Caelyx


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Related to Caelyx: Doxil, Myocet

doxorubicin hydrochloride, liposomal

Caelyx (CA) (UK), Doxil, Myocet (UK)

Pharmacologic class: Anthracycline

Therapeutic class: Antibiotic antineoplastic

Pregnancy risk category D

FDA Box Warning

• Drug may cause cardiotoxicity. Myocardial damage may lead to heart failure and may occur as total cumulative dose (which includes previous use of other anthracyclines or anthracenediones) approaches 550 mg/m2. Toxicity may occur at lower cumulative doses in patients who have had previous mediastinal irradiation or are receiving concurrent cyclophosphamides.

• Acute infusion-related reactions occur in up to 10% of patients. They usually resolve over several hours to 1 day after infusion ends; in some patients, they resolve with slower infusion rate. Serious and sometimes life-threatening allergic or anaphylactoid-like infusion reactions may occur. Keep emergency equipment and drugs to treat reaction available for immediate use.

• Drug may cause severe myelosuppression.

• Reduce dosage in hepatic impairment.

• Accidental substitution of liposomal form for doxorubicin hydrochloride may cause severe adverse effects. Don't substitute on mg-per-mg basis.

Action

Unclear. Thought to inhibit DNA and RNA synthesis by forming complex with DNA. Also exerts immunosuppressive activity. Liposomal encapsulation increases uptake by tumors, prolongs drug action, and may decrease toxicity. Cell-cycle-S-phase specific.

Availability

Liposomal dispersion for injection: 2 mg/ml in 10-ml vial, 2 mg/ml in 25-ml vials

Indications and dosages

AIDS-related Kaposi's sarcoma

Adults: 20 mg/m2 I.V. once q 3 weeks

Metastatic ovarian carcinoma

Adults: Initially, 50 mg/m2 I.V. at a rate of 1 mg/minute q 4 weeks for at least four courses. If no adverse reactions occur, increase infusion rate to complete the infusion over 1 hour.

Dosage adjustment

• Hepatic impairment

Contraindications

• Hypersensitivity to drug
• Malignant melanoma
• CNS metastases
• Bone marrow depression
• Cardiac disease
• Breastfeeding

Precautions

Use cautiously in:
• hepatic impairment, brain tumor, renal carcinoma, myelosuppression
• elderly patients
• females of childbearing age
• pregnant patients
• children.

Administration

• Follow facility policy for handling and preparing antineoplastics.
• Dilute dose (up to 90 mg) in 250 ml of dextrose 5% in water. Don't use any other diluent.

Don't dilute solution with bacteriostatic diluent. Don't mix with other drugs.
• Don't use in-line filter.
• Administer slowly by I.V. infusion at initial rate of 1 mg/minute. If no infusion reaction occurs, increase rate to complete infusion over 1 hour. Don't give as I.V. bolus.

Avoid rapid infusion, which may increase the risk of infusion-related reactions (back pain, chest tightness, flushing).

If extravasation occurs, stop infusion immediately, apply ice, and notify prescriber.
• Don't give I.M. or subcutaneously.
• Know that drug is a translucent red dispersion, not a clear solution.

Adverse reactions

CNS: drowsiness, dizziness, asthenia, fatigue, malaise, paresthesia, headache, depression, insomnia, anxiety, emotional lability

CV: chest pain, hypotension, tachycardia, peripheral edema, cardiomyopathy, heart failure, arrhythmias, pericardial effusion

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, enlarged abdomen, dyspepsia, moniliasis, stomatitis, glossitis, oral candidiasis, esophagitis, dysphagia

GU: albuminuria, red urine

Hematologic: anemia, leukopenia, thrombocytopenia, neutropenia, bone marrow depression

Hepatic: jaundice

Metabolic: hypocalcemia, hyperglycemia

Musculoskeletal: myalgia, back pain, hand-foot syndrome

Respiratory: dyspnea, increased cough, pneumonia

Skin: rash, dry skin, pruritus, skin discoloration, alopecia, diaphoresis, exfoliative dermatitis, palmar-plantar erythrodysesthesia

