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DRUGS & SUPPLEMENTS
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Hexinawas
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Hexinawas uses
- Indications and usage
- Contraindications
- Warnings
- Precautions
- Adverse reactions
- Overdosage
- Dosage and administration
- How supplied
- References
INDICATIONS and USAGE
Hexinawas® (altretamine) capsules is indicated for use as a single agent in the palliative treatment of patients with persistent or recurrent ovarian cancer following first-line therapy with a cisplatin and/or alkylating agent-based combination.
CONTRAINDICATIONS
Hexinawas® capsules is contraindicated in patients who have shown hypersensitivity to it. Hexinawas® capsules should not be employed in patients with preexisting severe bone marrow depression or severe neurologic toxicity. Hexinawas® capsules has been administered safely, however, to patients heavily pretreated with cisplatin and/or alkylating agents, including patients with preexisting cisplatin neuropathies. Careful monitoring of neurologic function in these patients is essential.
WARNINGS
Concurrent administration of Hexinawas® capsules and antidepressants of the monoamine oxidase 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 Hexinawas® capsules and MAO inhibitors.
Hexinawas® capsules causes mild to moderate myelosuppression and neurotoxicity. Blood counts and a neurologic examination should be performed prior to the initiation of each course of therapy and the dose of Hexinawas® capsules adjusted as clinically indicated.
Pregnancy: Category D
Hexinawas® capsules has been shown to be embryotoxic and teratogenic in rats and rabbits when given at doses 2 and 10 times the human dose. Hexinawas® capsules may cause fetal damage when administered to a pregnant woman. If Hexinawas® capsules 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. Women of childbearing potential should be advised to avoid becoming pregnant.
PRECAUTIONS
GeneralNeurologic examination should be performed regularly.
Laboratory Tests
Peripheral blood counts should be monitored at least monthly, prior to the initiation of each course of Hexinawas® capsules, and as clinically indicated.
Drug Interactions
Concurrent administration of Hexinawas® capsules and antidepressants of the MAO inhibitor class may cause severe orthostatic 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 Hexinawas® 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 Hexinawas® capsules and/or cisplatin (1).
Carcinogenesis, Mutagenesis and Impairment of Fertility
The carcinogenic potential of Hexinawas® capsules has not been studied in animals, but drugs with similar mechanisms of action have been shown to be carcinogenic. Hexinawas® capsules was weakly mutagenic when tested in strain TA100 of Salmonella typhimurium. Hexinawas® capsules administered to female rats 14 days prior to breeding through the gestation period had no adverse effect on fertility, but decreased post-natal survival at 120 mg/m2/day and was embryocidal at 240 mg/m2/day. Administration of 120 mg/m2/day Hexinawas® capsules to male rats for 60 days prior to mating resulted in testicular atrophy, reduced fertility and a possible dominant lethal mutagenic effect. Male rats treated with Hexinawas® capsules at 450 mg/m2/day for 10 days had decreased spermatogenesis, atrophy of testes, seminal vesicles and ventral prostate.
Pregnancy
Pregnancy Category D: see Warnings section.
Nursing Mothers
It is not known whether Hexinawas is excreted in human milk. Because there is a possibility of toxicity in nursing infants secondary to Hexinawas® capsules treatment of the mother, it is recommended that breast feeding be discontinued if the mother is treated with Hexinawas® capsules.
Pediatric Use
The safety and effectiveness of Hexinawas® capsules in children have not been established.
ADVERSE REACTIONS
GastrointestinalWith continuous high-dose daily Hexinawas® 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 Hexinawas® capsules dose reduction or, rarely, discontinuation of Hexinawas® 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 Hexinawas® capsules. In 2 clinical studies of single-agent Hexinawas® capsules utilizing a moderate, intermittent dose and schedule, only 1 patient discontinued Hexinawas® 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 Hexinawas® (altretamine) capsules than moderate-dose Hexinawas® capsules administered on an intermittent schedule. Neurologic toxicity has been reported to be reversible when therapy is discontinued. Data from a randomized trial of Hexinawas® 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 Hexinawas® capsules and/or cisplatin (1).
