WARNINGS
Paget’s Disease
In Paget’s patients the response to therapy may
be of slow onset and continue for months after Didronel
therapy is discontinued. Dosage should not be increased
prematurely. A 90-day drug-free interval should be provided
between courses of therapy.
Heterotopic Ossification
No specific warnings.
PRECAUTIONS
General
Patients should maintain an adequate nutritional status,
particularly an adequate intake of calcium and vitamin
D.
Therapy has been withheld from some patients with enterocolitis
since diarrhea may be experienced, particularly at higher
doses.
Didronel is not metabolized and is excreted intact via
the kidney. Hyperphosphatemia may occur at doses of 10
to 20 mg/kg/day, apparently as a result of drug-related
increases in tubular reabsorption of phosphate. Serum
phosphate levels generally return to normal 2 to 4 weeks
posttherapy. There is no experience to specifically guide
treatment in patients with impaired renal function. Didronel
dosage should be reduced when reductions in glomerular
filtration rates are present. Patients with renal impairment
should be closely monitored. In approximately 10% of patients
in clinical trials of Didronel I.V. infusion (etidronate
disodium) for hypercalcemia of malignancy, occasional,
mild-to-moderate abnormalities in renal function (increases
of ~0.5 mg/dl serum creatinine) were observed during or
immediately after treatment.
Didronel suppresses bone turnover, and may retard mineralization
of osteoid laid down during the bone accretion process.
These effects are dose and time dependent. Osteoid, which
may accumulate noticeably at doses of 10 to 20 mg/kg/day,
mineralizes normally posttherapy. In patients with fractures,
especially of long bones, it may be advisable to delay
or interrupt treatment until callus is evident.
Paget’s Disease
In Paget’s patients, treatment regimens exceeding
the recommended (see DOSAGE AND ADMINISTRATION) daily
maximum dose of 20 mg/kg or continuous Didronel (etidronate
disodium) administration of medication for periods greater
than 6 months may be associated with osteomalacia and
an increased risk of fracture.
Long bones predominantly affected by l.t.c lesions, particularly
in those patients unresponsive to Didronel therapy, may
be especially prone to fracture. Patients with predominantly
l.t.c lesions should be monitored radiographically and
biochemically to permit termination of Didronel in those
patients unresponsive to treatment.
Carcinogenesis
Long-term studies in rats have indicated that Didronel
is not carcinogenic.
Pregnancy
Teratogenic Effects: Pregnancy
Category C. In teratology and developmental toxicity studies
conducted in rats and rabbits treated with doses of up
to 100 mg/kg (5 to 20 times the clinical dose), no adverse
or teratogenic effects have been observed in the offspring.
Etidronate disodium has been shown to cause skeletal abnormalities
in rats when given at oral dose levels of 300 mg/kg 15
to 60 times the human dose). Other effects on the offspring
(including decreased live births) are at dosages that
cause significant toxicity in the parent generation and
are 25 to 200 times the human dose. The skeletal effects
are thought to be the result of the pharmacological effects
of the drug on the bone.
There are no adequate and well-controlled studies in
pregnant women. Didronel (etidronate disodium) should
be used during prenancy only if the potential benefit
justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether this drug is excreted in human
milk. Because many drugs are excreted in human milk, caution
should be exercised when Didronel is administered to a
nursing woman.
Pediatric Use
Safety and effectiveness in pediatric patients have not
been established. Pediatric patients have been treated
with Didronel, at doses recommended for adults, to prevent
heterotopic ossifications or soft tissue calcifications.
A rachitic syndrome has been reported infrequently at
doses of 10 mg/kg/day and more for prolonged periods approaching
or exceeding a year. The epiphyseal radiologic changes
associated with retarded mineralization of new osteoid
and cartilage, and occasional symptoms reported, have
been reversible when medication is discontinued.
Geriatric Use
Clinical studies of Didronel did not include sufficient
numbers of subjects aged 65 and over to determine whether
they respond differently from younger subjects. Other
reported clinical experience has not identified differences
in responses between elderly and younger patients. In
general, dose.selection for an elderly patient should
be cautious, reflecting the greater frequency of decreased
hepatic renal, or cardiac function, and of concomitant
disease or other drug therapy. This drug is known to be
substantially excreted by the kidney, and the risk of
toxic reactions to this drug may be greater in patients
with impaired renal function. Because elderly patients
are more likely to have decreased renal function, care
should be taken when prescribing this drug therapy. As
stated in
PRECAUTIONS
, Didronel dosage should be reduced when reductions in
glomerular filtration rates are present. In addition,
patients with renal impairment should be closely monitored.
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