Other: altered taste, fever, chills, infection, herpes zoster, injection site reactions, allergic reactions including anaphylaxis, acute infusion reaction

Interactions

Drug-drug.Antineoplastics: additive bone marrow depression

Cyclophosphamide: increased risk of hemorrhagic cystitis

Cyclosporine: profound and prolonged hematologic toxicity, increased risk of coma and seizures, increased cardiotoxicity

Dactinomycin (in children): increased risk of pneumonitis

Live-virus vaccines: decreased antibody response to vaccine, increased risk of adverse reactions

Mercaptopurine: hepatitis

Paclitaxel (if administered first): reduced doxorubicin clearance, increased incidence and severity of neutropenia and stomatitis

Phenobarbital: increased clearance and decreased effects of doxorubicin

Phenytoin: decreased phenytoin blood level

Progesterone: increased risk and severity of neutropenia and thrombocytopenia

Streptozocin: prolonged doxorubicin half-life

Verapamil: increased doxorubicin blood level

Drug-diagnostic tests.Alkaline phosphatase, bilirubin, glucose, prothrombin time, serum and urine uric acid: increased levels

Calcium, hemoglobin, neutrophils, platelets, white blood cells: decreased levels

Patient monitoring

Observe patient closely for anaphylaxis and bleeding problems.

Stay alert for acute life-threatening arrhythmias, which may occur during or within a few hours after administration.

Assess for cardiomyopathy and subsequent heart failure with chronic overdose (more common in children).

Monitor closely for acute infusion reaction.
• Assess for and report liver engorgement and yellowing of skin or eyes.
• Check CBC, coagulation tests, hepatic profile, and bilirubin, glucose, calcium and uric acid levels.
• Watch for nausea and vomiting. Give antiemetics, as needed and prescribed.
• Assess for constipation and give fluids and stool softeners, as needed and prescribed.

Patient teaching

Instruct patient to immediately report shortness of breath; tingling or burning, redness, flaking, bothersome swelling, small blisters, or small sores on palms of hands or soles of feet; rash, chest pain, or palpitations.
• Advise patient to avoid people with colds, flu, or other contagious illnesses.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

DOXOrubicin

(dox-oh-roo-bi-sin) ,

Adriamycin

(trade name),

Caelyx

(trade name),

Myocet

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: anthracyclines
Pregnancy Category: D

Indications

Alone or with other modalities in the treatment of various solid tumors including:
  • Breast,
  • Ovarian,
  • Bladder,
  • Bronchogenic carcinoma,
  • Malignant lymphomas and leukemias.

Action

Inhibits DNA and RNA synthesis by forming a complex with DNA; action is cell-cycle S-phase–specific.
Also has immunosuppressive properties.

Therapeutic effects

Death of rapidly replicating cells, particularly malignant ones.

Pharmacokinetics

Absorption: Administered IV only, resulting in complete bioavailability.
Distribution: Widely distributed; does not cross the blood-brain barrier; extensively bound to tissues.
Metabolism and Excretion: Mostly metabolized by the liver (primarily by CYP2D6 and CYP3A4). Converted by liver to an active compound. Excreted predominantly in the bile, 50% as unchanged drug. Less than 5% eliminated unchanged in the urine.
Half-life: 16.7 hr.

Time/action profile (effect on blood counts)

ROUTEONSETPEAKDURATION
IV10 days14 days21–24 days

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Obstetric / Lactation: Pregnancy or lactation.
Use Cautiously in: History of cardiac disease or high cumulative doses of anthracyclines;Depressed bone marrow reserve;Liver impairment (reduce dose if serum bilirubin >1.2 m g/dL);Children, geriatric patients, mediastinal radiation, concurrent cyclophosphamide (↑ risk of cardiotoxicity); Obstetric: Patients with child-bearing potential.

