Name of the Anti-tumor antibiotics-Anthracyclines drugs
- Daunorubicin
- Doxorubicin
- Idarubicin
1.Daunorubicin
| DAUNORUBICIN |
| Availability: Injection Solution: (Cerubidine): 5 mg/mL.; Injection Solution: (DaunoXome): 2 mg/mL. |
| Administration/handling: IV (Cerubidine) Give by IV push or IV infusion. Reconstitution • May further dilute with 100 mL D5W or 0.9% NaCl. Rate of administration • For IV push, withdraw desired dose into syringe containing 10–15 mL 0.9% NaCl. Inject over 1–5 min into tubing of rapidly infusing IV solution of D5W or 0.9% NaCl. • For IV infusion, further dilute with 100 mL D5W or 0.9% NaCl. Infuse over 15–30 min. • Extravasation produces immediate pain, severe local tissue damage. Aspirate as much infiltrated drug as possible, then infiltrate area with hydrocortisone sodium succinate injection (50–100 mg hydrocortisone) and/or isotonic sodium thiosulfate injection or ascorbic acid injection (1 mL of 5% injection). Apply cold compresses. Storage • Refrigerate intact vials. • Protect from light. • Solutions prepared for infusion stable for 24 hrs at room temperature. |
| Cumulative dose should not exceed 550 mg/m2 in adults (increased risk of cardiotoxicity) or 400 mg/m2 in those receiving chest irradiation. |
| Acute Lymphocytic Leukemia: IV: Adults, elderly: 45 mg/m2 on days 1, 2, and 3 (in combination with vincristine, prednisone, asparaginase). Children 2 yrs and older and body surface area 0.5 m2 OR Greater: 25 mg/m2 on day 1 of every wk for up to 4–6 cycles (in combination with vinCRIStine, predniSONE). Children younger than 2 yrs, or body surface area less than 0.5 m2: 1 mg/kg/dose on day 1 of every wk for up to 4 to 6 cycles (in combination with vincristine, prednisone |
| Acute Myeloid Leukemia : IV: Adults younger than 60 yrs: 45mg/m2 on days 1, 2, and 3 of induction course, then on days 1 and 2 of subsequent courses (in combination with cytarabine). Adults 60 yrs and older: 30 mg/m2 on days 1, 2, and 3 of induction course, then on days 1 and 2 of subsequent courses (in combination with cytarabine). |
Mechanism of action:
Inhibits DNA and RNA synthesis by intercalation between DNA base pairs and by steric obstruction. Cell cycle–phase nonspecific.
Therapeutic Effect: Prevents cell division.
Indications:
- Treatment of leukaemia’s (acute lymphocytic [ALL] acute myeloid [AML]) in combination with other agents
Cautions & Contraindications:
- Hypersensitivity to Daunorubicin.
Cautions:
- Preexisting heart disease or bone marrow suppression, hypertension, concurrent chemotherapeutic agents, elderly, infants, radiation therapy
Metabolism and Half- life:
- Widely distributed.
- Protein binding: High.
- Does not cross blood-brain barrier.
- Metabolized in liver. Excreted in urine (40%); biliary excretion (40%).
- Half-life: 18.5 hrs; metabolite: 26.7 hrs.
Drug Interactions:
- Bevacizumab, cyclophosphamide: may increase risk of cardiotoxicity.
- Bone marrow depressants (e.g., cladribine) may enhance myelosuppression.
- Live virus vaccines may potentiate virus replication increase vaccine side effects, decrease pt’s antibody response to vaccine.
- May increase serum alkaline phosphatase, bilirubin, uric acid, AST
Side- Effects:
- Frequent: Complete alopecia (scalp, axillary, pubic), nausea, vomiting (beginning a few hrs after administration and lasting 24–48 hrs).
- Occasional: Diarrhoea, abdominal pain, esophagitis, stomatitis, transverse pigmentation of fingernails, toenails.
- Rare: Transient fever, chill
Nursing Considerations
Baseline assessment
- Obtain CBC, LFT; BUN, serum creatinine, CrCl, GFR in pts with renal impairment.
- Obtain ECG before initiation, esp. in pts with cardiac disease.
- Antiemetics may be effective in preventing, treating nausea.
- Ensure patency of IV access.
