Side Effects of Hexalen (altretamine)

Hexalen(altretamine) is an anti-cancer(antineoplastic) drug used to treatovarian cancer. The precise mechanism by which Hexalen exerts its anti-cancereffect is unknown.

Common side effects of Hexalen include:

• nausea,
• vomiting,
• 四肢麻木和刺痛,
• central nervous system symptoms (mood disorders, disorders of consciousness, loss of coordination),
• dizziness, and
• spinning sensation (vertigo).

Serious side effects of Hexalen include:

• severe numbness, tingling, orcoldfeeling in your hands orfeet;
• severe or continuousvomiting;
• fever,chills,flu symptoms,
• mouth sores,
• pale skin,
• easy bruisingor bleeding,
• unusual弱点;
• lightheadedness;
• severedizzinessor spinning sensation;
• seizures(convulsions); and
• upperstomach pain,
• dark urine,
• clay-colored stools,
• jaundice(yellowing of the skin or eyes).

Drug interactionsof Hexalen include:

• monoamine oxidase inhibitors(MAOIs),
• cimetidine,
• pyridoxine, and
• "live"vaccines.

Hexalen may harm a fetus when administered to apregnantwoman. Women of childbearing potential are advised to avoidbecoming pregnantwhile using Hexalen.

It is unknown if Hexalen is secreted inhuman milk. Since Hexalen may be toxic tonursinginfants,breastfeedingis not recommended during treatment with Hexalen.

Common side effects are:

• Nauseaand vomiting
• Peripheral neuropathy(abnormal function of the sensory nerves of the arms and legs giving rise to symptoms such as numbness, tingling, etc.) and central nervous system symptoms (mood disorders, disorders of consciousness,ataxia)
• dizziness, and
• vertigo.

Gastrointestinal

• With continuous high-dose daily Hexalen (altretamine) capsules, nausea and vomiting of gradual onset occur frequently.
• Although in most instances these symptoms are controllable with anti-emetics, at times the severity requires Hexalen (altretamine) capsules dose reduction or, rarely, discontinuation of Hexalen (altretamine) capsules therapy.
• In some instances, a tolerance of these symptoms develops after several weeks of therapy. The incidence and severity of nausea and vomiting are reduced with moderate-dose administration of Hexalen (altretamine) capsules.
• In 2 clinical studies of single-agent Hexalen (altretamine) capsules utilizing a moderate, intermittent dose and schedule, only 1 patient (1%) discontinued Hexalen (altretamine) capsules due to severe nausea and vomiting.

Neurotoxicity

• Peripheral neuropathy and central nervous system symptoms (mood disorders, disorders of consciousness,ataxia, dizziness,vertigo) have been reported.
• They are more likely to occur in patients receiving continuous high-dose daily Hexalen (altretamine) (altretamine) capsules than moderate-dose Hexalen (altretamine) capsules administered on an intermittent schedule.
• 神经毒性的报道reversible when therapy is discontinued.
• Data from a randomized trial of Hexalen (altretamine) capsules and cisplatin plus or minus pyridoxine inovarian cancerindicated that pyridoxine significantly reduced neurotoxicity; however, it adversely affected response duration suggesting that pyridoxine should not be administered with Hexalen (altretamine) capsules and/or cisplatin (1).

Hematologic

• Hexalen (altretamine) capsules causes mild to moderate dose-related myelosuppression.
• Leukopenia below 3000 WBC/mm³occurred in <15% of patients on a variety of intermittent or continuous dose regimens. Less than 1% had leukopenia below 1000 WBC/mm³.
• Thrombocytopeniabelow 50,000 platelets/mm³was seen in <10% of patients.
• When given in doses of 8-12 mg/kg/day over a 21 day course, nadirs of leukocyte and platelet counts were reached by 3-4 weeks, and normal counts were regained by 6 weeks.
• With continuous administration at doses of 6-8 mg/kg/day, nadirs are reached in 6-8 weeks (median).
• Data in the following table are based on the experience of 76 patients withovarian cancerpreviously treated with a cisplatin-based combination regimen who received single-agent Hexalen (altretamine) capsules.
• In one study, Hexalen (altretamine) capsules, 260 mg/m²/day, was administered for 14 days of a 28 day cycle. In another study, Hexalen (altretamine) capsules, 6-8 mg/kg/day, was administered for 21 days of a 28-day cycle.

ADVERSE EXPERIENCES IN 76 PREVIOUSLY TREATED OVARIANCANCERPATIENTS RECEIVING SINGLE-AGENT Hexalen (altretamine) CAPSULES

• Additional adverse reaction information is available from 13 single-agent altretamine studies (total of 1014 patients) conducted under the auspices of the National Cancer Institute.
• The treated patients had a variety of tumors and many were heavily pretreated with other chemotherapies; most of these trials utilized high, continuous daily doses of altretamine (612 mg/kg/day).
• In general, adverse reaction experiences were similar in the two trials described above. Additional toxicities, not reported in the above table, included hepatic toxicity, skinrash, pruritus andalopecia,每一个发生in <1% of patients.

• Concurrent administration of Hexalen (altretamine) capsules and抗抑郁药of the MAO inhibitor class may cause severeorthostatic hypotension.
• Cimetidine, an inhibitor of microsomal drug metabolism, increased altretamine's half-life and toxicity in a rat model.
• Data from a randomized trial of Hexalen (altretamine) capsules and cisplatin plus or minus pyridoxine in ovarian cancer indicated that pyridoxine significantly reduced neurotoxicity; however, it adversely affected response duration suggesting that pyridoxine should not be administered with Hexalen (altretamine) capsules and/or cisplatin (1).