Medication Guide App

Mitomycin

Class: Antineoplastic Agents
VA Class: AN200
Molecular Formula: C15H18N4O5
CAS Number: 50-07-7
Brands: Mutamycin

Warning(s)

  • Experience of Supervising Clinician
  • Administer only under the supervision of a qualified clinician experienced in therapy with chemotherapeutic agents.100 d Use only when adequate treatment facilities for appropriate management of therapy and complications are available.100 d (See Toxicity under Cautions.)

  • Myelosuppression
  • Risk of dose-limiting, cumulative myelosuppression and potentially life-threatening secondary infections (e.g., septicemia).100 c d (See Hematologic Effects under Cautions.)

  • Hemolytic Uremic Syndrome
  • Undefined risk of severe and often fatal syndrome consisting principally of microangiopathic hemolytic anemia (hematocrit ≤25%), thrombocytopenia (platelet count ≤100,000/mm3), and irreversible renal failure (Scr ≥1.6 mg/dL).100 101 102 103 104 105 106 107 108 d (See Hemolytic Uremic Syndrome under Cautions.)

  • May occur at any time during therapy (with or without other antineoplastic agents); however, most cases occur at mitomycin doses ≥60 mg.100 d Blood transfusion may exacerbate the symptoms associated with this syndrome.100 d

Introduction

Antineoplastic agent; an antibiotic produced by Streptomyces caespitosus.100 c d

Uses for Mitomycin

Adenocarcinoma of Stomach and Pancreas

Component of combination chemotherapeutic regimens for treatment of disseminated adenocarcinoma of the stomach or pancreas and as palliative treatment of these tumors when other treatment modalities are ineffective.100 121 d

Response rates generally low (10–17%) and of short duration.c

Not recommended for use as single-agent, primary therapy or as a replacement for appropriate surgery and/or radiation therapy.100 d

Anal Cancer

A preferred regimen, in combination with fluorouracil, for primary treatment of anal cancer.121

Bladder Cancer

Has been used for intravesical treatment of residual tumor and/or as adjuvant therapy for prophylaxis of superficial bladder cancer.113 115 120 121 130 131 138

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Causes regression of existing papillary tumor and reduces the rate of short-term tumor recurrence but has no effect on disease progression or overall survival.119 123 124 129 139

Cervical Cancer

Has been used in cisplatin-containing combination chemotherapy regimens (e.g., bleomycin, cisplatin, mitomycin, and vincristine) for treatment of metastatic or recurrent cervical cancer.132 135

Other agents generally preferred for treatment of advanced cervical cancer.136 137

Non-small Cell Lung Cancer

Has been used for treatment of non-small cell lung cancer in combination with cisplatin and vinblastine (MVP) 121 146 149 or ifosfamide with mesna (MIC).121 150

Other chemotherapeutic regimens (e.g., cisplatin with paclitaxel, vinorelbine, or gemcitabine) currently preferred for treatment of advanced non-small cell lung cancer.121 146

Malignant Mesothelioma

Has been used for treatment of malignant mesothelioma.121

Head and Neck Carcinoma

Has been used as an adjunct to radiation therapy for treatment of squamous cell carcinoma of head and neck.147

Breast Cancer

Has shown activity for treatment of metastatic breast cancer.148

Mitomycin Dosage and Administration

General

  • Consult specialized references for procedures for proper handling and disposal of antineoplastic drugs.100 d

  • Administer mitomycin only after complete hematologic recovery from any previous chemotherapy occurs.100

Administration

Administer IV.100 c d

Has been administered intravesically; notan approved route of administration.100 115 120 121 130 131 138 d

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer via a functioning IV catheter;100 c d some clinicians recommend administering the drug through tubing of an IV infusion.c Use care to avoid extravasation.100 d (See Mucocutaneous Effects under Cautions.)