- Obtain accurate height and weight for dose calculation.
- Offer emotional support.
Intervention/evaluation
- Obtain CBC frequently; BMP, LFT, serum uric acid periodically.
- Monitor daily pattern of bowel activity, stool consistency.
- Monitor for hematologic toxicity (fever, sore throat, signs of local infection, unusual bruising/bleeding from any site)
- symptoms of anaemia (excessive fatigue, weakness).
- Diligently monitor for extravasation, tissue necrosis.
- Evaluate CBC with white cell differential before each dose. Withhold dose if granulocyte count is below 750 cells/mm3.
- Monitor serum uric acid level.
Patient/family teaching
- Urine may turn reddish colour for 1–2 days after beginning therapy.
- Hair loss is reversible, but new hair growth may have different colour, texture. New hair growth resumes about 5 weeks after last therapy dose
- Maintain strict oral hygiene.
- Do not have immunizations without physician’s approval (drug lowers resistance).
- Avoid contact with those who have recently received live virus vaccine.
- Promptly report fever, sore throat, signs of local infection, unusual bruising/bleeding from any site, yellowing of whites of eyes/skin, difficulty breathing.
- Report persistent nausea, vomiting.
- Treatment may impair the heart’s ability to pump blood effectively; report difficulty breathing, chest pain, palpitations, swelling of the legs or feet.
- Inform patient that drug makes him more susceptible to infection. Caution him to avoid crowds and exposure to illness.
- Advise patient to minimize GI upset by eating small, frequent servings of healthy food, drinking plenty of fluids and chewing gum
2.Doxorubicin
| DOXORUBICIN |
| Availability: Injection, Powder for Reconstitution: 10 mg, 20 mg, 50 mg. Injection Solution: (Adriamycin): 2 mg/mL (5-mL, 10-mL, 25-mL, 100-mL vial). Lipid Complex: (Doxil, Lipodox-50): 2 mg/mL (10 mL, 25 mL). |
| Administration/handling: Wear gloves. If powder or solution comes into contact with skin, wash thoroughly. Avoid small veins; swollen/oedematous extremities; areas overlying joints, tendons. • (Doxil): Do not use with in-line filter or mix with any diluent except D5W. May be carcinogenic, mutagenic, teratogenic. Handle with extreme care during preparation/administration. |
| IV: Reconstitution • Reconstitute vials of powder with 0.9% NaCl to provide concentration of 2 mg/mL. • Shake vial; allow contents to dissolve. • Withdraw appropriate volume of air from vial during reconstitution (avoids excessive pressure buildup). • May be further diluted with 50–1,000 mL D5W or 0.9% NaCl and given as continuous infusion. • (Doxil): Dilute each dose in 250 mL D5W (doses greater than 90 mg in 500 mL D5W). Rate of administration • (Adriamycin): For IV push, administer into tubing of freely running IV infusion of D5W or 0.9% NaCl, preferably via butterfly needle over 3–5 min (avoids local erythematous streaking along vein and facial flushing). • Must test for flashback q30sec to be certain needle remains in vein during injection. IV piggyback over 15–60 min or continuous infusion. • Extravasation produces immediate pain, severe local tissue damage. Terminate administration immediately; withdraw as much medication as possible, obtain extravasation kit, follow protocol. • (Doxil): Give as infusion over 60 min. Do not use in-line filter |
| Storage • (Adriamycin powder): Store at room temperature. • Reconstituted vials stable for 7 days at room temperature, 15 days if refrigerated. Infusions stable for 48 hrs at room temperature. Protect from prolonged exposure to sunlight; discard unused solution. • (Adriamycin solution): Refrigerate vials. Solutions diluted in D5W or 0.9% NaCl stable for 48 hrs at room temperature. • (Doxil): Refrigerate unopened vials. After solution is diluted, use within 24 hrs. |
