Medically reviewed by Drugs.com. Last updated on Jul 6, 2019.
(al TRET a meen)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Hexalen: 50 mg [DSC]
Brand Names: U.S.
- Hexalen [DSC]
- Antineoplastic Agent, Alkylating Agent
Altretamine structurally resembles alkylating agents, although has demonstrated activity in tumors resistant to classic alkylating agents. Cytotoxic effect not fully characterized, however it is likely that after activation, metabolites form crosslinks with DNA and RNA and inhibit DNA and RNA synthesis (Perry 2012). Altretamine has demonstrated more activity in platinum-sensitive ovarian cancers than platinum-resistant disease (Alberts 2004).
Distributed into tissues high in lipid content and into tumor tissue (Damia 1995)
Hepatic; rapid and extensive demethylation to active metabolites (pentamethylmelamine and tetramethylmelamine)
Urine (90% [at 72 hours], <1% as unchanged drug)
Time to Peak
Plasma: 0.5 to 3 hours
4.7 to 10.2 hours
Use: Labeled Indications
Ovarian cancer (persistent or recurrent): Palliative treatment (single agent) of persistent or recurrent ovarian cancer after first-line treatment with a cisplatin and/or alkylating agent-based combination.
Hypersensitivity to altretamine or any component of the formulation; preexisting severe bone marrow suppression or severe neurologic toxicity
Note: Altretamine is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Hesketh 2017; Roila 2016)
Ovarian cancer (persistent or recurrent): Oral: 260 mg/m2/day in 4 divided doses for 14 or 21 days of a 28-day cycle
Refer to adult dosing.
Dosing: Adjustment for Toxicity
Temporarily withhold for 14 days or longer, and resume dose at 200 mg/m2/day for any of the following:
Platelet count <75,000/mm3
White blood cell count <2000/mm3 or granulocyte count <1000/mm3
Gastrointestinal intolerance not responsive to antiemetic regimens
Discontinue if neurotoxicity does not stabilize at 200 mg/m2/day.
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).
Altretamine is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011; Hesketh 2017; Roila 2016)
Administer total daily dose orally as 4 divided doses after meals and at bedtime.
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification
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
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy
Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. 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. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification
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. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification
Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification
Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
Monoamine Oxidase Inhibitors: Altretamine may enhance the orthostatic hypotensive effect of Monoamine Oxidase Inhibitors. Exceptions: Linezolid; Tedizolid. Monitor therapy
Multivitamins/Fluoride (with ADE): May diminish the therapeutic effect of Altretamine. Specifically, vitamin B6 (pyridoxine) supplementation may diminish the response to altretamin/cisplatin treatment. Management: In spite of its beneficial effects on altretamine-associated neurotoxicity, the potential reduction in response duration may warrant consideration of not using multivitamins containing pyridoxine (vitamin B6) with an altretamine/cisplatin regimen. Consider therapy modification
Multivitamins/Minerals (with ADEK, Folate, Iron): May diminish the therapeutic effect of Altretamine. Management: Consider avoiding use of multivitamins that contain vitamin B6 in combination with altretamine. Consider therapy modification
Multivitamins/Minerals (with AE, No Iron): May diminish the therapeutic effect of Altretamine. Management: Consider avoiding use of multivitamins that contain vitamin B6 in combination with altretamine. Consider therapy modification
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
Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy
Pyridoxine: May diminish the therapeutic effect of Altretamine. Specifically when altretamine is used in combination with Cisplatin the response duration may be diminished. Consider therapy modification
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification
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
Tricyclic Antidepressants: Altretamine may enhance the orthostatic hypotensive effect of Tricyclic Antidepressants. 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
Central nervous system: Peripheral sensory neuropathy (31%; mild: 9%; moderate-to-severe: 9%)
Gastrointestinal: Nausea and vomiting (33%; severe 1%)
Hematologic & oncologic: Anemia (33%), leukopenia (5% to 15%, grade 4: <1%)
1% to 10%:
Central nervous system: Fatigue, seizure
Hematologic & oncologic: Thrombocytopenia
Hepatic: Increased serum alkaline phosphatase
Renal: Increased blood urea nitrogen, increased serum creatinine
<1%, postmarketing, and/or case reports: Alopecia, ataxia, depression, dizziness, hepatotoxicity, mood disorder, neurotoxicity, pruritus, skin rash, vertigo
ALERT: U.S. Boxed WarningExperienced physician:
Administer only under the supervision of a physician experienced in the use of antineoplastic agents.Bone marrow suppression:
Monitor peripheral blood counts at least monthly, prior to the initiation of each course of altretamine and as clinically indicated.Neurotoxicity:
Because of the possibility of altretamine-related neurotoxicity, neurologic examination should be performed regularly during altretamine administration.
Concerns related to adverse effects:
• Bone marrow suppression: [US Boxed Warning]: Peripheral blood counts should be monitored at least monthly, prior to each cycle, and as clinically indicated. Mild to moderate dose-related hematological toxicity has been reported; may require dosage modification. With an intermittent dosing schedule, WBC and platelet nadirs occur at 3 to 4 weeks, with recovery by 6 weeks.
• Gastrointestinal toxicity: Altretamine is associated with a high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Dupuis 2011; Hesketh 2017; Roila 2016).
• Neurotoxicity: [US Boxed Warning]: Due to the potential for altretamine-associated neurologic toxicity, neurologic examinations should be done regularly during altretamine treatment. Mild to moderate neurotoxicity, including peripheral neuropathy and CNS symptoms (ataxia, dizziness, vertigo, mood disorders, and disorders of consciousness) have been reported; may require dosage modification. Neurotoxicity is generally reversible upon discontinuation. Peripheral neuropathy and CNS symptoms are more common in patients receiving a continuous high-dose daily schedule (compared to an intermittent schedule). Altretamine has been administered safely in patients with preexisting cisplatin-associated neuropathy; close monitoring is required.
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.
• MAO inhibitors: Concurrent use of altretamine and MAO inhibitors may cause severe orthostatic hypotension. Symptomatic orthostatic hypotension has been reported 4 to 7 days after concurrent administration.
• Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
CBC with differential (prior to treatment initiation, before each cycle, and regularly during treatment), neurologic examination (before each cycle and regularly during treatment). Monitor adherence.
Altretamine may cause fetal harm if administered during pregnancy. Women of childbearing potential should avoid becoming pregnant while on therapy.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Have patient report immediately to prescriber signs of infection, signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; hematuria; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), pharyngitis, shortness of breath, severe nausea, vomiting, severe loss of strength and energy, burning or numbness feeling, change in balance, mood changes, dizziness, or abnormal gait (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
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- Drug class: miscellaneous antineoplastics
Other brands: Hexalen