Hematologic
Hexinawas® capsules causes mild to moderate dose-related myelosuppression. Leukopenia below 3000 WBC/mm3 occurred in <15% of patients on a variety of intermittent or continuous dose regimens. Less than 1% had leukopenia below 1000 WBC/mm3. Thrombocytopenia below 50,000 platelets/mm3 was 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 with ovarian cancer previously treated with a cisplatin-based combination regimen who received single-agent Hexinawas® capsules. In one study, Hexinawas® capsules, 260 mg/m2/day, was administered for 14 days of a 28 day cycle. In another study, Hexinawas® capsules, 6-8 mg/kg/day, was administered for 21 days of a 28 day cycle.
| Adverse Experiences | % Patients |
|---|---|
| Gastrointestinal Nausea and Vomiting Mild to Moderate Severe Increased Alkaline Phosphatase | 33 32 1 9 |
| Neurologic Peripheral Sensory Neuropathy Mild Moderate to Severe Anorexia and Fatigue Seizures | 31 22 9 1 1 |
| Hematologic Leukopenia WBC 2000-2999/mm3 WBC <2000/mm3 Thrombocytopenia Platelets 75,000-99,000/mm3 Platelets <75,000/mm3 Anemia Mild Moderate to Severe | 5 4 1 9 6 3 33 20 13 |
| Renal Serum Creatinine 1.6-3.75 mg/dl BUN 25-40 mg% 41-60 mg% >60 mg% | 7 9 5 3 1 |
Additional adverse reaction information is available from 13 single-agent Hexinawas 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 Hexinawas (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, skin rash, pruritus and alopecia, each occurring in <1% of patients.
OVERDOSAGE
No case of acute overdosage in humans has been described. The oral LD50 dose in rats was 1050 mg/kg and 437 mg/kg in mice.
DOSAGE AND ADMINISTRATION
Hexinawas® capsules is administered orally. Doses are calculated on the basis of body surface area.
Hexinawas® capsules may be administered either for 14 or 21 consecutive days in a 28 day cycle at a dose of 260 mg/m2/day. The total daily dose should be given as 4 divided oral doses after meals and at bedtime. There is no pharmacokinetic information supporting this dosing regimen and the effect of food on Hexinawas® capsules bioavailability or pharmacokinetics has not been evaluated.
Hexinawas® capsules should be temporarily discontinued (for 14 days or longer) and subsequently restarted at 200 mg/m2/day for any of the following situations:
1) Gastrointestinal intolerance unresponsive to symptomatic measures;
2) White blood count <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 schedule, Hexinawas® capsules should be discontinued indefinitely.
Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published (2-9). There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.
HOW SUPPLIED
Hexinawas® (altretamine) capsules is available in 50 mg clear, hard gelatin capsules imprinted with the following inscription:
USB 001.
Bottles of 100 capsules
(NDC 62856-001-10)
Store up to 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F).
REFERENCES
- Wiernik PH, et al. Hexamethylmelamine and Low or Moderate Dose Cisplatin With or Without Pyridoxine for Treatment of Advanced Ovarian Carcinoma: A Study of the Eastern Cooperative Oncology Group. Cancer Invest. 1992; 10(1): 1-9.
- ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice. Pittsburgh, Pa: Oncology Nursing Society; 1999:32-41.
- U.S. Department of Health and Human Services. Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs. Washington DC: Division of Safety, National Institutes of Health; 1983 Public Health Service publication NIH 83-2621.
- AMA Council on Scientific Affairs. Guidelines for Handling Parenteral Antineoplastics. JAMA. 1985; 253:1590-1591.
- National Study Commission on Cytotoxic Exposure. Recommendations for Handling Cytotoxic Agents. Boston, MA: Available from Louis P. Jeffrey, Chairman, National Study Commission on Cytotoxic Exposure, Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, MA 02115; 1987.
- Clinical Oncological Society of Australia: Guidelines and Recommendations for Safe Handling of Antineoplastic Agents. Med J Australia. 1983;1:426-428.
- Jones RB, Frank R, Mass T. Safe Handling of Chemotherapeutic Agents: A Report from the Mount Sinai Medical Center. CA Cancer J Clin. 1983;33:258-263.
- American Society of Hospital Pharmacists. ASHP Technical Assistance Bulletin on Handling Cytotoxic and Hazardous Drugs. Am J Hosp Pharm. 1990; 47:1033-1049.
- OSHA Work Practice Guidelines. Controlling Occupational Exposure to Hazardous Drugs. Am J Health Syst Pharm. 1996;53:1669-1685.
Hexinawas® (altretamine) capsules is a registered trademark of Eisai Inc.
Manufactured by:
AAIPharma Inc.
Wilmington, NC 28405
Manufactured for:
Eisai Inc.
Woodcliff Lake, NJ 07677
For Medical Inquiries call: 1-877-873-4724
Revision Date May 2009
Hexinawas pharmaceutical active ingredients containing related brand and generic drugs:
Hexinawas available forms, composition, doses:
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.