Name of the Alkylating Agents-Nitrosoureas Drugs
- Carmustine
- Lomustine
1.Carmustine
| CARMUSTINE |
| Availability : Injection, Powder for Reconstitution: 100 mg. Implant Device: (Gliadel Wafer): 7.7 mg. |
| May be carcinogenic, mutagenic, teratogenic. Wear protective gloves during preparation of drug; may cause transient burning, brown staining of skin |
| IV : Reconstitution • Reconstitute 100-mg vial with 3 mL sterile dehydrated (absolute) alcohol, followed by 27 mL Sterile Water for Injection to provide concentration of 3.3 mg/mL. • Further dilute with 50–250 mL D5W to final concentration of 0.2–1 mg/mL. Rate of administration • Infuse over 1–2 hrs (shorter duration may produce intense burning pain at injection site, intense flushing of skin, conjunctiva). Flush IV line with 5–10 mL 0.9% NaCl or D5W before and after administration to prevent irritation at injection site. Storage • Refrigerate unused vials. Reconstituted vials are stable for 8 hrs at room temperature or 24 hrs if refrigerated. Solutions further diluted with D5W are stable for 8 hrs at room temperature. Solutions appear clear, colourless to yellow. • Discard if precipitate forms, colour change occurs, or oily film develops on bottom of vial. (Gliadel Wafers): Store at or below −20°C (−4°F). Unopened pouches may be kept at room temperature for maximum of 6 hrs. |
| Know that drug may be used alone or in conjunction with other treatments, such as surgery or radiation. Follow facility policy when preparing, administering, and handling drug. Know that infusion lasting less than 1 hour causes intense pain and burning at I.V. site. Infuse solution in glass containers only; drug is unstable in plastic I.V. bags. Know that skin contact with reconstituted drug may cause transient hyperpigmentation. If contact occurs, wash skin thoroughly with soap and water. |
| Be aware that oxidized regenerated cellulose may be placed over wafers to secure them against surgical cavity surface. Know that resection cavity should be irrigated after wafer placement and that dura should be closed in watertight fashion. |
| Brain Tumours, Hodgkin’s Lymphoma, Non- Hodgkin’s Lymphoma, Multiple Myeloma: IV: (BiCNU): Adults, elderly: 150–200 mg/m2 as a single dose q6wks or 75–100mg/m2 on 2 successive days q6wks. Next dosage is based on clinical and hematologic response to previous dose (platelets greater than 100,000 cells/mm3 and leukocytes greater than 4,000 cells/mm3). |
| Glioblastoma Multiforme (Recurrent), Glioma (Malignant, Newly Diagnosed High-Grade) Implantation: (Gliadel Wafer): Adults, Elderly, children: Up to 8 wafers (62.6 mg) may be placed in resection cavity. |
| Adjunct to brain surgery: Adults: Up to 61.6 mg (eight wafers) implanted in surgical cavity created during brain tumour resection. |
| Dosage Modification: Leukocytes 2,000–2,999 cells/mm3 or platelets 25,000–74,999 cells/mm3: Give 70% of dose. Leukocytes less than 2,000 cells/mm3 or platelets less than 25,000 cells/mm3: Give 50% of dose. |
Mechanism of Action:
Inhibits DNA, RNA synthesis by crosslinking with DNA, RNA strands, preventing cell division. Cell cycle–phase nonspecific.
Therapeutic Effect: Interferes with DNA, RNA function.
Indications:
- Treatment of brain tumours
- Hodgkin’s lymphomas (relapsed/refractory)
- Non-Hodgkin’s lymphomas (relapsed/refractory)
- Multiple myeloma.
- Gliadel Wafer: Adjunct to surgery and radiation in treatment of newly diagnosed high-grade malignant glioma.
- Adjunct to surgery to prolong survival in recurrent glioblastoma multiforme.
OFF-LABEL:
- Treatment of mycosis fungoides (topical).
Cautions & Contraindications:
- Hypersensitivity to carmustine.
Cautions:
- Thrombocytopenia
- Leukopenia
- Anaemia
- Renal/hepatic impairment
Metabolism and Half- Life:
- Crosses blood-brain barrier.
- Metabolized in liver.
- Excreted in urine.
- Half-life: 15–30 min
Drug Interactions:
- Bone marrow depressants (e.g., cladribine) may enhance myelosuppressive effect.
- Live virus vaccines may potentiate virus replication, increase vaccine side effects, decrease pt’s antibody response to vaccine.
- May increase serum BUN, alkaline phosphatase, bilirubin, ALT, AST
Side- Effects:
- Frequent: Nausea, vomiting (may last up to 6 hrs).
- Occasional: Diarrhoea, esophagitis, anorexia, dysphagia, hyperpigmentation.
- Rare: Thrombophlebitis, burning sensation, pain at injection site.
Nursing Considerations
Baseline assessment
- Obtain CBC, renal/hepatic function studies before initiation and periodically thereafter.
- Offer emotional support
Intervention/evaluation
- Monitor renal/hepatic function tests.
- Obtain CBC weekly during and for at least 6 weeks after therapy ends.
