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Altretamine

Medically reviewed by Drugs.com. Last updated on Apr 8, 2020.

Pronunciation

(al TRET a meen)

Index Terms

  • Hexamethylmelamine
  • HMM
  • HXM

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Hexalen: 50 mg [DSC]

Brand Names: U.S.

  • Hexalen [DSC]

Pharmacologic Category

  • Antineoplastic Agent, Alkylating Agent

Pharmacology

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)

Excretion

Urine (90% [at 72 hours], <1% as unchanged drug)

Time to Peak

Plasma: 0.5 to 3 hours

Half-Life Elimination

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.

Contraindications

Hypersensitivity to altretamine or any component of the formulation; preexisting severe bone marrow suppression or severe neurologic toxicity

Dosing: Adult

Note: Hexalen has been discontinued in the United States for more than 1 year.

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

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

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

Progressive neurotoxicity

Gastrointestinal intolerance not responsive to antiemetic regimens

Discontinue if neurotoxicity does not stabilize at 200 mg/m2/day.

Dosing: Obesity

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).

Administration

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.

Storage

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

Drug Interactions

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 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

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

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased 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. 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 (Antidepressant): Altretamine may enhance the orthostatic hypotensive effect of Monoamine Oxidase Inhibitors (Antidepressant). 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: 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 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. Consider therapy modification

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

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. 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. Consider therapy modification

Tricyclic Antidepressants: Altretamine may enhance the orthostatic hypotensive effect of Tricyclic Antidepressants. Monitor therapy

Adverse Reactions

>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

ALERT: U.S. Boxed Warning

Experienced 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.

Warnings/Precautions

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:

• 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.

Monitoring Parameters

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.

Reproductive Considerations

Women of childbearing potential should avoid becoming pregnant while on therapy.

Pregnancy Considerations

Altretamine may cause fetal harm if administered during pregnancy.

Patient Education

What is this drug used for?

• It is used to treat ovarian cancer.

• It may be given to you for other reasons. Talk with the doctor.

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; 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

• Sore throat

• Shortness of breath

• Severe loss of strength and energy

• Burning or numbness feeling

• Change in balance

• Mood changes

• Dizziness

• Abnormal gait

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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