Mutamycin


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Related to Mutamycin: mitomycin

mitomycin

Mutamycin

Pharmacologic class: Antitumor antibiotic

Therapeutic class: Antineoplastic

Pregnancy risk category C

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.

• Some patients receiving systemic drug have experienced hemolytic uremic syndrome, a serious complication consisting primarily of microangiopathic hemolytic anemia, thrombocytopenia, and irreversible renal failure. Syndrome may arise at any time during systemic therapy, but most cases occur at doses of 60 mg or higher. Blood product transfusion may exacerbate symptoms.

Action

Selectively inhibits DNA synthesis by causing cross-linking of DNA strands and suppressing RNA and protein synthesis, resulting in cell death

Availability

Injection: 5-mg, 20-mg, and 40-mg vials

Indications and dosages

Disseminated adenocarcinoma of stomach or pancreas (given with other chemotherapeutic agents); palliative treatment when other therapies fail

Adults: 20 mg/m2 I.V. as a single dose. Repeat cycle q 6 to 8 weeks, adjusting dosage if necessary.

Dosage adjustment

• Reduced white blood cell or platelet count

Contraindications

• Hypersensitivity to drug
• Thrombocytopenia, coagulation disorders, increased bleeding tendency

Precautions

Use cautiously in:
• active infections, decreased bone marrow reserve, impaired hepatic function
• history of pulmonary disorders
• elderly patients
• pregnant or breastfeeding patients.

Administration

Follow facility policy for handling, administering, and disposing of mutagenic, teratogenic, and carcinogenic drugs.
• Reconstitute 5-mg vial with 10 ml of sterile water. Shake, let mixture stand, and administer by direct I.V. injection through Y-tube or three-way stopcock. Infuse over 5 to 10 minutes through line with running infusion of normal saline solution or dextrose 5% in water.

Avoid extravasation and contact with skin, mucous membranes, and eyes.

Adverse reactions

GI: nausea, vomiting, anorexia, mouth ulcers, stomatitis

GU: renal failure, hemolytic uremic syndrome

Hematologic: anemia, leukopenia, thrombocytopenia

Respiratory: pulmonary toxicity, interstitial pneumonitis

Skin: reversible alopecia; pruritus; desquamation; phlebitis, necrosis, and sloughing with I.V. site extravasation

Other: fever

Interactions

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

Other antineoplastics: additive bone marrow depression

Vinca alkaloids: respiratory toxicity

Patient monitoring

Closely monitor CBC with white cell differential and platelet count. Stay alert for evidence of blood dyscrasias.
• Assess kidney function tests. Measure fluid intake and output and evaluate fluid balance.

Watch for signs and symptoms of hemolytic uremic syndrome (irritability, fatigue, pallor, and decreased urinary output).

Closely monitor I.V. site and skin integrity to prevent extravasation.

Assess respiratory status carefully to detect severe pulmonary problems.

Patient teaching

Teach patient to recognize and immediately report signs and symptoms of hemolytic uremic syndrome, blood dyscrasias, and renal failure.

Instruct patient to report cough or shortness of breath, even if it occurs several months after therapy ends.
• Advise patient to limit exposure to infections and to avoid live vaccines.
• Tell patient drug may cause hair loss. Discuss options for dealing with this problem.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs mentioned above.

mitoMYcin

(mye-toe-mye-sin) ,

Mutamycin

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: antitumor antibiotics
Pregnancy Category: D

Indications

Used with other agents in the management of disseminated adenocarcinoma of the stomach or pancreas.Palliative treatment of:
  • Carcinoma of the colon or breast,
  • Head and neck tumors,
  • Advanced biliary, lung, and cervical squamous cell carcinomas.

Action

Primarily inhibits DNA synthesis by causing cross-linking; also inhibits RNA and protein synthesis (cell-cycle phase–nonspecific but is most active in S and G phases).

Therapeutic effects

Death of rapidly replicating cells, particularly malignant ones.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Widely distributed, concentrates in tumor tissue. Does not enter CSF.
Metabolism and Excretion: Mostly metabolized by the liver. Small amounts (<10%) excreted unchanged by the kidneys and in bile.
Half-life: 50 min.

Time/action profile (effects on blood counts)

ROUTEONSETPEAKDURATION
IV3–8 wk4–8 wkup to 3 mo

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Pregnancy or lactation.
Use Cautiously in: Active infections;↓ bone marrow reserve;Hepatic dysfunction;History of pulmonary problems; Obstetric: Patients with childbearing potential should be counseled to avoid pregnancy during treatment; Geriatric: May have ↑ sensitivity to drug effects.

Adverse Reactions/Side Effects

Respiratory

  • pulmonary toxicity (life-threatening)

Cardiovascular

  • edema

Gastrointestinal

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

Genitourinary

  • infertility
  • renal failure

Dermatologic

  • alopecia
  • desquamation

Hematologic

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

Local

  • phlebitis at IV site (most frequent)

Miscellaneous

  • hemolytic uremic syndrome (life-threatening)
  • fever
  • prolonged malaise

Interactions

Drug-Drug interaction

Additive bone marrow depression with other antineoplastics or radiation therapy.May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.Concurrent or sequential use with vinca alkaloids may result in respiratory toxicity.