- Monitor for hematologic toxicity (fever, sore throat, signs of local infection, unusual bruising/bleeding from any site), symptoms of anaemia (excessive fatigue, weakness).
- Monitor for pulmonary toxicity
- Observe for dyspnoea, adventitious breath sounds.
- Pulmonary function tests should be performed before therapy begins and regularly throughout therapy to assess for toxicity.
Patient/family teaching
- Maintain adequate hydration (may protect against renal impairment).
- Do not have immunizations without physician’s approval (drug lowers body’s resistance).
- Avoid contact with those who have recently received live virus vaccine.
- Report nausea, vomiting, fever, sore throat, chills, unusual bleeding/ bruising.
- Instruct patient to report signs and symptoms of allergic response and other adverse reactions.
- Inform patient that severe flushing may follow I.V. dose but should subside in 2 to 4 hours.
- Tell patient to avoid activities that can cause injury. Advise him to use soft toothbrush and electric razor to avoid gum and skin injury.
- Advise patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.
- Instruct patient to monitor urinary output and report significant changes.
- Inform patient that drug may cause hair loss.
- Advise patient that he’ll undergo regular blood testing during therapy.
2. Lomustine
| LOMUSTINE |
| Availability: Capsules: 10 mg, 40 mg, 100 mg ; Dose pack: two 10-mg capsules, two; 40-mg capsules, and 100-mg capsules |
| Administration and Handling: Obtain CBC with white cell differential before starting therapy. Administer antiemetic before giving drug, as prescribed, to minimize nausea. Give 2 to 4 hours after meals to enhance absorption. If vomiting occurs shortly after administration, notify prescriber. |
| Adjunctive therapy in primary and metastatic brain tumours; secondary therapy in Hodgkin’s disease Adults and children: As monotherapy, 130 mg/m2 P.O. as a single dose q 6 weeks in previously untreated patients. In bone marrow suppression, initial dosage is 100 mg/m2 P.O. q 6 weeks; don’t repeat dose until platelet count exceeds 100,000/mm3 and white blood cell (WBC) count exceeds 4,000/mm3.When given with other myelosuppressive drugs, adjust dosage accordingly. |
Mechanism of Action:
Inactivates neoplastic cells by alkylating DNA, causing DNA structural modification and fragmentation.
Thought to act in late G1 or early S phase of cell cycle.
Indications:
- Adjunctive therapy in primary and metastatic brain tumours
- Secondary therapy in Hodgkin’s disease
- Malignant gliomas
Off-label: pancreatic, liver, gastric, colorectal cancer; multiple myeloma; mycosis fungoides, psoriasis (topical)
Cautions & Contraindications:
- Hypersensitivity to drug
Use cautiously in:
- Renal or hepatic dysfunction, bone marrow depression
- Pregnant or breastfeeding patients.
Metabolism and Half- Life:
- Half-Life Elimination (biphasic): 16-24 hr (parent drug); 16-48 hr (active metabolite)
- Peak plasma time: ~3 hr;
- Metabolism: Liver
- Duration: 5-6 weeks (bone marrow recovery)
- Excretion: Urine (50%); faeces (<5%)
Drug interactions:
- Anticoagulants, nonsteroidal anti-inflammatory drugs: increased bleeding risk
- Myelo-suppressants: increased bone marrow depression
- Haemoglobin, platelets, red blood cells, WBCs: decreased values
- Liver function tests, nitrogenous compounds: increased values
Side- Effects:
- CNS: anxiety, confusion, dizziness, hallucinations, lethargy, headache, paraesthesia, light-headedness, drowsiness, fatigue, seizures
- GI: nausea; vomiting; anorexia; sore mouth, lips, and throat; GI bleeding
- GU: amenorrhea, azoospermia, progressive azotaemia, nephrotoxicity, renal failure
- Hematologic: anaemia, leukopenia, thrombocytopenia, bone marrow depression
- Hepatic: hepatotoxicity
- Skin: alopecia
- Other: secondary cancers
Nursing considerations
- Watch for evidence of overdose, including bone marrow depression, nausea, and vomiting.
- Monitor CBC and platelet counts closely.
- Watch for signs and symptoms of bleeding and bruising.
- Avoid I.M. injections if platelet count is below 100,000/mm3.
- Check kidney, liver, and pulmonary function tests frequently.
- Assess neurologic status carefully.
- Institute safety measures as needed to prevent injury.
- Watch for signs and symptoms of secondary cancers.
Patient/ Family Teaching:
- Instruct patient to contact prescriber if he vomits shortly after taking drug.
- Tell patient to immediately report easy bruising or bleeding, which may signal low platelet count.
- Advise patient to report changes in urination pattern.
- Instruct patient to avoid exposure to people with infections, because drug may make him more susceptible to infection.
- Caution female of childbearing age to use reliable contraception and to immediately report suspected or confirmed pregnancy.
- Advise female patient to inform prescriber if she is breastfeeding.
- Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
- Advise patient to minimize GI side effects by eating small, frequent servings of healthy food.
- Inform patient that drug may cause hair loss.
- Tell patient he’ll undergo frequent blood testing during therapy.
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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