Version May 2024
Administer only under the supervision of a physician experienced in the use of antineoplastic agents.
Monitor peripheral blood counts at least monthly, prior to the initiation of each course of altretamine and as clinically indicated.
Because of the possibility of altretamine-related neurotoxicity, neurologic examination should be performed regularly during altretamine administration.
Note: Hexalen has been discontinued in the United States for more than 1 year.
Note: Altretamine is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Ovarian cancer (persistent or recurrent): Oral: 260 mg/m2/day in 4 divided doses for 14 or 21 days of a 28-day cycle.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2 : Utilize patient's actual body weight (full weight) for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (Ref).
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
Progressive neurotoxicity
Gastrointestinal intolerance not responsive to antiemetic regimens
Discontinue if neurotoxicity does not stabilize at 200 mg/m2/day.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
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
Gastrointestinal: Anorexia
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
Hypersensitivity to altretamine or any component of the formulation; preexisting severe bone marrow suppression or severe neurologic toxicity
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 moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (ASCO [Hesketh 2020]; MASCC/ESMO [Roila 2016]; POGO [Dupuis 2011]).
• Hepatitis B virus screening: The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
• 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:
• 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.
Other warnings/precautions:
• Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
Hexalen has been discontinued in the United States for more than 1 year.
Yes
Capsules (Hexalen Oral)
50 mg (per each): $19.08
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Altretamine is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).
Administer total daily dose orally as 4 divided doses after meals and at bedtime.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
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.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Hexalen: Brand name altretamine [U.S., Canada, and Thailand], but also brand name for hexetidine [Greece]
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: 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. Risk D: Consider therapy modification
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
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. Risk D: 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. Risk D: Consider therapy modification
Monoamine Oxidase Inhibitors (Antidepressant): Altretamine may enhance the orthostatic hypotensive effect of Monoamine Oxidase Inhibitors (Antidepressant). Risk C: 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. Risk D: Consider therapy modification
Multivitamins/Minerals (with ADEK, Folate, Iron): May diminish the therapeutic effect of Altretamine. 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. Risk D: Consider therapy modification
Multivitamins/Minerals (with AE, No Iron): May diminish the therapeutic effect of Altretamine. 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. Risk D: Consider therapy modification
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: 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. Risk D: Consider therapy modification
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: 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. Management: Consider avoiding concomitant use of pyridoxine in a altretamine/cisplatin regimen. Although pyridoxine may have beneficial effects on altretamine-associated neurotoxicity, it may reduce the duration of response to altretamine. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification
Tricyclic Antidepressants: Altretamine may enhance the orthostatic hypotensive effect of Tricyclic Antidepressants. Risk C: Monitor therapy
Women of childbearing potential should avoid becoming pregnant while on therapy.
Altretamine may cause fetal harm if administered during pregnancy.
It is not known if altretamine is present in breast milk.
Due to the potential for toxicity in the breastfed infant, breastfeeding should be discontinued during altretamine treatment.
CBC with differential (prior to treatment initiation, before each cycle, and regularly during treatment), neurologic examination (before each cycle and regularly during treatment). Hepatitis B virus screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning systemic anticancer therapy (ASCO [Hwang 2020]). Monitor adherence.
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).
Absorption: Well absorbed
Distribution: Distributed into tissues high in lipid content and into tumor tissue (Damia 1995)
Metabolism: Hepatic; rapid and extensive demethylation to active metabolites (pentamethylmelamine and tetramethylmelamine)
Half-life elimination: 4.7 to 10.2 hours
Time to peak, plasma: 0.5 to 3 hours
Excretion: Urine (90% [at 72 hours], <1% as unchanged drug)
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