Route/Dosage

Intravenous (Adults) 20 mg/m2 every 6–8 wk.

Availability (generic available)

Powder for injection: 5 mg/vial, 20 mg/vial, 40 mg/vial

Nursing implications

Nursing assessment

  • Monitor vital signs periodically during administration.
  • 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, appetite, and nutritional intake. Nausea and vomiting usually occur within 1–2 hr. Vomiting may stop within 3–4 hr; nausea may persist for 2–3 days. Antiemetics may be administered prophylactically. Adjust diet as tolerated to help maintain fluid and electrolyte balance and nutritional status.
  • Assess respiratory status and chest x-ray examination prior to and periodically throughout course of therapy. Cough, bronchospasm, hemoptysis, or dyspnea usually occurs after several doses and may be indicative of pulmonary toxicity, which may be life threatening.
  • Monitor for potentially fatal hemolytic uremic syndrome in patients receiving long-term therapy. Symptoms include microangiopathic hemolytic anemia, thrombocytopenia, renal failure, and hypertension.
  • Lab Test Considerations: Monitor CBC with differential, platelet count, and observation for fragmented RBCs on peripheral blood smears prior to and periodically throughout therapy and for several months following therapy.
    • The nadirs of leukopenia and thrombocytopenia occur in 4–8 wk. Notify health care professional if leukocyte count is <4000/mm3 or if platelet count is <150,000/mm3 or is progressively declining. Recovery from leukopenia and thrombocytopenia occurs within 10 wk after cessation of therapy. Myelosuppression is cumulative and may be irreversible. Repeat courses of therapy are held until leukocyte count is >4000/mm3 and platelet count is >100,000/mm3.
    • Monitor liver function studies (AST, ALT, LDH, bilirubin) and renal function studies (BUN, creatinine) prior to and periodically throughout therapy to detect hepatotoxicity and nephrotoxicity. Notify health care professional if creatinine is >1.7 m g/dL.

Potential Nursing Diagnoses

Risk for injury (Side Effects)
Risk for infection (Side Effects)
Disturbed body image (Side Effects)

Implementation

  • Do not confuse mitomycin with mitoxantrone.
  • Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in designated containers.
    • Ensure patency of IV. Extravasation may cause severe tissue necrosis. If patient complains of discomfort at IV site, discontinue immediately and restart infusion at another site. Promptly notify physician of extravasation.
  • Intravenous Administration
  • pH: 6.0–8.0.
  • Reconstitute 5-mg vial with 10 mL and 10-mg vial with 40 mL of sterile water for injection. Shake the vial; may need to stand at room temperature for additional time to dissolve. Final solution is blue-gray. Reconstituted solution is stable for 7 days at room temperature, 14 days if refrigerated. Diluent: 0.9% NaCl.Concentration: 20–40 mcg/mL for administration.
  • Rate: May be administered IV push over 5–10 min through free-flowing IV of 0.9% NaCl or D5W.
  • Y-Site Compatibility: amifostine, amphotericin B lipid complex, amphotericin B liposome, anidulafungin, argatroban, bivalirudin, bleomycin, caspofungin, cisplatin, cyclophosphamide, doxorubicin, cyclophosphamide, dactinomycin, dexmedetomidine, doxorubicin hydrochloride, droperidol, epirubicin, ertapenem, fluorouracil, furosemide, granisetron, heparin, leucovorin calcium, levofloxacin, melphalan, meperidine, methotrexate, metoclopramide, nesiritide, octreotide, ondansetron, ondansetron, teniposide, thiotepa, tigecycline, tirofiban, trastuzamab, vinblastine, vincristine, voriconazole, zoledronic acid
  • Y-Site Incompatibility: aztreonam, cefepime, daptomycin, etoposide phosphate, fenoldopam, filgrastim, gemcitabine, pantoprazole, piperacillin/tazobactam, sargramostim, topotecan, vinorelbine

Patient/Family Teaching

  • Instruct patient to notify health care professional promptly if fever; chills; cough; hoarseness; sore throat; signs of infection; lower back or side pain; painful or difficult urination; 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; may precipitate gastric bleeding.
  • Instruct patient to notify health care professional if decreased urine output, edema in lower extremities, shortness of breath, skin ulceration, or persistent nausea 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. Topical agents may be used if pain interferes with eating. Stomatitis pain may require treatment with opioid analgesics.
  • Discuss with patient the possibility of hair loss. Explore coping strategies.
  • Instruct patient not to receive any vaccinations without advice of health care professional.
  • Advise patient that, although mitomycin may cause infertility, contraception during therapy is necessary because of teratogenic effects.
  • Emphasize need for periodic lab tests to monitor for side effects.

Evaluation/Desired Outcomes

  • Decrease in size and spread of malignant tissue.

Mutamycin

a trademark for an antineoplastic (mitomycin).