Name of the Alkylating Drugs
- Busulfan
- Procarbazine
1. Busulphan
| BUSULPHAN |
| Availability: Injection: 6 mg/ml in 10-ml ampules; Tablets: 2 mg |
| Administration and Handling: Give oral doses on empty stomach. When administering I.V., withdraw dose from ampule using 5-micron filter needle. Remove filter needle and use new needle to add busulfan to diluent. Dilute for injection using dextrose 5% in water or normal saline solution. Infuse I.V. dose over 2 hours, using an infusion pump. Flush I.V. catheter before and after each infusion with 5 ml D5W or normal saline solution. Be aware that drug is highly toxic and has a narrow therapeutic index. Maintain vigorous hydration to reduce risk of renal toxicity. Handle patient gently to avoid bruising. |
| IV Preparation: Dilute and administer as intravenous infusion; do not administer as intravenous push or bolus Do not infuse other medications simultaneously. Dilute busulfan injection in NS or D5W; do not use other diluents Dilution volume should be 10x volume of busulfan concentrate, ensuring final concentration is equal to or >0.5 mg/mL IV Administration: Administer via a central venous catheter as a 2 hr infusion, q6hr for 4 consecutive days for a total of 16 doses. Do not use polycarbonate syringes Storage : Store unopened ampules (injection) under refrigeration at 2-8°C; Prolonged storage (>8 hr) in D5W or NS at room temp causes 10%+ loss of potency |
| Chronic myelogenous leukemia : Adults: 4 to 8 mg P.O. daily until white blood cell (WBC) count decreases to 15,000/mm3; then discontinue drug until WBC count rises to 50,000/mm3 and then resume as needed. Children: 0.06 to 0.12 mg/kg/day P.O. or 1.8 to 4.6 mg/m2/day P.O. Adjust dosage to maintain WBC count at approximately 20,000/mm3. Drug should be withheld when WBC count decreases to approximately 15,000/mm3. |
| Allogenic hematopoietic stem cell transplantation : Adults: 0.8 mg/kg I.V. q 6 hours for 4 days. Starting 6 hours after 16th dose of busulfan injection, give cyclophosphamide 60 mg/kg/day I.V. over 1 hour for 2 days. |
Mechanism of Action:
Interfere with bacterial cell-wall synthesis by cross-linking strands of DNA and disrupting RNA transcription, which causes cell to rupture and die. Exhibits minimal immunosuppressant activity.
Indications:
- Chronic myelogenous leukaemia
- Allogenic hematopoietic stem cell transplantation
- Adjunctive therapy in ovarian cancer
- Bone marrow transplantation
Cautions & Contraindications:
- Hypersensitivity to drug
- Patients not definitively diagnosed with chronic myelogenous leukaemia
- Pregnancy or breastfeeding
Use cautiously in:
- Active infections, decreased bone marrow reserve, chronic debilitating disease, depressed neutrophil and platelet counts, seizure disorders, obesity
- Patients receiving concurrent myelosuppressive or radiation therapy
- Females of childbearing age
Metabolism and Half- Life:
- Onset: 1-2 weeks.
- Duration: 24 hr
- Time to peak serum: 1hr (PO); 5 min (IV)
- Protein bound: 32% Metabolized in Liver
- Half-life elimination: 2.5 hr; Excretion: Urine (25-60%)
Drug Interactions:
- Anticoagulants, aspirin, nonsteroidal anti-inflammatory drugs: increased risk of bleeding
- Live-virus vaccines: decreased antibody response to vaccine, increased risk of adverse reactions
- Myelo- suppressants: additive bone marrow depression
- Nephrotoxic and ototoxic drugs (such as aminoglycosides, loop diuretics): additive nephrotoxicity and ototoxicity
- Thioguanine: increased risk of hepatotoxicity
- Alkaline phosphatase, aspartate aminotransferase, bilirubin, nitrogenous compounds (urea): increased levels
- Haemoglobin, WBCs: decreased values
Side – Effects:
- CNS: anxiety, confusion, depression, dizziness, headache, insomnia, weakness, encephalopathy, seizures, cerebral haemorrhage, coma
- CV: chest pain, hypotension, hypertension, tachycardia, ECG changes, heart block, left-sided heart failure, thrombosis, pericardial effusion, ventricular extrasystole, atrial fibrillation, arrhythmias, cardiac tamponade, cardiomegaly
- EENT: cataracts, ear disorders, epistaxis, pharyngitis
- GI: nausea, vomiting, diarrhoea, constipation, abdominal pain, dyspepsia, abdominal enlargement, pancreatitis, hematemesis, dry mouth, stomatitis, anorexia
- GU: dysuria, haematuria, sterility, gynecomastia, oliguria
- Hematologic: febrile neutropenia, thrombotic microangiopathy, profound myelosuppression
- Hepatic: hepatitis, hepatomegaly
- Metabolic: hypokalaemia, hypomagnesemia, hypophosphatemia, hyperuricemia, hyperglycaemia
- Musculoskeletal: arthralgia, myalgia, back pain
- Respiratory: hyperventilation, dyspnoea, pulmonary fibrosis
- Skin: pruritus, rash, acne, alopecia, erythema nodosum, exfoliative dermatitis, hyperpigmentation
- Other: allergic reactions, chills, fever, injection site infection or inflammation; severe bacterial, viral, fungal infections; sepsis; tumour lysis syndrome
Nursing Considerations
- Monitor patient closely for adequate hydration.
- Check for signs and symptoms of local or systemic infections.
- Assess for bleeding and excessive bruising.