Adverse Reactions/Side Effects

Respiratory

  • recall pneumonitis

Cardiovascular

  • cardiomyopathy (life-threatening)
  • ECG changes

Gastrointestinal

  • diarrhea (most frequent)
  • esophagitis (most frequent)
  • nausea (most frequent)
  • stomatitis (most frequent)
  • vomiting (most frequent)

Genitourinary

  • red urine (most frequent)

Dermatologic

  • alopecia (most frequent)
  • photosensitivity

Endocrinologic

  • sterility
  • prepubertal growth failure with temporary gonadal impairment (children only)

Hematologic

  • anemia (most frequent)
  • leukopenia (most frequent)
  • thrombocytopenia (most frequent)

Local

  • phlebitis at IV site (most frequent)
  • tissue necrosis

Metabolic

  • hyperuricemia

Miscellaneous

  • hypersensitivity reactions

Interactions

Drug-Drug interaction

CYP2D6 inhibitors, CYP3A4 inhibitors, and P-glycoprotein inhibitors may ↑ risk of toxicity; avoid concurrent useCYP2D6 inducers, CYP3A4 inducers, and P-glycoprotein inducers may ↓ effect and ↑ risk of therapeutic failure; avoid concurrent use↑ bone marrow depression with other antineoplastics or radiation therapy.Pediatric patients who have received concurrent doxorubicin and dactinomycin have an ↑ risk of recall pneumonitis at variable times following local radiation therapy.May ↑ skin reactions at previous radiation therapy sites.If paclitaxel is administered first, clearance of doxorubicin is ↓ and the incidence and severity of neutropenia and stomatitis are ↑ (problem is diminished if doxorubicin is administered first).Hematologic toxicity is ↑ and prolonged by concurrent use of cyclosporine ; risk of coma and seizures is also ↑.Incidence and severity of neutropenia and thrombocytopenia are ↑ by concurrent progesterone.Phenobarbital may ↑ clearance and decrease effects of doxorubicin.Doxorubicin may ↓ metabolism and ↑ effects of phenytoin.Streptozocin may ↑ the half-life of doxorubicin (dosage ↓ of doxorubicin recommended).May ↑ risk of hemorrhagic cystitis from cyclophosphamide.May ↑ risk of hepatotoxicity from mercaptopurine Cardiac toxicity may be ↑ by radiation therapy or cyclophosphamide.↑ risk of cardiac toxicity with trastuzumab ; avoid concurrent useIf dexrazoxane is administered at initiation of doxorubicin-containing regimens, may ↑ risk of therapeutic failure and tumor progressionMay ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.

Route/Dosage

Other regimens are used
Intravenous (Adults) 60–75 mg/m2 daily, repeat q 21 days; or 25–30 mg/m2 daily for 2–3 days, repeat q 3–4 wk or 20 mg/m2/wk. Total cumulative dose should not exceed 550 mg/m2 without monitoring of cardiac function or 400 mg/m2 in patients with previous chest radiation or other cardiotoxic chemotherapy.
Intravenous (Children) 30 mg/m2/day for 3 days every 4 wk.

Hepatic Impairment

Intravenous (Adults) Serum bilirubin 1.2–3mg/dL—50% of usual dose; serum bilirubin 3.1–5 mg/dL—25% of usual dose.

