Hexalen

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Hexalen

Classes

Other Alkylating Agents

Administration

 
CAUTION: Observe and exercise appropriate precautions for handling, preparing, and administering cytotoxic drugs.

Oral Administration

Administer orally after meals and at bedtime.

Adverse Reactions
Severe

azotemia / Delayed / 9.0-9.0
vomiting / Early / 1.0-1.0
nausea / Early / 1.0-1.0
seizures / Delayed / 1.0-1.0

Moderate

anemia / Delayed / 33.0-33.0
peripheral neuropathy / Delayed / 31.0-31.0
thrombocytopenia / Delayed / 9.0-9.0
elevated hepatic enzymes / Delayed / 9.0-9.0
leukopenia / Delayed / 5.0-5.0
bone marrow suppression / Delayed / Incidence not known
depression / Delayed / Incidence not known
neurotoxicity / Early / Incidence not known
confusion / Early / Incidence not known
ataxia / Delayed / Incidence not known

Mild

anorexia / Delayed / 1.0-1.0
fatigue / Early / 1.0-1.0
pruritus / Rapid / 0-1.0
alopecia / Delayed / 0-1.0
rash / Early / 0-1.0
dizziness / Early / Incidence not known
vertigo / Early / Incidence not known

Boxed Warning
Bone marrow suppression, herpes infection, infection, neutropenia, radiation therapy, requires an experienced clinician, thrombocytopenia, varicella, viral infection

Altretamine is contraindicated in patients with pre-existing severe bone marrow suppression. Patients with preexisting bone marrow suppression, including neutropenia or thrombocytopenia, should not receive altretamine until their counts recover or, if therapy is necessary, receive a lower dose. Altretamine therapy requires an experienced clinician and should only be administered by clinicians  experienced with the use of antineoplastic agents. Altretamine should be temporarily discontinued for 14 days or longer and subsequently restarted at a reduced dose (see Dosage) for leukopenia (WBC < 2000/mm3), neutropenia (granulocyte count < 1000/mm3) or thrombocytopenia (platelet count < 75,000/mm3). Peripheral blood counts should be monitored at least monthly, prior to the initiation of each course of altretamine, and as clinically indicated. Caution should be used in patients who have had previous cytotoxic agents or radiation therapy. In addition, patients with an active infection should be treated prior to receiving altretamine. Patients with a history of varicella zoster, other herpes infection (e.g., herpes simplex), or other viral infection are at risk for reactivation of the infection when treated with chemotherapy.

Common Brand Names

Hexalen

Dea Class

Rx

Description

Synthetic antineoplastic agent used for ovarian tumors resistant to alkylating agents; has a unique MOA; also known as hexamethylmelamine, often abbreviated HMM.

Dosage And Indications
For the palliative treatment of recurrent or persistent ovarian cancer as a single agent following first-line combination chemotherapy.
NOTE: Altretamine has been designated an orphan drug by the FDA for this indication.
Oral dosage Adults

260 mg/m2/day PO, given as 4 divided doses after meals and at bedtime, for 14 or 21 days in a 28 day cycle. Temporarily discontinue the drug (for 14 days or longer) and then restart at 200 mg/m2/day PO for any of the following: 1) GI intolerance unresponsive to symptomatic measures; 2) WBC < 2000/mm3 or granulocyte count < 1000/mm3; 3) Platelet count < 75,000/mm3; 4) Progressive neurotoxicity. If neurologic symptoms fail to stabilize on the reduced dose, discontinue the drug indefinitely.