| Usual Dosage: IV: (Adriamycin): Adults: (Single-agent therapy): 60–75 mg/m2 as a single dose every 21 days, 20mg/m2 once wkly. (Combination therapy): 40–75 mg/m2 q21–28 days. Because of risk of cardiotoxicity, do not exceed cumulative dose of 550 mg/m2 (400–450 mg/m2 for those previously treated with related compounds or irradiation of cardiac region). CHILDREN: (Single- agent therapy): 60–75 mg/m2 q3wks. (Combination therapy): 40– 75 mg/m2 q21–28 days. |
| Kaposi’s Sarcoma: IV: (Doxil, Lipodox): Adults: 20 mg/m2 q3wks infused over 30 min. Continue until disease progression or unacceptable toxicity |
| Ovarian Cancer: IV: (Doxil, Lipodox): Adults: 50 mg/m2 q4wks. Continue until disease progression or unacceptable toxicity |
| Multiple Myeloma: IV: (Doxil, Lipodox): Adults: 30 mg/m2/dose on day 4 q3wks (in combination with bortezomib). Continue until disease progression or unacceptable toxicity |
| Solid tumors, including bladder, breast, lung, stomach, and thyroid cancers; malignant lymphomas, including Hodgkin’s disease; acute leukaemia; chronic lymphocytic leukaemia; multiple myeloma; Wilms’ tumour; neuroblastoma: Adults: 60 to 75 mg/m2 I.V. as a single dose at 21-day cycles, or 30 mg/m2 I.V. as a single daily dose on first to third days of 4-week cycle, or 20 mg/m2 I.V. once weekly. Maximum cumulative dosage is 550 mg/m2. |
| Follow facility policy for handling and preparing antineoplastics. Don’t dilute solution with bacteriostatic diluent. Don’t mix with other drugs. Dilute as directed with normal saline solution to a final concentration of 2 mg/ml. Administer slowly over 3 to 5 minutes into tubing of free-flowing I.V. infusion of normal saline solution or dextrose 5% in water. Deliver into large vein using butterfly needle. Avoid veins over joints or extremities with compromised venous or lymphatic drainage. Avoid rapid infusion, because this may increase risk of acute infusion related reactions (back pain, chest tightness, flushing). If extravasation occurs, stop infusion immediately, apply ice, and notify prescriber. |
Mechanism of Action:
Inhibits DNA, RNA synthesis by binding with DNA strands. Liposomal encapsulation increases uptake by tumours, prolongs drug action, may decrease toxicity. Therapeutic
Effect: Prevents cell division.
Indications:
- Adriamycin: Treatment of acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), Hodgkin’s lymphoma, malignant lymphoma; breast, gastric, small-cell lung, ovarian, epithelial, thyroid, bladder carcinomas; neuroblastoma, Wilms tumor, osteosarcoma, soft tissue sarcoma.
- Doxil, Lipodox: Treatment of AIDS-related Kaposi’s sarcoma, advanced ovarian cancer. Used with bortezomib to treat multiple myeloma in pts who have not previously received bortezomib and have received at least one previous treatment.
OFF-LABEL:
- Adriamycin: Multiple myeloma, endometrial carcinoma, uterine sarcoma; head and neck cancer, liver, kidney cancer.
- Doxil: Metastatic breast cancer, Hodgkin’s lymphoma, cutaneous T-cell lymphomas, advanced soft tissue sarcomas, recurrent or metastatic cervical cancer, advanced or metastatic uterine sarcoma
Cautions & Contraindications:
- Hypersensitivity to Doxorubicin.
Adriamycin:
- Severe hepatic impairment, severe myocardial insufficiency, recent MI (within 4–6 wks), severe arrhythmias.
- Previous or concomitant treatment with high accumulative doses of Doxorubicin, Daunorubicin, Idarubicin, or other anthracyclines or anthracenediones
- severe, persistent drug-induced myelosuppression or baseline ANC count less than 1,500 cells/mm3.
Doxil: Breastfeeding
Cautions:
- Hepatic impairment. Cardiomyopathy, preexisting myelosuppression, severe HF. Pts who received radiation therapy.
Metabolism and Half- Life:
- Widely distributed. Protein binding: 74%–76%. Does not cross blood-brain barrier.
- Metabolized in liver. Primarily eliminated by biliary system. Not removed by haemodialysis.
- Half-life: 20–48 hrs
Drug Interactions:
- Cyclosporine may increase concentration/effect, risk of hematologic toxicity.
- Bevacizumab, Daunorubicin may increase risk of cardiotoxicity.
- Bone marrow depressants (e.g., cladribine) may increase myelosuppression.
- Strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin) may decrease concentration/effect.
