CeeNu


lomustine

CeeNU

Pharmacologic class: Alkylating drug (nitrosourea)

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Box Warning

• Give under supervision of physician experienced in cancer chemotherapy, in facility with adequate diagnostic and treatment resources. Most common and severe toxic effect is bone marrow suppression, which may contribute to bleeding and overwhelming infections in already compromised patients. Delayed bone marrow suppression is major toxicity, so monitor blood counts weekly for at least 6 weeks after dose. At recommended dosage, don't give courses more often than every 6 weeks. Bone marrow toxicity is cumulative; consider adjusting dosage based on nadir blood counts from previous dose.

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.

Availability

Capsules: 10 mg, 40 mg, 100 mg

Dose pack: two 10-mg capsules, two 40-mg capsules, and 100-mg capsules

Indications and dosages

Adjunctive therapy in primary and metastatic brain tumors; 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.

Dosage adjustment

• Bone marrow depression (based on WBC and platelet counts)

Contraindications

• Hypersensitivity to drug

Precautions

Use cautiously in:

• renal or hepatic dysfunction, bone marrow depression

• pregnant or breastfeeding patients.

Administration

• 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.

Adverse reactions

CNS: anxiety, confusion, dizziness, hallucinations, lethargy, headache, paresthesia, light-headedness, drowsiness, fatigue, seizures

GI: nausea; vomiting; anorexia; sore mouth, lips, and throat; GI bleeding

GU: amenorrhea, azoospermia, progressive azotemia, nephrotoxicity, renal failure

Hematologic: anemia, leukopenia, thrombocytopenia, bone marrow depression

Hepatic: hepatotoxicity

Skin: alopecia

Other: secondary cancers

Interactions

Drug-drug. Anticoagulants, non-steroidal anti-inflammatory drugs: increased bleeding risk

Myelosuppressants: increased bone marrow depression

Drug-diagnostic tests. Hemoglobin, platelets, red blood cells, WBCs: decreased values

Liver function tests, nitrogenous compounds: increased values

Patient monitoring

See Watch for evidence of overdose, including bone marrow depression, nausea, and vomiting.

See 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.

See Watch for signs and symptoms of secondary cancers.

Patient teaching

• Instruct patient to contact prescriber if he vomits shortly after taking drug.

See 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.

See 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.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

lomustine

(loe-mus-teen) lomustine,

CCNU

(trade name),

CeeNu

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: alkylating agents
Pregnancy Category: D

Indications

Used alone or with other agents for:
  • Primary and metastatic brain tumors,
  • Hodgkin’s disease.

Action

Inhibits DNA and RNA synthesis by alkylation (cell-cycle phase–nonspecific).

Therapeutic effects

Death of rapidly replicating cells, particularly malignant ones.

Pharmacokinetics

Absorption: Rapidly absorbed following oral administration.Distribution: Widely distributed. Active metabolites enter the CSF well. Enters breast milk.Metabolism and Excretion: Mostly metabolized by the liver. Some metabolites are active antineoplastic agents. Metabolites are excreted by the kidneys.Half-life: 1–2 days (active metabolites).

Time/action profile (effects on blood counts)

ROUTEONSETPEAKDURATION
POunknown4–7 wk1–2 wk

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Pregnancy or lactation.Use Cautiously in: Patients with childbearing potential; Active infections; Decreased bone marrow reserve (dosage reduction required); Geriatric patients or patients with other chronic debilitating illnesses; Impaired liver function.

Adverse Reactions/Side Effects

Central nervous system

  • ataxia
  • disorientation
  • dysarthria
  • lethargy

Respiratory

  • fibrosis
  • pulmonary infiltrates

Gastrointestinal

  • nausea (most frequent)
  • vomiting (most frequent)
  • anorexia
  • hepatotoxicity
  • stomatitis

Genitourinary

  • azotemia
  • renal failure

Dermatologic

  • alopecia

Endocrinologic

  • infertility

Hematologic

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

Metabolic

  • hyperuricemia

Miscellaneous

  • secondary malignancy (long-term use)

Interactions

Drug-Drug interaction

↑ bone marrow depression with other antineoplastics or radiation therapy.May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.

Route/Dosage

Oral (Adults and Children) 100–130 mg/m2 as a single dose every 6 wk (adjustments required for concurrent therapy or decreased blood counts).

Availability

Capsules: 10 mg, 40 mg, 100 mg

Nursing implications

Nursing assessment

  • Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and 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.
  • Assess for nausea and vomiting, which usually begin within 3 hr of administration and persist for 24 hr. Prophylactic antiemetics may be used. Monitor intake and output, daily weight, and appetite. Adjust diet as tolerated for anorexia.
  • Assess pulmonary function tests prior to initiation of therapy and periodically during therapy. Pulmonary toxicity may occur with cumulative doses of 600–1100 mg or with 6 mo or more of therapy.
  • Lab Test Considerations: Monitor CBC and differential prior to and periodically during therapy. The nadir of leukopenia occurs in 4–6 wk. The nadir of thrombocytopenia occurs in 4 wk. Notify physician if leukocyte count is <4000/mm3 or platelet count is <100,000/mm3. Recovery from leukopenia and thrombocytopenia occurs in 1–2 wk. Myelosuppression is cumulative; subsequent courses of therapy should be delayed until recovery occurs.
    • Monitor liver function studies (AST, ALT, LDH, bilirubin) and renal function studies (BUN, creatinine) prior to and periodically during therapy to detect hepatotoxicity and nephrotoxicity.
    • May cause ↑ uric acid. Monitor periodically during therapy.

Potential Nursing Diagnoses

Risk for infection (Side Effects)
Imbalanced nutrition: less than body requirements (Side Effects)

Implementation

  • Oral: Administer on empty stomach at bedtime. Preadministration of an antiemetic and a hypnotic may help control nausea.

Patient/Family Teaching

  • Instruct patient to take lomustine exactly as directed, even if nausea and vomiting occur. If vomiting occurs shortly after dose is taken, consult health care professional.
  • Inform patient that several different types of capsules may be found in medication container. Patient should take all the capsules at one time to receive the correct dose.
  • Advise patient to notify health care professional promptly if fever; chills; sore throat; signs of infection; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor. Caution patient not to drink alcoholic beverages or take products containing aspirin or other NSAIDs.
  • Instruct patient to notify health care professional if abdominal pain, yellow skin, weakness, cough, slurred speech, or decreased urine output occurs.
  • Instruct patient to inspect oral mucosa for redness and ulceration. If ulceration occurs, advise patient to use sponge brush and rinse mouth with water after eating and drinking. Consult health care professional if pain interferes with eating. Stomatitis pain may require treatment with opioid analgesics.
  • Discuss with patient the possibility of hair loss. Explore coping strategies.
  • Advise patient that, although lomustine may cause infertility, contraception is necessary because of potential teratogenic effects in the fetus.
  • Instruct patient not to receive any vaccinations without advice of health care professional.
  • Emphasize need for periodic lab tests to monitor for side effects.

Evaluation/Desired Outcomes

  • Decrease in size and spread of malignant tissue.