Nudoxa PEG

Each ml contains: Doxorubicin Hydrochloride (as Pegylated Liposomal) 2 mg.
Water for Injection q.s.
Doxorubicin hydrochloride liposome injection is doxorubicin hydrochloride, an anthracycline topoisomerase inhibitor, that is encapsulated in pegylated liposomes for intravenous use. The chemical name of doxorubicin hydrochloride is (8S,10S)-10-[(3-amino-2,3,6-trideoxy-α-L-lyxohexopyranosyl)oxy]-8-glycolyl-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5,12-naphthacenedione hydrochloride. The molecular formula is C₂₇H₂₉NO₁₁·HCl and the molecular weight is 579.99.
Doxorubicin hydrochloride liposome injection is a sterile, translucent, red liposomal dispersion. Each single dose vial contains 20 mg or 50 mg doxorubicin hydrochloride at a concentration of 2 mg/mL (equivalent to 1.87 mg/mL of doxorubicin) and a pH of 6.5. The pegylated liposome carriers are composed of cholesterol, 3.19 mg/mL; fully hydrogenated soy phosphatidylcholine (HSPC), 9.58 mg/mL; and N-(carbonylmethoxypolyethylene glycol 2,000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine sodium salt (MPEGDSPE), 3.19 mg/mL. Each mL also contains ammonium sulfate, approximately 0.6 mg; histidine as a buffer; hydrochloric acid and/or sodium hydroxide for pH control; and sucrose to maintain isotonicity. Greater than 90% of the drug is encapsulated in the pegylated liposomes.

Pharmacotherapeutic group: Anthracyclines and related substances. ATC code: L01DB01.
Pharmacology: Pharmacodynamics: Mechanism of action: The active ingredient of doxorubicin hydrochloride liposome injection is doxorubicin hydrochloride. The mechanism of action of doxorubicin hydrochloride is thought to be related to its ability to bind DNA and inhibit nucleic acid synthesis. Cell structure studies have demonstrated rapid cell penetration and perinuclear chromatin binding, rapid inhibition of mitotic activity and nucleic acid synthesis, and induction of mutagenesis and chromosomal aberrations.
Pharmacokinetic: The pharmacokinetic parameters for total doxorubicin following a single dose of doxorubicin hydrochloride liposome injection infused over 30 minutes are presented in Table 1. (See Table 1.)

Click on icon to see table/diagram/image

Doxorubicin hydrochloride liposome injection displayed linear pharmacokinetics over the range of 10 to 20 mg/m². Relative to doxorubicin hydrochloride liposome injection doses at or below 20 mg/m², the pharmacokinetics of total doxorubicin following a 50 mg/m² doxorubicin hydrochloride liposome injection dose are nonlinear. At this dose, the elimination half-life of doxorubicin hydrochloride liposome injection is longer and the clearance lower compared to a 20 mg/m² dose.
Distribution: Direct measurement of liposomal doxorubicin shows that at least 90% of the drug (the assay used cannot quantify less than 5-10% free doxorubicin) remains liposome-encapsulated during circulation.
In contrast to doxorubicin, which displays a large volume of distribution (range 700 to 1,100 L/m²), the small steady state volume of distribution of liposomal doxorubicin suggests that doxorubicin hydrochloride liposome injection is largely confined to vascular fluid. Doxorubicin becomes available after the liposomes are extravasated. Plasma protein binding of doxorubicin hydrochloride liposome injection has not been determined; the plasma protein binding of doxorubicin is approximately 70%.
Metabolism: Doxorubicinol, the major metabolite of doxorubicin, was detected at concentrations of 0.8 to 26.2 ng/mL in the plasma of patients who received 10 or 20 mg/m² doxorubicin hydrochloride liposome injection.
Elimination: The plasma clearance of total doxorubicin from doxorubicin hydrochloride liposome injection was 0.041 L/h/m² at a dose of 20 mg/m². Following administration of doxorubicin hydrochloride, the plasma clearance of doxorubicin is 24 to 35 L/h/m².