Reconstitution

Reconstitute vial containing 5, 20, or 40 mg of mitomycin with 10, 40, or 80 mL of sterile water for injection, respectively, to provide a solution containing approximately 0.5 mg/mL.100 c d

Shake vial to dissolve.100 c d If the powder does not dissolve immediately, allow the vial to stand at room temperature until complete dissolution occurs.100 c d

Dosage

Consult published protocols for dosages of mitomycin and other chemotherapeutic agents and the method and sequence of administration.c

Individualize dosage based on clinical and hematologic response and tolerance of the patient and whether or not other myelosuppressive therapy also is being used.100 c d

Reevaluate patients after each course of therapy and adjust dosages as needed.100 d

Adults

Adenocarcinoma of Stomach and Pancreas
IV

Initially, 20 mg/m2 as a single IV dose every 6–8 weeks.100 d Doses >20 mg/m2 are not more effective and increase risk of toxicity.100 d

Adjust subsequent dosages according to the hematologic response to the previous dose.100 d (See Table 1.)Do not administer repeat dosage until leukocyte count has returned to 4000/mm3 and platelet count to 100,000/mm3.100 d

Table 1: Dosage Modification for Myelosuppression Based on Nadir After Prior Dose100d

Leukocytes (cells/ mm3)

Platelets (cells/ mm3)

Percentage of Prior Dose to Be Given

>4000

>100,000

100%

3000–3999

75,000–99,999

100%

2000–2999

25,000–74,999

70%

<2000

<25,000

50%

If disease continues to progress after 2 courses of therapy, discontinue the drug since likelihood of response is minimal.100 d

Bladder Cancer
Treatment of Superficial Bladder Cancer
Intravesical

Usual dosage: 20–60 mg once weekly,115 116 118 120 125 126 127 128 administered as soon as possible following transurethral resection (TUR).117 128 For patients treated within 6–24 hours following TUR, a 6-month course of therapy generally is sufficient; however, for patients in whom intravesical therapy is instituted ≥24 hours following surgery, a 12-month course usually is recommended.117 128 No additional benefit demonstrated for continued maintenance therapy.115 116 120 124 128 131

Special Populations

Hepatic Impairment

No special dosage recommendations at this time.100 d

Renal Impairment

Do not administer if Scr >1.7 mg/dL.100 d (See Renal Effects under Cautions.)

Geriatric Patients

No special dosage recommendations at this time.100 d

Cautions for Mitomycin

Contraindications

  • Thrombocytopenia, coagulation disorder, or an increase in bleeding tendency due to other causes.100 c d (See Hematologic Effects under Cautions.)

  • Known hypersensitivity or idiosyncratic reaction to mitomycin.100 c d

Warnings/Precautions

Warnings

Toxicity

Highly toxic drug with a low therapeutic index.c Administer only under the supervision of a qualified clinician experienced in use of cancer chemotherapeutic agents.100 c d (See Boxed Warning and also see Hematologic Effects, Renal Effects, Hemolytic Uremic Syndrome, and Respiratory Effects under Cautions.)

Hematologic Effects

High incidence of cumulative myelosuppression, principally thrombocytopenia and leukopenia.100 c d (See Boxed Warning.) Not related to total dose; however, occurs more frequently with certain dosage regimens.c

Monitor hematologic status (platelet count, leukocyte count, differential, PT, bleeding time, and hemoglobin) repeatedly during therapy and for ≥8 weeks afterwards.100 c d Withhold therapy if leukocyte count <4000/mm3, platelet count <100,000/mm3, or if a progressive decline in either occurs.100 d (See Table 1.)

Myelosuppression may occur anytime within 8 weeks after initiation of therapy; may be severe (e.g., platelet count ≤50,000/mm3, leukocyte count ≤2000/mm3).100 c d Nadir during 4–6 weeks of therapy.c Recovery usually occurs ≤10 weeks after therapy discontinued; however, about 25% of cases may be irreversible.100 d

Hemorrhagic Complications

Bleeding due to thrombocytopenia may occur.c Platelet transfusions may be needed.c

Infectious Complications

Life-threatening infections secondary to leukopenia (e.g., septicemia) reported.100 c d

Renal Effects

Renal toxicity (e.g., increased BUN and/or Scr) reported.100 c d Possibly related to total dose administered (e.g., low risk at cumulative doses <50 mg/m2; substantially increases with higher cumulative doses);101 108 however, not clearly established.100 d

Monitor renal function.100 Do not administer if Scr >1.7 mg/dL.100 d

Renal failure also may occur as a component of hemolytic uremic syndrome.100 101 102 103 104 105 106 107 108 (See Hemolytic Uremic Syndrome under Cautions and also see Boxed Warning.)

