MitoMYcin (Systemic)

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as a shot into a vein.
• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

Anal cancer

Data from a multicenter, phase III, randomized, controlled study supports the use of mitomycin (in combination with fluorouracil and radiation therapy) in the treatment of anal cancer [Ajani 2008]. Data from another randomized, phase III study also support the use of mitomycin (in combination with fluorouracil and radiation therapy) in the treatment of anal cancer [Flam 1996]. Additional data support the use of mitomycin in combination with capecitabine and radiation therapy [Meulendijks 2014], [Thind 2014].

Bladder cancer

Data from a multicenter phase III trial in muscle invasive bladder cancer supports the use of systemic mitomycin (in combination with concurrent radiation and fluorouracil) for the treatment of this condition[James 2012]. Additionally, data from phase III and IV trials support the use of intravesicular mitomycin in the management of nonmuscle invasive bladder cancer [Au 2001], [Friedrich 2007], [O’Brien 2013].

Based on the American Urological Association (AUA)/Society of Urologic Oncology (SUO) Guideline for the Diagnosis and Treatment of Nonmuscle Invasive Bladder Cancer: (Stages Ta, T1 and Tis): 2016, mitomycin administered intravesicularly for the treatment of low or intermediate risk nonmuscle invasive bladder cancer is effective and recommended in the management of this condition [Chang 2016]

Cervical cancer, recurrent or metastatic

Data from a small phase II trial suggests that mitomycin (in combination with cisplatin) may be an option for management of recurrent or metastatic cervical cancer [Wagenaar 2001]. Additional data may be necessary to further define the role of mitomycin in the management of this condition.

Esophageal cancer, advanced

Data from a randomized phase III trial suggests that mitomycin (in combination with cisplatin and fluorouracil; MCF regimen) may be an effective regimen in the treatment of advanced esophageal cancer [Ross 2002]. Additional data may be necessary to further define the role of mitomycin in the management of this condition.

Vulvar cancer, advanced

Data from a small prospective phase II trial supports the use of mitomycin (in combination with fluorouracil and radiation) for the treatment of locally advanced or recurrent vulvar carcinoma [Landoni 1996]. Additional data may be necessary to further define the role of mitomycin in the management of this condition.

Hypersensitivity to mitomycin or any component of the formulation; thrombocytopenia; coagulation disorders, or other increased bleeding tendency

Refer to adult dosing.

ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs, 2012).

Antineoplastic Agents (Vinca Alkaloids): May enhance the adverse/toxic effect of MitoMYcin (Systemic). Specifically, the risk of pulmonary toxicity may be increased. Monitor therapy

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Avoid combination

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Consider therapy modification

Lumacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Consider therapy modification

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination

Concerns related to adverse effects:

• Bladder fibrosis/contraction: Bladder fibrosis/contraction has been reported with intravesical administration (unlabeled administration route).

• Bone marrow suppression: [US Boxed Warning]: Bone marrow suppression (thrombocytopenia and leukopenia) is common and may be severe and/or contribute to infections. WBC and platelet nadir usually occurs at 4 weeks, although may occur at up to 8 weeks; recovery occurs within 10 weeks. Fatalities due to sepsis have been reported; monitor for infections. Myelosuppression is dose-limiting, delayed in onset, and cumulative; therefore, monitor blood counts closely during and for at least 8 weeks following treatment; treatment delay or dosage adjustment may be required for significant thrombocytopenia (platelets <100,000/mm3) or leukopenia (WBC<4,000/mm3) or a progressive decline in either value.

• Extravasation: Mitomycin is a potent vesicant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation. May cause necrosis and tissue sloughing; delayed erythema and/or ulceration have been reported.

• Heart failure: In a scientific statement from the American Heart Association, mitomycin has been determined to be an agent that may either cause reversible direct myocardial toxicity or exacerbate underlying myocardial dysfunction (magnitude: moderate) (AHA [Page 2016]).

• Hemolytic-uremic syndrome: [US Boxed Warning]: Hemolytic-uremic syndrome (HUS) has been reported (incidence not defined); condition usually involves microangiopathic hemolytic anemia (hematocrit ≤25%), thrombocytopenia (≤100,000/mm3), and irreversible renal failure (serum creatinine ≥1.6 mg/dL). HUS may occur at any time (either with single agent or combination therapy), is generally associated with single doses ≥60 mg, and HUS symptoms may be exacerbated by blood transfusion. Other less common effects may include pulmonary edema, neurologic abnormalities, and hypertension. A high mortality from HUS has been reported.

• Pulmonary toxicity: Cases of acute respiratory distress syndrome (ARDS) have been reported in patients receiving mitomycin in combination with other chemotherapy who were maintained at FIO2 concentrations >50% perioperatively; use caution to provide only enough oxygen to maintain adequate arterial saturation and avoid overhydration. Pulmonary toxicity has also been reported as dyspnea with nonproductive cough and appearance of pulmonary infiltrates on radiograph; discontinue therapy if pulmonary toxicity occurs and other potential etiologies have been ruled out.

Disease-related concerns:

• Renal impairment: Do not administer if serum creatinine is >1.7 mg/dL; monitor for renal toxicity.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

• Vinca alkaloids: Shortness of breath and bronchospasm have been reported in patients receiving vinca alkaloids in combination with mitomycin or who received mitomycin previously; this acute respiratory distress has occurred within minutes to hours following the vinca alkaloid; may be managed with bronchodilators, steroids and/or oxygen.

Other warnings/precautions:

• Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.

Adverse events have been observed in animal reproduction studies.