Dosing Considerations
Hepatic Impairment

No formal pharmacokinetic studies or recommendations in these patients are available.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Drug Interactions

Acetaminophen; Butalbital: (Minor) Because altretamine undergoes significant metabolism by the cytochrome P450 system, agents that stimulate CYP450 enzymes, such as barbiturates, increase the metabolism of altretamine and may result in decreased therapeutic effects.
Acetaminophen; Butalbital; Caffeine: (Minor) Because altretamine undergoes significant metabolism by the cytochrome P450 system, agents that stimulate CYP450 enzymes, such as barbiturates, increase the metabolism of altretamine and may result in decreased therapeutic effects.
Acetaminophen; Butalbital; Caffeine; Codeine: (Minor) Because altretamine undergoes significant metabolism by the cytochrome P450 system, agents that stimulate CYP450 enzymes, such as barbiturates, increase the metabolism of altretamine and may result in decreased therapeutic effects.
Aldesleukin, IL-2: (Moderate) The safety and efficacy of aldesleukin, IL 2 in combination with any antineoplastic agents have not been established; however, concurrent or sequential use of these agents is common but results in various pharmacodynamic drug interaction risks.
Alpha interferons: (Moderate) Additive myelosuppressive effects may be seen when alpha interferons are given concurrently with other myelosuppressive agents, such as antineoplastic agents or immunosuppressives.
Alteplase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Amlodipine; Celecoxib: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Amobarbital: (Minor) Because altretamine undergoes significant metabolism by the cytochrome P450 system, agents that stimulate CYP450 enzymes, such as barbiturates, increase the metabolism of altretamine and may result in decreased therapeutic effects.
Anticoagulants: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Antithrombin III: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Antithymocyte Globulin: (Moderate) Because antithymocyte globulin is an immunosuppressant, additive affects may be seen with other immunosuppressives or antineoplastic agents. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk of infection or other side effects.
Apixaban: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Argatroban: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Because altretamine undergoes significant metabolism by the cytochrome P450 system, agents that stimulate CYP450 enzymes, such as barbiturates, increase the metabolism of altretamine and may result in decreased therapeutic effects.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Minor) Because altretamine undergoes significant metabolism by the cytochrome P450 system, agents that stimulate CYP450 enzymes, such as barbiturates, increase the metabolism of altretamine and may result in decreased therapeutic effects.
Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Minor) Because altretamine undergoes significant metabolism by the cytochrome P450 system, agents that stimulate CYP450 enzymes, such as barbiturates, increase the metabolism of altretamine and may result in decreased therapeutic effects.
Azelastine; Fluticasone: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Bacillus Calmette-Guerin Vaccine, BCG: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Barbiturates: (Minor) Because altretamine undergoes significant metabolism by the cytochrome P450 system, agents that stimulate CYP450 enzymes, such as barbiturates, increase the metabolism of altretamine and may result in decreased therapeutic effects.
Beclomethasone: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Belladonna Alkaloids; Ergotamine; Phenobarbital: (Minor) Because altretamine undergoes significant metabolism by the cytochrome P450 system, agents that stimulate CYP450 enzymes, such as barbiturates, increase the metabolism of altretamine and may result in decreased therapeutic effects.
Betamethasone: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Betrixaban: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Bivalirudin: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Budesonide: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Budesonide; Formoterol: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Budesonide; Glycopyrrolate; Formoterol: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Butabarbital: (Minor) Because altretamine undergoes significant metabolism by the cytochrome P450 system, agents that stimulate CYP450 enzymes, such as barbiturates, increase the metabolism of altretamine and may result in decreased therapeutic effects.
Carbamazepine: (Moderate) Myelosuppressive antineoplastic agents and radiation therapy possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution. Dosage adjustments may be necessary. Monitor patient closely.
Celecoxib: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ciclesonide: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Cimetidine: (Minor) Cimetidine, a known inhibitor of the cytochrome P-450 enzyme system, can decrease the hepatic metabolism of altretamine, which could result in delayed elimination and increased blood concentrations.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
Corticosteroids: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Cortisone: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Dabigatran: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Dalteparin: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Danaparoid: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Deflazacort: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Desirudin: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Dexamethasone: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Diclofenac: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diclofenac; Misoprostol: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diflunisal: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Diphenhydramine; Ibuprofen: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Diphenhydramine; Naproxen: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Echinacea: (Major) Echinacea possesses immunostimulatory activity and may theoretically reduce the response to drugs that alter immune system activity like antineoplastic drugs. Although documentation is lacking, coadministration of echinacea with immunosuppressants is not recommended by some resources.