Ovarian Cancer: Doxorubicin hydrochloride liposome injection is indicated for the treatment of patients with ovarian cancer whose disease has progressed or recurred after platinum-based chemotherapy.
AIDS-Related Kaposi's Sarcoma: Doxorubicin hydrochloride liposome injection is indicated for the treatment of AIDS-related Kaposi's sarcoma in patients after failure of prior systemic chemotherapy or intolerance to such therapy.
Multiple Myeloma: Doxorubicin hydrochloride liposome injection, in combination with bortezomib, is indicated for the treatment of patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy.

Important Use Information: Do not substitute doxorubicin hydrochloride liposome injection for other doxorubicin hydrochloride products.
Do not administer as an undiluted suspension or as an intravenous bolus.
Ovarian Cancer: The recommended dose of doxorubicin hydrochloride liposome injection is 50 mg/m² intravenously over 60 minutes every 28 days until disease progression or unacceptable toxicity.
AIDS-Related Kaposi's Sarcoma: The recommended dose of doxorubicin hydrochloride liposome injection is 20 mg/m² intravenously over 60 minutes every 21 days until disease progression or unacceptable toxicity.
Multiple Myeloma: The recommended dose of doxorubicin hydrochloride liposome injection is 30 mg/m² intravenously over 60 minutes on day 4 of each 21-day cycle for eight cycles or until disease progression or unacceptable toxicity. Administer doxorubicin hydrochloride liposome injection after bortezomib on day 4 of each cycle.
Dose Modifications for Adverse Reactions: Do not increase doxorubicin hydrochloride liposome injection after a dose reduction for toxicity. (See Tables 2 and 3.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

For neuropathic pain or peripheral neuropathy, no dosage adjustments are required for doxorubicin hydrochloride liposome injection. Refer to bortezomib manufacturer's prescribing information.
Method of administration: Preparation: Dilute doxorubicin hydrochloride liposome injection doses up to 90 mg in 250 mL of 5% Dextrose Injection, USP prior to administration. Dilute doses exceeding 90 mg in 500 mL of 5% Dextrose Injection, USP prior to administration. Refrigerate diluted doxorubicin hydrochloride liposome injection at 2°C to 8°C (36°F to 46°F) and administer within 24 hours.

Symptoms: Acute overdosage with doxorubicin hydrochloride causes increased risk of severe mucositis, leukopenia, and thrombocytopenia.
Treatment: No information available.

Doxorubicin hydrochloride liposome injection is contraindicated in patients who have a history of severe hypersensitivity reactions, including anaphylaxis, to doxorubicin hydrochloride.

Cardiomyopathy: Doxorubicin hydrochloride can cause myocardial damage, including acute left ventricular failure. The risk of cardiomyopathy with doxorubicin hydrochloride is generally proportional to the cumulative exposure. Include prior use of other anthracyclines or anthracenediones in calculations of cumulative dose. The risk of cardiomyopathy may be increased at lower cumulative doses in patients with prior mediastinal irradiation.
Assess left ventricular cardiac function (e.g. MUGA or echocardiogram) prior to initiation of doxorubicin hydrochloride liposome injection, during treatment to detect acute changes, and after treatment to detect delayed cardiomyopathy. Administer doxorubicin hydrochloride liposome injection to patients with a history of cardiovascular disease only when the potential benefit of treatment outweighs the risk.
Infusion-Related Reactions: Serious, life-threatening, and fatal infusion-related reactions characterized by one or more of the following symptoms can occur with doxorubicin hydrochloride liposome injection: flushing, shortness of breath, facial swelling, headache, chills, chest pain, back pain, tightness in the chest and throat, fever, tachycardia, pruritus, rash, cyanosis, syncope, bronchospasm, asthma, apnea, and hypotension.
Ensure that medications to treat infusion-related reactions and cardiopulmonary resuscitative equipment are available for immediate use prior to initiation of doxorubicin hydrochloride liposome injection. Initiate doxorubicin hydrochloride liposome injection infusions at a rate of 1 mg/min and increase rate as tolerated. Withhold doxorubicin hydrochloride liposome injection infusion for Grade 1, 2, or 3 infusion-related reactions and resume at a reduced infusion rate. Discontinue doxorubicin hydrochloride liposome injection infusion for serious or life-threatening infusion-related reactions.
Hand-Foot Syndrome (HFS): HFS was generally observed after 2 or 3 cycles of treatment but may occur earlier. Delay doxorubicin hydrochloride liposome injection for the first episode of Grade 2 or greater HFS. Discontinue doxorubicin hydrochloride liposome injection if HFS is severe and debilitating.
Secondary Oral Neoplasms: Secondary oral cancers, primarily squamous cell carcinoma, have been reported from post-marketing experience in patients with long-term (more than one year) exposure to doxorubicin hydrochloride liposome injection. These malignancies were diagnosed both during treatment with doxorubicin hydrochloride liposome injection and up to 6 years after the last dose. Examine patients at regular intervals for the presence of oral ulceration or with any oral discomfort that may be indicative of secondary oral cancer. The altered pharmacokinetics and preferential tissue distribution of liposomal doxorubicin that contributes to enhanced skin toxicity and mucositis compared to free doxorubicin may play a role in the development of oral secondary malignancies with long-term use.
Embryo-Fetal Toxicity: Based on findings in animals and its mechanism of action, doxorubicin hydrochloride liposome injection can cause fetal harm when administered to a pregnant woman; avoid the use of doxorubicin hydrochloride liposome injection during the 1st trimester. Available human data do not establish the presence or absence of major birth defects and miscarriage related to the use of doxorubicin hydrochloride during the 2nd and 3rd trimesters. At doses approximately 0.12 times the recommended clinical dose, doxorubicin hydrochloride liposome injection was embryotoxic and abortifacient in rabbits. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during and for 6 months after treatment with doxorubicin hydrochloride liposome injection.