- Strong CYP3A4 inhibitors (e.g., clarithromycin, ketoconazole, ritonavir) may increase concentration/effect.
- Live virus vaccines may potentiate virus replication, increase vaccine side effects, decrease pt’s antibody response to vaccine.
- May cause ECG changes, increase serum uric acid.
- May reduce neutrophil, RBC counts.
Side- Effects:
Frequent:
- Complete alopecia (scalp, axillary, pubic hair), nausea, vomiting, stomatitis, esophagitis (esp. if drug is given on several successive days), reddish urine.
- Doxil: Nausea.
Occasional:
- Anorexia, diarrhea; hyperpigmentation of nailbeds, phalangeal, dermal creases.
Rare:
- Fever, chills, conjunctivitis, lacrimation.
Myelosuppression manifested as hematologic toxicity (principally leukopenia and, to lesser extent, anemia, thrombocytopenia) generally occurs within 10–15 days, returns to normal levels by third wk. Cardiotoxicity (either acute, manifested as transient ECG abnormalities, or chronic, manifested as HF) may occur
Nursing Considerations
Baseline assessment
- Obtain ANC, CBC, erythrocyte counts before and at frequent intervals during therapy.
- Obtain ECG before therapy, LFT before each dose.
- Antiemetics may be effective in preventing, treating nausea.
- Offer emotional support.
Intervention/evaluation
- Monitor for stomatitis (burning or erythema of oral mucosa at inner margin of lips, difficulty swallowing).
- Observe IV injection site for infiltration, vein irritation.
- May lead to ulceration of mucous membranes within 2–3 days.
- Assess dermal creases, nailbeds for hyperpigmentation.
- Monitor hematologic status, renal/hepatic function studies, serum uric acid levels.
- Monitor daily pattern of bowel activity, stool consistency.
- Monitor for hematologic toxicity (fever, sore throat, signs of local infection, unusual bruising/ bleeding from any site), symptoms of anaemia (excessive fatigue, weakness).
- Watch for acute life-threatening arrhythmias, which may occur during or within a few hours after administration.
- Monitor for cardiomyopathy and subsequent heart failure with chronic overdose (more common in children).
- Stay alert for erythematous streaking along vein next to injection site, which may indicate too-rapid infusion.
- Watch for nausea and vomiting.
- Administer antiemetics as needed.
- Check for superinfection or haemorrhage caused by persistent bone marrow depression (but expect WBC counts as low as 1,000/mm3 during therapy).
- Watch closely for infusion-related reactions and anaphylaxis.
- Monitor CBC, hepatic profile, coagulation tests, ejection fraction, and glucose, uric acid, bilirubin, and calcium blood levels.
Patient/family teaching
- Hair loss is reversible, but new hair growth may have different colour, texture. New hair growth resumes 2–3 months after last therapy dose.
- Maintain strict oral hygiene.
- Do not have immunizations without physician’s approval (drug lowers resistance).
- Avoid contact with those who have recently received live virus vaccine.
- Promptly report fever, sore throat, signs of local infection, unusual bruising/bleeding from any site.
- Report persistent nausea/vomiting.
- Avoid alcohol (may cause GI irritation, a common side effect with liposomal Doxorubicin).
- Advise patient to promptly report irregular heartbeats, easy bruising or bleeding, or signs of hypersensitivity reaction, such as a rash.
- Caution patient to avoid people with colds, flu, or other contagious illnesses.
- Inform patient that drug may turn urine red for 1 or 2 days.
