin (Liposomal) may enhance the adverse/toxic effect of Zidovudine. DOXOrubicin (Liposomal) may diminish the therapeutic effect of Zidovudine.
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.
Conivaptan	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Dipyrone	May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased
Fusidic Acid (Systemic)	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
Idelalisib	May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors).
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.
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.

Monitoring parameters:

Blood Tests:

Complete Blood Count (CBC) to check different types of blood cells.
Platelet count to measure blood clotting cells.
Liver function tests:
- ALT/AST: Enzymes to check liver health.
- Bilirubin: A substance the liver produces.
- Alkaline phosphatase: Another enzyme related to liver function.

What to Watch For:

Check the site where the medicine is infused for any issues.
Be on the lookout for immediate reactions during the infusion.
Watch for hand-foot syndrome, which affects the palms and soles.
Monitor for mouth issues like sores, discomfort, or signs of a secondary mouth cancer.

Heart Checks:

Assess the heart's pumping ability (LVEF):
- At the start (baseline) and then at regular intervals.
Use tools like echocardiography or MUGA scan for these checks.

How to administer Doxil (Pegylated liposomal doxorubicin)?

Monitor closely for any infusion reactions.
Do not administer as an IV push (rapid injection).
If it contacts the skin or mucous membranes, wash it off immediately with soap and water.

IVPB (Intravenous Piggyback) Administration:

Administer over 60 minutes.
For the first dose, begin with a slow rate of 1 mg/minute to reduce the risk of infusion reactions.
If there are no infusion-related reactions, increase the infusion rate to complete it within 1 hour.
Do not give it undiluted.
Do not use in-line filters.
Do not mix with other medications.
Watch for any red streaks along the vein or facial flushing, which might mean the infusion rate is too fast.

Multiple Myeloma Treatment:

For multiple myeloma, give doxorubicin liposomal after bortezomib on day 4 of each treatment cycle.

Irritation Risk:

This medicine can be irritating to tissues (Perez Fidalgo 2012).
Keep an eye on the infusion site.
Be careful to avoid it leaking into the surrounding area.

Extravasation (Leakage) Management:

If there's extravasation (leakage), infiltration (medicine goes into surrounding tissues), or if the patient feels burning or stinging:
- Immediately stop the infusion and disconnect it (but leave the needle or cannula in place).
- Gently remove any of the leaked solution (do not flush the line).
- Take out the needle or cannula.
- Elevate the affected area.
- Do not apply pressure to the site.
- Apply ice for 15 minutes, 4 times a day, for 3 days.

Mechanism of action of Pegylated liposomal doxorubicin (Doxil):

Doxorubicin messes with DNA and RNA, which are like the instruction manuals for cells.
It sneaks itself in between the building blocks of DNA, causing a kind of traffic jam that messes things up.
It also interferes with a molecule called topoisomerase-II, which helps DNA do its job.
Doxorubicin is like a ninja with iron; it grabs onto iron really well.
When it grabs iron, it can attach to DNA and cell coverings, and this produces harmful molecules called hydroxyl radicals.
These radicals can slice up DNA and cell coverings.
Doxorubicin stays active all throughout a cell's life cycle.
Doxorubicin liposomal is a special version that's wrapped up in a protective coating, so it stays in the bloodstream longer.

Doxorubicin Distribution:

The volume it spreads to in the body is around 2.7 to 2.8 liters for every square meter of body surface. This means it mostly stays in the blood and doesn't spread too far into body tissues.

Protein Binding:

We don't know how much of the drug sticks to proteins in the blood when it's in the liposomal form. But the regular form of doxorubicin binds to about 70% of the proteins.

How Long It Stays in the Body:

After being given, the amount in the body drops by half in about 4.7 to 5.2 hours.
But to fully get rid of half the drug, it takes around 52 to 55 hours.

How It's Processed (Metabolism):