Availability (generic available)

Powder for injection: 10 mg/vial, 20 mg/vial, 50 mg/vial, 150 mg/vial
Solution for injection: 2 mg/mL

Nursing implications

Nursing assessment

  • Monitor BP, pulse, respiratory rate, and temperature frequently during administration. Report significant changes.
  • Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and taking rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.
  • Monitor intake and output ratios, and report occurrence of significant discrepancies. Encourage fluid intake of 2000–3000 mL/day. Allopurinol and alkalinization of the urine may be used to decrease serum uric acid levels and to help prevent urate stone formation.
  • Severe and protracted nausea and vomiting may occur as early as 1 hr after therapy and may last 24 hr. Administer parenteral antiemetics 30–45 min prior to therapy and routinely around the clock for the next 24 hr as indicated. Monitor amount of emesis and notify physician or other health care professional if emesis exceeds guidelines to prevent dehydration.
  • Monitor for development of signs of cardiac toxicity, which may be either acute and transient (ST segment depression, flattened T wave, sinus tachycardia, and extrasystoles) or late onset (usually occurs 1–6 mo after initiation of therapy) and characterized by intractable HF (peripheral edema, dyspnea, rales/crackles, weight gain). Chest x ray, echocardiography, ECGs, and radionuclide angiography may be ordered prior to and periodically during therapy. Cardiotoxicity is more prevalent in children younger than 2 yr and geriatric patients. Dexrazoxane may be used to prevent cardiotoxicity in patients receiving cumulative doses of >300 mg/m2.
  • Assess injection site frequently for redness, irritation, or inflammation during and for up to 2 hr after completion of infusion. Doxorubicin is a vesicant but may infiltrate painlessly even if blood returns on aspiration of infusion needle. Severe tissue damage may occur if doxorubicin extravasates. If extravasation occurs, stop infusion immediately, restart, and complete dose in another vein. Local infiltration of antidote is not recommended. Apply ice packs and elevate and rest extremity for 24–48 hr to reduce swelling, then resume normal activity as tolerated. May also use DMSO or dexrazoxane to treat extravasation. For DMSO: Apply dimethyl sulfoxide (DMSO) 99% by saturating a gauze pad and painting on an area twice the size of the extravasation. Allow site to air dry and repeat application every 6 hr for 14 days. Do not cover the area with dressing. For dexrazoxane: Administer first infusion as soon as possible within 6 hr of extravasation. Remove ice packs for at least 15 minutes prior to and during dexrazoxane administration. Recommended dose of dexrazoxane for day 1 is 1000 mg/m2 (up to 2000 mg), the dose for day 2 is 1000 mg/m2 (up to 2000 mg), and the dose for day 3 is 500 mg/m2 (up to 1000 mg). Dexrazoxane is administered as an IV infusion over 1 to 2 hr. Concurrent treatment with topical dimethyl sulfoxide application should not be used in conjunction with dexrazoxane, and if administered, may worsen extravasation-induced tissue injury. If swelling, redness, and/or pain persists beyond 48 hr, immediate consultation for possible debridement is indicated.
  • Assess oral mucosa frequently for development of stomatitis. Increased dosing interval and/or decreased dosing is recommended if lesions are painful or interfere with nutrition.
  • Lab Test Considerations: Monitor CBC and differential prior to and periodically during therapy. WBC nadir occurs 10–14 days after administration, and recovery usually occurs by the 21st day. Thrombocytopenia and anemia may also occur. Increased dosing interval and/or decreased dose is recommended if ANC is <1000 cells/mm3 and/or platelet count is <50,000 cells/mm3.
    • Monitor renal (BUN and creatinine) and hepatic (AST, ALT, LDH, and serum bilirubin) function prior to and periodically during therapy. Dose reduction is required for bilirubin >1.2 m g/dL or serum creatinine >3 m g/dL.
    • May cause ↑ serum and urine uric acid concentrations.

