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DRUGS & SUPPLEMENTS
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Hexastat® (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.
Hexastat® capsules is contraindicated in patients who have shown hypersensitivity to it. Hexastat® capsules should not be employed in patients with preexisting severe bone marrow depression or severe neurologic toxicity. Hexastat® 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.
Concurrent administration of Hexastat® 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 Hexastat® capsules and MAO inhibitors.
Hexastat® 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 Hexastat® capsules adjusted as clinically indicated.
Pregnancy: Category D
Hexastat® capsules has been shown to be embryotoxic and teratogenic in rats and rabbits when given at doses 2 and 10 times the human dose. Hexastat® capsules may cause fetal damage when administered to a pregnant woman. If Hexastat® 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.
Neurologic examination should be performed regularly.
Laboratory Tests
Peripheral blood counts should be monitored at least monthly, prior to the initiation of each course of Hexastat® capsules, and as clinically indicated.
Drug Interactions
Concurrent administration of Hexastat® 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 Hexastat® 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 Hexastat® capsules and/or cisplatin (1).
Carcinogenesis, Mutagenesis and Impairment of Fertility
The carcinogenic potential of Hexastat® capsules has not been studied in animals, but drugs with similar mechanisms of action have been shown to be carcinogenic. Hexastat® capsules was weakly mutagenic when tested in strain TA100 of Salmonella typhimurium. Hexastat® 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 Hexastat® 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 Hexastat® 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 Hexastat is excreted in human milk. Because there is a possibility of toxicity in nursing infants secondary to Hexastat® capsules treatment of the mother, it is recommended that breast feeding be discontinued if the mother is treated with Hexastat® capsules.
Pediatric Use
The safety and effectiveness of Hexastat® capsules in children have not been established.
With continuous high-dose daily Hexastat® 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 Hexastat® capsules dose reduction or, rarely, discontinuation of Hexastat® 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 Hexastat® capsules. In 2 clinical studies of single-agent Hexastat® capsules utilizing a moderate, intermittent dose and schedule, only 1 patient discontinued Hexastat® 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 Hexastat® (altretamine) capsules than moderate-dose Hexastat® capsules administered on an intermittent schedule. Neurologic toxicity has been reported to be reversible when therapy is discontinued. Data from a randomized trial of Hexastat® 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 Hexastat® capsules and/or cisplatin (1).
Hematologic
Hexastat® 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 Hexastat® capsules. In one study, Hexastat® capsules, 260 mg/m2/day, was administered for 14 days of a 28 day cycle. In another study, Hexastat® 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 Hexastat 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 Hexastat (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.
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.
Hexastat® capsules is administered orally. Doses are calculated on the basis of body surface area.
Hexastat® 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 Hexastat® capsules bioavailability or pharmacokinetics has not been evaluated.
Hexastat® 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, Hexastat® 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.
Hexastat® (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).
Hexastat® (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
Depending on the reaction of the Hexastat after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Hexastat not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.
Is Hexastat addictive or habit forming?Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
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The information was verified by Dr. Rachana Salvi, MD Pharmacology