Fetal/Neonatal Morbidity

May cause fetal harm; teratogenicity demonstrated in animals.100 d

Safe use of mitomycin in pregnant women not established.100 d

Major Toxicities

Hemolytic Uremic Syndrome

Hemolytic uremic syndrome, a severe and often fatal syndrome of microangiopathic hemolytic anemia (hematocrit ≤25%), thrombocytopenia (platelet count ≤100,000/mm3), and irreversible renal failure (Scr ≥1.6 mg/dL), reported.100 101 102 103 104 105 106 107 108 d Pulmonary edema also may be a component; may be a particularly grave prognostic factor.100 104 d Other complications include neurologic abnormalities and hypertension.100 d (See Boxed Warning.)

Syndrome can vary from a chronic course with mild anemia and slowly progressive renal impairment to a fulminant course with severe anemia, rapid deterioration of renal function, and death.101 102 103 104 105 106 107 108

May occur at any time during therapy (with or without other antineoplastic agents); however, most cases occur at doses ≥60 mg.100 d Blood transfusion may exacerbate symptoms.100 d

Closely monitor patients receiving mitomycin doses ≥60 mg for unexplained anemia with fragmented cells on peripheral blood smear, thrombocytopenia, and decreased renal function.100 d

Optimum management of syndrome not established; use of systemic corticosteroids, plasma exchange, plasmapheresis, and/or IV vincristine beneficial in some patients, and early treatment may be preferred.103 104 105 106 107 108 (See Specific Drugs under Interactions.) Manufacturer states that therapy for syndrome is investigational.100 d

General Precautions

Mucocutaneous Effects

Extremely irritating to tissues.c Mucocutaneous toxicity (e.g., mouth ulcers, alopecia, desquamation, pruritus) may occur; appears related to the total dose given.c d

Extravasation possible; may cause severe cellulitis, ulceration, and tissue sloughing.100 d May occur with or without symptoms (e.g., stinging or burning during administration) and even when blood returns well during initial aspiration of infusion needle.100 d (See IV Administration under Dosage and Administration.)

Possible pain on injection, induration, thrombophlebitis, and paresthesia.c Delayed erythema and/or ulceration at or distant from the injection site possible weeks to months after administration despite the lack of apparent evidence of extravasation.100 d

Respiratory Effects

Possibly severe or life-threatening acute bronchospasm and/or dyspnea may occur a few minutes to several hours after administration of a vinca alkaloid (e.g., vinblastine) in patients who have been previously or simultaneously treated with mitomycin.100 c d Bronchodilators, corticosteroids, and/or oxygen may produce symptomatic relief.100 d

ARDS reported in some patients receiving mitomycin in combination with other antineoplastic agents and maintained at fraction of inspired oxygen (FIO2) concentrations >50% perioperatively.100 d Use only enough oxygen to provide adequate arterial saturation.100 d

Monitor patients for evidence of pulmonary toxicity (e.g., dyspnea with a nonproductive cough, radiographic evidence of pulmonary infiltrates) and for changes in fluid balance; avoid overhydration.100 d If pulmonary toxicity develops, discontinue therapy if other etiologies can be excluded.100 d

Intravesical Instillation

Bladder fibrosis/contraction reported;100 d may require cystectomy.100 d

Asymptomatic ulcers at the site of resected carcinoma of the bladder109 110 111 and calcification of bladder wall reported.112

Possible local irritation (i.e., cystitis); local toxicity increases with the number and frequency of instillations and with the dose administered.115

GI Effects

Nausea and vomiting may occur within 1–2 hours of IV administration.100 c d Vomiting usually subsides rapidly but nausea can continue for 2–3 days.c

Specific Populations

Pregnancy

Category C.100 d (See Fetal/Neonatal Morbidity under Cautions.)

Lactation

Not known whether mitomycin is distributed into milk.100 d Discontinue nursing during mitomycin therapy.100 d

Pediatric Use

Safety and efficacy not established.100 d

Renal Impairment

Do not use if Scr >1.7 mg/dL.100 d Monitor renal function prior to and periodically during therapy.100 d (See Renal Effects under Cautions.)