Potential Nursing Diagnoses

Risk for infection (Adverse Reactions)
Decreased cardiac output (Adverse Reactions)

Implementation

  • high alert: Fatalities have occurred with incorrect administration of chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations, and infusion pump settings.
  • high alert: Do not confuse doxorubicin hydrochloride with doxorubicin hydrochloride liposome (Doxil) or with daunorubicin hydrochloride (Cerubidine) or daunorubicin citrate liposome (DaunoXome) or with idarubicin. Clarify orders that do not include generic and brand names.
  • Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated containers (see ).
    • Aluminum needles may be used to administer doxorubicin but should not be used during storage, because prolonged contact results in discoloration of solution and formation of a dark precipitate. Solution is red.
  • Intravenous Administration
  • Diluent: Dilute each 10 mg with 5 mL of 0.9% NaCl (nonbacteriostatic) for injection. Shake to dissolve completely. Do not add to IV solution. Reconstituted medication is stable for 24 hr at room temperature and 48 hr if refrigerated. Protect from sunlight.Concentration: 2 mg/mL.
  • Rate: Administer each dose over 3–5 min through Y-site of a free-flowing infusion of 0.9% NaCl or D5W. Facial flushing and erythema along involved vein frequently occur when administration is too rapid.
  • Intermittent Infusion: Has also been mixed in 100–250 mL of 0.9% NaCl.
  • Rate: Infuse over 30–60 min.
  • Y-Site Compatibility: alemtuzumab, alfentanil, amifostine, amikacin, anidulafungin, argatroban, aztreonam, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, calcium chloride, calcium gluconate, carboplatin, carmustine, caspofungin, chlorpromazine, ciprofloxacin, cisplatin, cladribine, clindamycin, cyclophosphamide, cyclosporine, cytarabine, dactinomycin, daptomycin, dexamethasone, dexmedetomidine, dexrazoxane, diltiazem, diphenhydramine, dobutamine, docetaxel, dolasetron, dopamine, doripenem, doxycycline, droperidol, enalaprilat, ephedrine, epinephrine, erythromycin, esmolol, etoposide, etoposide phosphate, famotidine, fenoldopam, fentanyl, filgrastim, fluconazole, fludarabine, gemcitabine, gentamicin, granisetron, haloperidol, hydrocortisone, hydromorphone, ifosfamide, imipenem/cilastatin, irinotecan, isoproterenol, ketorolac, labetalol, leucovorin calcium, levorphanol, lidocaine, linezolid, lorazepam, mannitol, mechlorethamine, melphalan, meperidine, mesna, methotrexate, metoclopramide, metoprolol, metronidazole, midazolam, milrinone, mitomycin, morphine, moxifloxacin, nalbuphine, naloxone, nesiritide, nicardipine, nitroglycerin, nitroprusside, octreotide, ondansetron, oxaliplatin, paclitaxel, palonosetron, pamidronate, pancuronium, phenylephrine, potassium acetate, potassium chloride, procainamide, prochlorperazine, promethazine, propranolol, quinupristin/dalfopristin, ranitidine, sargramostim, sodium acetate, sufentanil, tacrolimus, teniposide, theophylline, thiotepa, ticarcillin/clavulanate, tigecycline, tirofiban, tobramycin, topotecan, trastuzumab, vancomycin, vasopression, vecuronium, verapamil, vinblastine, vincristine, vinorelbine, zidovudine, zoledronic acid
  • Y-Site Incompatibility: acyclovir, allopurinol, aminophylline, amiodarone, amphotericin B cholesteryl, amphotericin B colloidal, amphotericin B lipid complex, amphotericin B liposome, ampicillin, ampicillin/sulbactam, cefazolin, cefepime, cefoperazone, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, diazepam, digoxin, ertapenem, foscarnet, fosphenytoin, ganciclovir, magnesium sulfate, meropenem, methohexital, pantoprazole, pemetrexed, pentamidine, pentobarbital, phenobarbital, phenytoin, piperacillin/tazobactam, potassium phosphates, propofol, rituximab, sodium phosphates, thiopental, trimethoprim/sufamethoxazole, voriconazole