Edoxaban: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Enoxaparin: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Esomeprazole; Naproxen: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Etodolac: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Famotidine; Ibuprofen: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Fenoprofen: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Filgrastim, G-CSF: (Major) Because antineoplastic agents exert their toxic effects against rapidly growing cells, such as hematopoietic progenitor cells, filgrastim is contraindicated for use in patients in the period 24 hours before through 24 hours after treatment with cytotoxic chemotherapy.
Fludrocortisone: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Flunisolide: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Flurbiprofen: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Fluticasone: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Fluticasone; Salmeterol: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Fluticasone; Umeclidinium; Vilanterol: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Fluticasone; Vilanterol: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Fondaparinux: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Formoterol; Mometasone: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Fosphenytoin: (Minor) Altretamine undergoes significant metabolism by the cytochrome P450 system. Fosphenytoin is known to induce CYP450 enzymes. In theory, co-administration may increase the rate of altretamine metabolism thus decreasing altretamine effect; one study in mice has suggested that hepatic enzyme induction antagonizes antitumor activity of altretamine.
Heparin: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Hydrocodone; Ibuprofen: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Hydrocortisone: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Ibuprofen: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Oxycodone: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ibuprofen; Pseudoephedrine: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Indomethacin: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Influenza Virus Vaccine: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Intranasal Influenza Vaccine: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Isocarboxazid: (Moderate) Concurrent administration of altretamine and monoamine oxidase (MAO) inhibitor antidepressants may cause severe orthostatic hypotension. Four patients, all over 60 years of age, were reported to have experienced symptomatic hypotension after 4 to 7 days of concomitant therapy with altretamine and MAOIs. The mechanism of the interaction is not clear.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Minor) Altretamine undergoes significant metabolism by the cytochrome P450 system. Rifampin is known to induce CYP450 enzymes. In theory, co-administration may increase the rate of altretamine metabolism thus decreasing altretamine effect; one study in mice has suggested that hepatic enzyme induction antagonizes antitumor activity of altretamine.
Isoniazid, INH; Rifampin: (Minor) Altretamine undergoes significant metabolism by the cytochrome P450 system. Rifampin is known to induce CYP450 enzymes. In theory, co-administration may increase the rate of altretamine metabolism thus decreasing altretamine effect; one study in mice has suggested that hepatic enzyme induction antagonizes antitumor activity of altretamine.
Ketoprofen: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Ketorolac: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Lansoprazole; Naproxen: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Lepirudin: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Live Vaccines: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Measles/Mumps/Rubella Vaccines, MMR: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Meclofenamate Sodium: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Mefenamic Acid: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Meloxicam: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Mephobarbital: (Minor) Because altretamine undergoes significant metabolism by the cytochrome P450 system, agents that stimulate CYP450 enzymes, such as barbiturates, increase the metabolism of altretamine and may result in decreased therapeutic effects.
Methohexital: (Minor) Because altretamine undergoes significant metabolism by the cytochrome P450 system, agents that stimulate CYP450 enzymes, such as barbiturates, increase the metabolism of altretamine and may result in decreased therapeutic effects.
Methylprednisolone: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Mometasone: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Monoamine oxidase inhibitors: (Moderate) Concurrent administration of altretamine and monoamine oxidase (MAO) inhibitor antidepressants may cause severe orthostatic hypotension. Four patients, all over 60 years of age, were reported to have experienced symptomatic hypotension after 4 to 7 days of concomitant therapy with altretamine and MAOIs. The mechanism of the interaction is not clear.
Nabumetone: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen; Pseudoephedrine: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Naproxen; Sumatriptan: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Nonsteroidal antiinflammatory drugs: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Oxaprozin: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Palifermin: (Moderate) Palifermin should not be administered within 24 hours before, during infusion of, or within 24 hours after administration of antineoplastic agents.
Pegfilgrastim: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Penicillamine: (Major) Do not use penicillamine with antineoplastic agents due to the increased risk of developing severe hematologic and renal toxicity.
Pentobarbital: (Minor) Because altretamine undergoes significant metabolism by the cytochrome P450 system, agents that stimulate CYP450 enzymes, such as barbiturates, increase the metabolism of altretamine and may result in decreased therapeutic effects.