Pregnancy: Based on findings in animals and its mechanism of action, doxorubicin hydrochloride liposome injection can cause fetal harm when administered to a pregnant woman; avoid the use of doxorubicin hydrochloride liposome injection during the 1st trimester In animal reproduction studies, doxorubicin hydrochloride liposome injection was embryotoxic in rats and abortifacient in rabbits following intravenous administration during organogenesis at doses approximately 0.12 times the recommended clinical dose. Available human data do not establish the presence or absence of major birth defects and miscarriage related to the use of doxorubicin hydrochloride during the 2nd and 3rd trimesters. Advise pregnant women of the potential risk to a fetus.
Breastfeeding: It is not known whether doxorubicin hydrochloride is present in human milk. Because many drugs, including anthracyclines, are excreted in human milk and because of the potential for serious adverse reactions in breastfed infants from doxorubicin hydrochloride liposome injection, discontinue breastfeeding during treatment with doxorubicin hydrochloride liposome injection.
Fertility: Females: In females of reproductive potential, doxorubicin hydrochloride liposome injection may cause infertility and result in amenorrhea. Premature menopause can occur with doxorubicin hydrochloride. Recovery of menses and ovulation is related to age at treatment.
Males: Doxorubicin hydrochloride liposome injection may result in oligospermia, azoospermia, and permanent loss of fertility. Sperm counts have been reported to return to normal levels in some men. This may occur several years after the end of therapy.

The following adverse reactions are discussed in more detail in other sections of the monograph: Cardiomyopathy [see Precautions]; Infusion-Related Reactions [see Precautions]; Hand-Foot Syndrome [see Precautions]; Secondary Oral Neoplasms [see Precautions].

No formal drug interaction studies have been conducted with doxorubicin hydrochloride liposome injection.

Administration: Inspect parenteral drug products visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if a precipitate or foreign matter is present.
Do not use with in-line filters.
Administer the first dose of doxorubicin hydrochloride liposome injection at an initial rate of 1 mg/min. If no infusion-related adverse reactions are observed, increase the infusion rate to complete the administration of the drug over one hour. Do not rapidly flush the infusion line.
Do not mix doxorubicin hydrochloride liposome injection with other drugs.
Management of Suspected Extravasation: Discontinue doxorubicin hydrochloride liposome injection for burning or stinging sensation or other evidence indicating perivenous infiltration or extravasation. Manage confirmed or suspected extravasation as follows: Do not remove the needle until attempts are made to aspirate extravasated fluid.
Do not flush the line.
Avoid applying pressure to the site.
Apply ice to the site intermittently for 15 min 4 times a day for 3 days.
If the extravasation is in an extremity, elevate the extremity.

Store between 2°C to 8°C. Do not freeze.
Discard unused portion.

Cytotoxic Chemotherapy

L01DB01 - doxorubicin ; Belongs to the class of cytotoxic antibiotics, anthracyclines and related substances. Used in the treatment of cancer.

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