3.Idarubicin
| IDARUBICIN |
| Availability: Injection: 1 mg/ml |
| Administration And handling: IV Preparation: Vials: reconstitute with NS to a concentration of 1 mg/mL Standard dilution: IV push: dose/syringe (concentration is 1 mg/mL); maximum syringe size for IVP is 30 mL syringe & syringe should be <75% full :IVPB: dose/100 mL D5W or NS IV Administration: Vesicant – Administer by intermittent infusion over 10-15 min; Administer into a free flowing IV solution of NS or D5W; Local erythematous streaking along the vein may indicate rapid administration |
| Extravasation Management: Topical cooling may be achieved using ice packs or cooling pad with circulating ice water Cooling of site for 25 hr as tolerated by pt. Elevate & rest extremity 24-48 hr, then resume normal activity as tolerated Cold inhibits vesicant’s cytotoxicity. Heat can be harmful & is contraindicated. If pain, erythema, &/or swelling persist beyond 48 hr, refer pt immediately to plastic surgeon for consultation & possible debridement |
| Storage: Store intact vials of lyophilized powder at room temp; Protect from light |
| When preparing, wear goggles and gloves, because exposure may cause severe skin reaction. If exposure occurs, wash affected area immediately with soap and water. For eye exposure, follow standard eye irrigation procedure. Reconstitute 5-, 10-, or 20-mg vial with 5, 10, or 20 ml of normal saline solution, respectively, to yield a concentration of 1 mg/ml. Give slowly over 10 to 15 minutes into I.V. tubing that is infusing normal saline solution or dextrose 5% in water. Don’t administer subcutaneously or I.M. (may cause tissue necrosis). If severe mucositis occurs, delay second course (if prescribed) until full recovery; then reduce dosage by 25%. |
| Acute myeloid leukaemia : Adults: 12 mg/m2/day by slow I.V. injection over 10 to 15 minutes for 3 days. As prescribed, give with cytarabine by continuous I.V. infusion for 7 days, or give cytarabine as I.V. bolus followed by 5 days of cytarabine by continuous I.V. infusion. Second course may be given, depending on response. |
Mechanism of Action:
Inhibits nucleic acid synthesis by disrupting DNA and RNA polymerase, causing cell death.
Indications:
- Acute myeloid leukaemia
- Acute nonlymphocytic and chronic myelogenous leukaemia
- Non-Hodgkin’s lymphoma
- Breast cancer
Cautions & Contraindications:
- Hypersensitivity to drug
- Pregnancy or breastfeeding
Use cautiously in:
- Renal or hepatic impairment
- Bone marrow depression
- Previous treatment with anthracyclines or cardiotoxic drugs
- Cardiac disease.
Metabolism and Half- Life:
- Half-Life: 14-35 hr (PO); 12-27 hr (IV);
- Bioavailability: 30%
- Protein Bound: 94-97%
- Metabolism: Liver; Excretion: Urine (5-13%)
Drug Interactions:
Alkaline solutions, heparin: incompatibility
Side – Effects:
- CNS: headache, mental status changes, peripheral neuropathy, seizures
- CV: chest pain, heart failure, atrial fibrillation, myocardial infarction, arrhythmias
- GI: nausea, vomiting, diarrhoea, cramps, mucositis, GI haemorrhage
- GU: red urine, renal failure
- Hematologic: bone marrow depression
- Hepatic: hepatic function changes
- Metabolic: hyperuricemia
- Skin: alopecia, urticaria, bullous erythematous rash on palms and soles, erythema at previously irradiated site, tissue necrosis or urticaria at injection site
- Other: fever, infection, hypersensitivity reaction
Nursing Considerations
- Evaluate injection site for burning, stinging, and extravasation. If extravasation occurs, stop infusion and restart in another vein. Then rinse area with normal saline solution and apply cold compress. (Local infiltration with corticosteroids may be indicated.)
- Monitor patient’s response to therapy regularly.
- Assess serum uric acid level and CBC.
- Monitor hemodynamic status and cardiac output. Assess for S3 heart sound (which signals heart failure).
- Assess fluid intake and output. Make sure patient is adequately hydrated, to prevent hyperuricemia.
Patient/ Family Education:
- Instruct patient to immediately report unusual bleeding or bruising, difficulty breathing, or sudden weight gain.
- Tell patient to eat small, frequent meals. Advise patient to keep follow-up appointments for assessment, regular blood testing, and monitoring of drug effects
REFERENCES
- Robert Kizior, Keith Hodgson, Saunders Nursing Drug handbook,1st edition 2024, Elsevier Publications. ISBN-9780443116070
- McGraw Hill- Drug Handbook, Seventh Edition, 2013, McGraw Hill Education Publications,9780071799430.
- April Hazard, Cynthia Sanoski, Davi’s Drug Guide for Nurses -Sixteenth Edition 2019, FA Davis Company Publications,9780803669451.
- Jones and Bartlet, Pharmacology for Nurses, Second Edition, 2020, Jones and Bartlet Learning Publications, ISBN 9781284141986.
- Nursebro.com, Search – Nursebro
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