Pentosan: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Phenelzine: (Moderate) Concurrent administration of altretamine and monoamine oxidase (MAO) inhibitor antidepressants may cause severe orthostatic hypotension. Four patients, all over 60 years of age, were reported to have experienced symptomatic hypotension after 4 to 7 days of concomitant therapy with altretamine and MAOIs. The mechanism of the interaction is not clear.
Phenobarbital: (Minor) Because altretamine undergoes significant metabolism by the cytochrome P450 system, agents that stimulate CYP450 enzymes, such as barbiturates, increase the metabolism of altretamine and may result in decreased therapeutic effects.
Phenytoin: (Minor) Altretamine undergoes significant metabolism by the cytochrome P450 system. Phenytoin is known to induce CYP450 enzymes. In theory, co-administration may increase the rate of altretamine metabolism thus decreasing altretamine effect; one study in mice has suggested that hepatic enzyme induction antagonizes antitumor activity of altretamine.
Piroxicam: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Platelet Inhibitors: (Moderate) An additive risk of bleeding may occur when platelet inhibitors is used with agents that cause clinically significant thrombocytopenia including antineoplastic agents, such as altretamine.
Prednisolone: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Prednisone: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Primidone: (Minor) Because altretamine undergoes significant metabolism by the cytochrome P450 system, agents that stimulate CYP450 enzymes, such as barbiturates, increase the metabolism of altretamine and may result in decreased therapeutic effects.
Pyridoxine, Vitamin B6: (Major) Data from a randomized trial of altretamine and cisplatin plus or minus pyridoxine, vitamin B6 in ovarian cancer indicated that pyridoxine significantly reduced drug-induced neurotoxicity; however, it adversely affected response duration suggesting that pyridoxine should not be administered with altretamine and/or cisplatin.
Rasagiline: (Major) Avoid concomitant use of MAOIs during altretamine therapy whenever possible. Concurrent administration of altretamine and medications in the monoamine oxidase (MAO) inhibitor class may cause severe orthostatic hypotension. Four patients, all over 60 years of age, were reported to have experienced symptomatic hypotension after 4 to 7 days of concomitant therapy with altretamine and MAO inhibitors (MAOIs). The mechanism of the interaction is not clear.
Reteplase, r-PA: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Rifampin: (Minor) Altretamine undergoes significant metabolism by the cytochrome P450 system. Rifampin is known to induce CYP450 enzymes. In theory, co-administration may increase the rate of altretamine metabolism thus decreasing altretamine effect; one study in mice has suggested that hepatic enzyme induction antagonizes antitumor activity of altretamine.
Rivaroxaban: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Rofecoxib: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Rotavirus Vaccine: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Rubella Virus Vaccine Live: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Secobarbital: (Minor) Because altretamine undergoes significant metabolism by the cytochrome P450 system, agents that stimulate CYP450 enzymes, such as barbiturates, increase the metabolism of altretamine and may result in decreased therapeutic effects.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Smallpox Vaccine, Vaccinia Vaccine: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Streptokinase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Sulindac: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Tbo-Filgrastim: (Major) Because antineoplastic agents exert their toxic effects against rapidly growing cells, such as hematopoietic progenitor cells, filgrastim is contraindicated for use in patients in the period 24 hours before through 24 hours after treatment with cytotoxic chemotherapy.
Tenecteplase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Thiopental: (Minor) Because altretamine undergoes significant metabolism by the cytochrome P450 system, agents that stimulate CYP450 enzymes, such as barbiturates, increase the metabolism of altretamine and may result in decreased therapeutic effects.
Thrombolytic Agents: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Tinzaparin: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Tolmetin: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Tranylcypromine: (Moderate) Concurrent administration of altretamine and monoamine oxidase (MAO) inhibitor antidepressants may cause severe orthostatic hypotension. Four patients, all over 60 years of age, were reported to have experienced symptomatic hypotension after 4 to 7 days of concomitant therapy with altretamine and MAOIs. The mechanism of the interaction is not clear.
Triamcinolone: (Minor) Concurrent use of altretamine with other agents which cause bone marrow or immune suppression such as corticosteroids may result in additive effects.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Typhoid Vaccine: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Urokinase: (Moderate) An increased risk of bleeding may occur when thrombolytic agents are used following agents that cause clinically significant thrombocytopenia including antineoplastic agents.
Valdecoxib: (Major) Altretamine causes mild to moderate dose-related myelosuppression. Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant NSAIDs. In addition, large doses of salicylates (>= 3-4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding.
Varicella-Zoster Virus Vaccine, Live: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.
Warfarin: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Yellow Fever Vaccine, Live: (Severe) Live virus vaccines should generally not be administered to an immunosuppressed patient. Live virus vaccines may induce the illness they are intended to prevent and are generally contraindicated for use during immunosuppressive treatment. The immune response of the immunocompromised patient to vaccines may be decreased, even despite alternate vaccination schedules or more frequent booster doses. If immunization is necessary, choose an alternative to live vaccination, or, consider a delay or change in the immunization schedule. Practitioners should refer to the most recent CDC guidelines regarding vaccination of patients who are receiving drugs that adversely affect the immune system.