Patient/Family Teaching

  • Instruct patient to notify health care professional promptly if fever; sore throat; signs of infection; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; increased fatigue; dyspnea; or orthostatic hypotension occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs, because these may precipitate gastric bleeding.
  • Instruct patient to report pain at injection site immediately.
  • Instruct patient to inspect oral mucosa for erythema and ulceration. If ulceration occurs, advise patient to use sponge brush, rinse mouth with water after eating and drinking, and confer with health care professional if mouth pain interferes with eating. Pain may require treatment with opioid analgesics. The risk of developing stomatitis is greatest 5–10 days after a dose; the usual duration is 3–7 days.
  • Instruct patient to notify health care professional immediately if irregular heartbeat, shortness of breath, swelling of lower extremities, or skin irritation (swelling, pain, or redness of feet or hands) occurs.
  • Discuss the possibility of hair loss with patient. Explore methods of coping. Regrowth usually occurs 2–3 mo after discontinuation of therapy.
  • Instruct patient not to receive any vaccinations without advice of health care professional.
  • Inform patient that medication may cause urine to appear red for 1–2 days.
  • Instruct patient to notify health care professional if skin irritation occurs at site of previous radiation therapy.
  • Advise family and/or caregivers to take precautions (i.e., latex gloves) in handling body fluids for at least 5 days post-treatment.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other Rx, OTC, or herbal products.
  • Inform patient that doxorubicin may increase risk of developing secondary cancers.
  • Advise patient that this medication may have teratogenic effects. Contraception should be used during and for at least 4 mo after therapy is concluded. Inform patient before initiating therapy that this medication may cause irreversible gonadal suppression.
  • Emphasize the need for periodic lab tests to monitor for side effects.

Evaluation/Desired Outcomes

  • Decrease in size or spread of malignancies in solid tumors.
  • Improvement of hematologic status in leukemias.

Caelyx

A brand name for DOXORUBICIN.
References in periodicals archive ?
CAELYX is also approved in the EU for the treatment of advanced ovarian cancer in women who have failed first-line, platinum-based therapy and for the treatment of AIDS-related Kaposi's sarcoma in patients with low CD4 counts (<200 CD4 lymphocytes/mm3) and extensive mucocutaneous or visceral disease and in combination with VELCADE(R) (bortezomib) for the treatment of progressive multiple myeloma in patients who have received at least one prior therapy and who have already undergone or are unsuitable for bone marrow transplant.
These results support further evaluation of CAELYX plus carboplatin in patients with advanced ovarian cancer," said Robert J.
The study evaluated the efficacy and safety of CAELYX and carboplatin in 104 treated patients (out of 105 enrolled) with advanced ovarian cancer who had relapsed six months or more after first- or second-line treatment.
Patients received CAELYX 30 mg/m(2) followed by carboplatin (AUC 5 mg.
Based on data from Phase II trials with YONDELIS as a monotherapy in relapsed ovarian cancer patients, and in Phase I trials with YONDELIS in combination with CAELYX (DOXIL), we believe we may be able to provide a new option to these patients.
As the combination of YONDELIS with CAELYX (DOXIL) also demonstrated activity and tolerability in a previous study(2), the study's theoretical premise is that the combination of two active drugs may improve the survival rate of the target patient population.
CAELYX, developed and owned by SEQUUS, is a long-circulating STEALTH(R) liposome formulation of doxorubicin, an anticancer drug.
The agreement provides for a joint development team to coordinate the clinical development of CAELYX for the oncology market.
As previously announced, CAELYX has received marketing clearance from the European Commission and, therefore, Schering-Plough will commence the marketing of CAELYX in certain European Union (EU) countries and will apply for pricing approvals from individual EU countries where required.
As part of the agreement, SEQUUS and Schering-Plough will jointly develop a worldwide clinical plan for investigating the use of CAELYX in the treatment of solid tumors.
On June, 25, 1996, the drug was approved for therapy of AIDS-KS patients in the 15 member nations of the European Union, where it will be marketed as CAELYX (TM).
This authorization allows us to immediately begin marketing CAELYX in those EU countries that do not require formal pricing applications, including the United Kingdom, Germany, Denmark and Sweden," said Carl F.