A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Hexalen Side Effects, and Drug Interactions - Altretamine
Hexalen Side Effects, and Drug Interactions - Altretamine
SIDE EFFECTS
Gastrointestinal
With continuous high-dose daily HEXALEN, 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 dose
reduction or, rarely, discontinuation of HEXALEN 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. In
2 clinical studies of single-agent
HEXALEN utilizing a moderate, intermittent dose
and schedule, only 1 patient
(1%) discontinued HEXALEN 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) than moderate-dose HEXALEN administered
on an intermittent schedule.
Neurologic toxicity has been
reported to be reversible when therapy
is discontinued. Data from a randomized trial of HEXALEN 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
and/or cisplatin (1).
Hematologic
HEXALEN 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 HEXALEN.
In one study, HEXALEN, 260 mg/m2/day,
was administered for 14 days of a 28 day cycle. In
another study, HEXALEN, 6-8 mg/kg/day, was administered for 21 days of
a 28 day cycle.
ADVERSE EXPERIENCES IN 76 PREVIOUSLY TREATED OVARIAN
CANCER PATIENTS RECEIVING SINGLE-AGENT HEXALEN
| Adverse Experiences |
% Patients
|
| Gastrointestinal |
| Nausea and
Vomiting |
|
Mild to Moderate
|
|
Severe
|
|
| Increased Alkaline
Phosphatase |
|
| Neurologic
|
| Peripheral
Sensory Neuropathy |
|
Mild
|
|
Moderate to Severe
|
|
| Anorexia and
Fatigue |
|
| Seizures |
|
| 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
|
|
| Renal
|
| Serum Creatinine
1.6-3.75 mg/dl |
|
| BUN
|
|
25-40 mg%
|
|
41-60 mg%
|
|
>60 mg%
|
|
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
(6-12 mg/kg/day). In general, adverse
reaction experiences were
similar in the two trails described above. Additional toxicities, not
reported in the above table, included hepatic
toxicity, skin
rash, pruritus
and alopecia, each occurring in <1% of patients.
DRUG INTERACTIONS
Concurrent administration
of HEXALEN and antidepressants of the MAO inhibitor class
may cause severe orthostatic
hypotension (see WARNINGS
section).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 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 and/or cisplatin.1
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