Common Adverse Effects

IV administration: Myelosuppression, nausea, vomiting, anorexia, stomatitis, fever, alopecia.100 d

Intravesical instillation: Local irritation (i.e., cystitis).115

Interactions for Mitomycin

Specific Drugs

Drug

Interaction

Comments

Antineoplastic agents

Risk of acute pulmonary reactions following administration of vinca alkaloids (e.g., vinblastine, vincristine, vinorelbine) in patients previously or concomitantly treated with mitomycin100 d (see Respiratory Effects under Cautions)

Risk of ARDS in patients receiving mitomycin in combination with other chemotherapeutic agents and oxygen therapy100 c d (see Respiratory Effects under Cautions)

Bronchodilators, corticosteroids, and/or oxygen may produce symptomatic relief from acute bronchospasm and/or dyspnea100 d

Use only enough oxygen to provide adequate arterial saturation during ARDS100 d

Myelosuppressive agents

Adjust dosages accordingly when used concomitantly100 d

Mitomycin Pharmacokinetics

Distribution

Extent

Rapidly distributed into tissues.c

In animals, highest concentrations found in the kidneys, followed by muscles, eyes, lungs, intestines, and stomach; not detectable in the liver, spleen, or brain (rapidly inactivate mitomycin).c

Higher concentrations of the drug are generally present in cancer tissues than in normal tissues.c

Not known whether mitomycin is distributed into milk.100 d

Elimination

Metabolism

Rapidly inactivated in microsomal fraction of the liver and also in the kidneys, spleen, brain, and heart, which contain high concentrations of enzymes capable of metabolizing the drug.100 c

Elimination Route

Excreted principally in urine (about 10% as active drug) and to a small extent in bile.100 c d

Rate of clearance inversely proportional to the maximum serum concentration because of saturation of degradative pathways.100 d

Half-life

For 30-mg IV injection: 17 minutes.100 d

Stability

Storage

Parenteral

Powder for Injection

15–30°C.c d Protect from lightc and avoid excessive heat (>40°C).100 c d Commercially available mitomycin powder is stable for at least 4 years at room temperature.c

Reconstituted solutions are stable for 7 days at room temperature and for 14 days at 2–8°C.100 c d Protect from light.d

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility100 HID

Solutions of mitomycin diluted to a concentration of 20–40 mcg/mL are stable at room temperature for 3 hours in 5% dextrose injection, 12 hours in 0.9% sodium chloride, and 24 hours in sodium lactate injection.100 c d

Compatible

Ringer’s injection, lactated

Sodium chloride 0.4 or 0.6%

Incompatible

Dextrose 3.3% in sodium chloride 0.3%

Variable

Dextrose 5% in water

Sodium chloride 0.9%

Sodium lactate (1/6) M

Drug Compatibility

The combination of mitomycin 5–15 mg and heparin sodium 1000–10,000 units in 30 mL of 0.9% sodium chloride injection is stable for 48 hours at room temperature.100 d

Admixture CompatibilityHID

Compatible

Dexamethasone sodium phosphate

Hydrocortisone sodium succinate

Incompatible

Bleomycin sulfate

Variable

Heparin sodium

Y-Site CompatibilityHID

Compatible

Amifostine

Bleomycin sulfate

Caspofungin acetate

Cisplatin

Cyclophosphamide

Doxorubicin HCl

Droperidol

Fluorouracil

Furosemide

Granisetron HCl

Heparin sodium

Leucovorin calcium

Melphalan HCl

Methotrexate sodium

Metoclopramide HCl

Ondansetron HCl

Teniposide

Thiotepa

Vinblastine sulfate

Vincristine sulfate

Incompatible

Aztreonam

Etoposide phosphate

Filgrastim

Gemcitabine HCl

Piperacillin sodium–tazobactam sodium

Sargramostim

Topotecan HCl

Vinorelbine tartrate

Actions and Spectrum

  • Mechanism of antineoplastic activity similar to that of other alkylating agents.c

  • Enzymatic reduction of mitomycin within susceptible cells may be necessary for antineoplastic activity.c

  • Activated mitomycin appears to selectively inhibit the synthesis of deoxyribonucleic acid (DNA) by causing cross-linking of DNA.100 c d In high concentrations, may also inhibit RNA and protein synthesis.100 d

  • Active against gram-positive bacteria and some viruses; however cytotoxicity precludes use as an anti-infective agent.c

Advice to Patients

  • Importance of advising patients of potentially life-threatening hematologic (e.g., myelosuppression), respiratory, and renal toxicities associated with mitomycin therapy.100 c d

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.100 d

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., bleeding disorders).100 d

  • Importance of informing patients of other important precautionary information.100 d (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Mitomycin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection

5 mg*

Mitomycin for Injection

Mutamycin

Bristol-Myers Squibb

20 mg*

Mitomycin for Injection

Mutamycin

Bristol-Myers Squibb

40 mg

Mitomycin for Injection

Mutamycin

Bristol-Myers Squibb

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 10, 2013. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

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