- Evaluate oral hygiene regularly.
- Monitor CBC and WBC and platelet counts daily if patient is receiving I.V. busulfan.
- Monitor renal and hepatic function.
- Know that diffuse pulmonary fibrosis (“busulfan lung”) is a rare but potentially life-threatening complication, with symptom onset as late as 10 years after therapy.
Patient/ Family Teaching:
- Inform patient that drug doesn’t cure leukaemia but may induce remission.
- Advise patient to drink plenty of fluids to avoid dehydration.
- Instruct patient to immediately report inability to eat or drink. Prescriber may add another drug to improve appetite.
- Inform patient that he’s at increased risk for infection. Advise him to avoid contact with people with known infections and to avoid public transportation, if possible.
- Tell patient he’s at increased risk for bleeding and bruising.
- Advise patient to avoid activities that can cause injury and to use soft toothbrush and electric razor to avoid gum and skin injury.
- Inform patient that he’ll undergo frequent blood testing to monitor drug effects
2.Procarbazine
| PROCARBAZINE |
| Availability: Capsules: 50 mg |
| Administration and Handling: Weigh patient; know that dosages are based on weight. However, use caution in patients with Edema or ascites. Do not chew or crush the capsules before swallowing |
| Hodgkin’s disease: Adults: 2 to 4 mg/kg P.O. daily as a single dose or in divided doses for 1 week, then 4 to 6 mg/kg P.O. daily until white blood cell (WBC) count is less than 4,000/mm3 or platelet count is less than 100,000/mm3, or until desired response occurs. With desired response, give maintenance dosage of 1 to 2 mg/ kg P.O. daily (rounded off to nearest 50 mg). As component of MOPP (mechlorethamine, vincristine, procarbazine, prednisone) regimen for advanced Hodgkin’s disease, usual dosage is 100 mg/m2 P.O. daily on days 1 to 14 of 28-day cycle. Children: Dosage highly individualized. Usual dosage is 50 mg/m2 P.O. daily for first week, then 100 mg/m2 P.O. daily until leukopenia, thrombocytopenia, or desired response occurs. With desired response, maintenance dosage is 50 mg/m2 P.O. daily |
Mechanism of Action:
Thought to inhibit DNA, RNA, and protein synthesis, resulting in death of rapidly dividing cells. Also inhibits MAO.
Indications:
- Hodgkin’s disease
OFF- LABEL:
- Brain tumour
- Lymphoma
Cautions & Contraindications:
- Hypersensitivity to drug
- Inadequate bone marrow reserve
Use cautiously in:
- Infection, chronic debilitating illness, headache, hepatic or renal impairment, cardiovascular disease, heart failure, diarrhoea, stomatitis, pheochromocytoma, psychiatric illness, alcoholism
- Patients who have undergone radiation therapy or received other chemotherapy drugs within previous month
- Elderly patients
- Pregnant or breastfeeding patients
- Females of childbearing age.
Metabolism and Half- Life:
- Half-life elimination: 1 hr;
- Peak plasma time: 1 hr
- Metabolism: liver, kidney
- Excretion: Urine
Drug Interactions:
- Digoxin: decreased digoxin blood level
- Levodopa: flushing, hypertension
- Opioids: deep coma, death
- Sympathomimetics (indirect acting): abrupt, life-threatening hypertension
- Tricyclic antidepressants: severe toxicity and fatal reactions (including blood pressure fluctuations, seizures, and coma)
- Haematocrit, haemoglobin, platelets, reticulocytes, WBCs: decreased levels
- Caffeine-containing foods and beverages: hypertension, arrhythmias
- Tyramine-containing foods and beverages: life-threatening hypertension
- Alcohol use: disulfiram- like reaction
Side- Effects:
- CNS: confusion, dizziness, drowsiness, hallucinations, headache, mania, depression, nightmares, psychosis, syncope, tremor, neuropathy, paraesthesia, seizures
- CV: Edema, hypotension, tachycardia
- EENT: nystagmus, photophobia, retinal haemorrhage
- GI: nausea, vomiting, diarrhoea, dysphagia, ascites, stomatitis, dry mouth, anorexia
- GU: gonadal suppression, gynecomastia
- Hematologic: anaemia, leukopenia, thrombocytopenia
- Hepatic: hepatic dysfunction
- Respiratory: cough, pleural effusion
- Skin: alopecia, photosensitivity, pruritus, rash
Nursing Considerations
- Monitor vital signs and nutritional status.
- Assess fluid intake and output. Watch for evidence of fluid overload.
- Monitor neurologic status for seizures, paraesthesia, neuropathy, and confusion. Discontinue drug and notify prescriber if these occur.
- Monitor CBC and platelet count. Discontinue drug and contact prescriber if WBC count falls below 4,000/mm3 or platelet count falls below 100,000/mm3.
- Evaluate patient’s concurrent drug use to ensure that he isn’t receiving other drugs that could cause potentially fatal interactions.
- Check for diarrhoea. Discontinue drug and contact prescriber if patient has frequent bowel movements or watery stools.
- Monitor blood urea nitrogen level, liver and kidney function tests, and urinalysis.
- Discontinue drug at first sign of hypersensitivity, stomatitis, diarrhoea, or bleeding.
Patient/ Family Teaching:
- Instruct patient to avoid caffeine containing foods and beverages.
- Tell patient to avoid foods and beverages containing tyramine (such as cheese, Chianti wine, tea, coffee, cola, and bananas).
- Advise patient to avoid alcohol.
- Tell female of childbearing age to discuss contraception with prescriber.
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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