How Supplied

Hexalen Oral Cap: 50mg

Maximum Dosage
Adults

260 mg/m2/day PO.

Mechanism Of Action

Altretamine must be metabolized to generate the active cytotoxic agent(s); metabolites can form covalent adducts with tissue macromolecules, including DNA, both in vitro and in vivo. It is not known whether this is relevant to the antitumor activity. One of the metabolites is further converted to formaldehyde, which may contribute to its activity. Altretamine is active in ovarian tumors resistant to alkylating agents such as cisplatin and cyclophosphamide.

Pharmacokinetics

Altretamine is administered orally. Altretamine is weakly bound to plasma proteins and distributes to pleural and ascitic fluids. The clinical consequences of drug penetration into ascites or pleural effusions have not been described. Altretamine undergoes extensive mono- and di-demethylation in the liver, resulting in variable altretamine plasma levels. The half-life in the beta-phase of elimination is 4.7—10.2 hours. Urinary excretion of a single dose is 90% after 3 days, consisting almost entirely of N-demethylated metabolites. Only 1% of a dose is eliminated as unchanged drug in the urine. Fractions of a dose can be found in expired air and feces.

Oral Route

Altretamine is rapidly absorbed from the GI tract. There is considerable interpatient variability in the amount absorbed. Absorption is not dose-dependent. Peak plasma concentrations are achieved in 0.5—3 hours.

Pregnancy And Lactation
Pregnancy

Altretamine is classified as FDA pregnancy category D and may cause teratogenic effects if administered during pregnancy. Embryotoxic and teratogenic effects have been reported in animal studies. If altretamine is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be apprised of the potential hazard to the fetus. Females of childbearing potential should be advised to avoid becoming pregnant.

It is not known whether altretamine is excreted in human milk. According to the manufacturer, it is recommended that breast-feeding be discontinued if altretamine is given to a nursing mother due to the possibility of toxicity in the infant.