 |
The
safety data presented here are from the combined results
of 3 trials with a total of 80 adults with type 1 Gaucher
disease.1,2
Important Safety Information |
| Peripheral neuropathy
has been reported in patients treated with Zavesca. |
- Patients should undergo neurological
examination at the start of treatment and every 6 months
thereafter; Zavesca should be reassessed in patients who
develop symptoms of peripheral neuropathy
Zavesca may cause fetal harm if administered
to a pregnant woman. |
- Pregnancy category
X; Zavesca is contraindicated in women who are or who may become
pregnant; patients should be apprised of the potential hazard
to a fetus
There is a risk of impaired fertility
in men.
|
- Men should maintain reliable contraceptive
methods and not plan to conceive while taking Zavesca and
for 3 months thereafter
Adverse Reactions |
Two
patients withdrew from the Zavesca trials because of neuropathy
and/or neuritis.2
Mild-to-moderate tremor was reported in approximately 30% of patients in all
Zavesca trials combined.1,2 |
- Many cases resolved spontaneously within
1 to 3 months2; dose reduction
may ameliorate tremor within days1;
3 patients claimed tremor as one of the reasons for withdrawal
from the clinical trials, although 1 of these was considered
unrelated to Zavesca2
The most common adverse reactions
in all Zavesca trials combined were diarrhea (85%) and
weight loss (65%).1 |
- Diarrhea was mild-to-moderate2;
incidence decreased over time1;
managed with anti-diarrheal medications (eg, loperamide hydrochloride)
and/or dietary changes1; 6
patients who withdrew from the clinical trials claimed diarrhea
either as the main reason for withdrawal or as a contributing
factor1
- Weight loss was mild (6%–7% of
total body weight)2; most
prevalent in the first year of treatment and stabilized thereafter1,2;
no patients claimed weight loss as a reason for withdrawal
from the clinical trials2
Zavesca has not been evaluated in
patients over 65 or under 18 years of age.1
Recommendations for Patients With Renal Impairment |
| The major
route of miglustat excretion is renal1;
therefore the following dose reductions are recommended: |
- Patients with mild renal impairment
(adjusted creatinine clearance 50–70 mL/min/1.73 m2)
start at 100 mg bid1
- Patients with moderate renal impairment
(adjusted creatinine clearance 30–50 mL/min/1.73 m2)
start at 100 mg daily1
- Patients with severe renal impairment
(adjusted creatinine clearance <30 mL/min/1.73 m2) should
not receive Zavesca1
Drug-Drug Interactions |
| Miglustat
does not inhibit or induce various substrates of cytochrome
P450 enzymes.1 |
- Interactions are unlikely with drugs
that are substrates of cytochrome P450 enzymes1
In one study Zavesca increased the
clearance of Cerezyme by 70%, although these results are
inconclusive due to the small number of subjects studied
and because patients took variable doses of Cerezyme.1
Patient Alerts |
- Patients must be given the patient
information to read
- Patients must be instructed to tell
their doctor immediately if they experience any symptoms
of peripheral neuropathy (eg, numbness, tingling, or burning
in their hands, arms, legs, or feet) or tremor
|
1. Zavesca® (miglustat)
package insert. Actelion Ltd. 2003.
2. Data on file, Actelion Pharmaceuticals US, Inc.
|
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