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
Rocaltrol Warnings, Precautions, Pregnancy, Nursing, Abuse - Vitamin D/ Calcitriol
Rocaltrol Warnings, Precautions, Pregnancy, Nursing, Abuse - Vitamin D/ Calcitriol
WARNINGS
Overdosage of any form
of vitamin D is dangerous
(see OVERDOSAGE).
Progressive hypercalcemia
due to overdosage of vitamin
D and its metabolites may be so severe as to require emergency
attention. Chronic hypercalcemia can lead
to generalized vascular
calcification, nephrocalcinosis
and other soft-tissue calcification. The serum
calcium times phosphate
(Ca x P) product should not be allowed to exceed 70. Radiographic
evaluation of suspect anatomical regions may be useful in the early
detection of this condition.
Rocaltrol is the most potent
metabolite of vitamin
D available. The administration of Rocaltrol to patients in excess
of their daily requirements can cause
hypercalcemia,
hypercalciuria
and hyperphosphatemia. Therefore, pharmacologic doses of vitamin
D and its derivatives should be withheld during Rocaltrol treatment
to avoid possible additive
effects and hypercalcemia.
A non-aluminum phosphate-binding compound
and a low-phosphate diet
should be used to control
serum phosphorus
levels in patients undergoing dialysis.
Magnesium-containing antacids and Rocaltrol should not be used
concomitantly in patients on chronic
renal dialysis
because such use may lead
to the development of hypermagnesemia.
Studies in dogs and rats given calcitriol
for up to 26 weeks have shown that small increases of calcitriol
above endogenous
levels can lead to abnormalities
of calcium metabolism
with the potential
for calcification of many tissues in the body.
PRECAUTIONS
General
Excessive dosage of
Rocaltrol induces hypercalcemia
and in some instances hypercalciuria; therefore, early in treatment
during dosage adjustment,
serum calcium should
be determined twice weekly. In
dialysis patients,
a fall in serum
alkaline phosphatase
levels usually antedates the appearance of hypercalcemia
and may be an indication
of impending hypercalcemia. Should hypercalcemia develop, the drug
should be discontinued immediately. Rocaltrol should be given cautiously
to patients on digitalis, because hypercalcemia in such
patients may precipitate
cardiac arrhythmias.
In patients with normal
renal function, chronic
hypercalcemia
may be associated with an increase in serum
creatinine. While this is usually reversible, it is important in
such patients to pay careful
attention to those
factors which may lead
to hypercalcemia. Rocaltrol therapy
should always be started at the lowest possible dose
and should not be increased without careful monitoring of the serum
calcium. An estimate of daily
dietary calcium intake
should be made and the intake
adjusted when indicated.
Patients with normal
renal function
taking Rocaltrol should avoid dehydration. Adequate fluid
intake should be maintained.
Information for Patients
See PATIENT INFORMATION.
Laboratory Tests
For dialysis patients,
serum calcium,
phosphorus, magnesium
and alkaline phosphatase should be determined periodically. For
hypoparathyroid patients, serum calcium,
phosphorus and 24-hour
urinary calcium
should be determined periodically. For predialysis patients, serum
calcium, phosphorus,
alkaline phosphatase, creatinine
and intact PTH (iPTH) should
be determined initially. Thereafter, serum
calcium, phosphorus,
alkaline phosphatase
and creatine should be determined monthly for a 6-month period
and then determined periodically. Intact PTH
(iPTH) should be determined periodically every 3 to 4 months at
the time of visits.
Drug Interactions
See DRUG INTERACTIONS.
Carcinogenesis, Mutagenesis and Impairment of Fertility
Long-term studies in animals have not been conducted to evaluate
the carcinogenic potential
of Rocaltrol. Rocaltrol is not mutagenic in vitro in the Ames Test,
nor is it genotoxic
in vivo in the Mouse Micronucleus Test. No
significant effects
of Rocaltrol on fertility
and/or general reproductive performances were observed in a Segment
I study in rats at doses of up to 0.3 µg/kg (approximately
3 times the maximum
recommended dose based on body
surface area).
Pregnancy
Teratogenic Effects: Pregnancy Category C.
Rocaltrol has been found to be teratogenic
in rabbits when given at doses of 0.08 and 0.3 µg/kg (approximately
2 and 6 times the maximum
recommended dose based on mg/m2 ). All 15 fetuses in
3 litters at these doses showed external
and skeletal abnormalities.
However, none of the other 23 litters (156 fetuses) showed external
and skeletal abnormalities
compared with controls.
Teratogenicity studies in rats at doses up to 0.45 µg/kg
(approximately 5 times maximum
recommended dose based
on mg/m2 ) showed no evidence of teratogenic
potential. There are no adequate
and well-controlled studies in pregnant
women. Rocaltrol should be used during pregnancy
only if the potential
benefit justifies the
potential risk
to the fetus.
Nonteratogenic Effects: In
the rabbit, dosages of 0.3 mcg/kg/day (approximately 6 times maximum
recommended dose based
on surface area) administered on days 7 to 18 of gestation
resulted in 19% maternal mortality, a decrease in mean
fetal body
weight and a reduced
number of newborn surviving
to 24 hours. A study of perinatal
and postnatal development
in rats resulted in hypercalcemia
in the offspring of dams given Rocaltrol at doses of 0.08 or 0.3
mcg/kg/day (approximately 1 and 3 times the maximum recommended
dose based on mg/m2
), hypercalcemia
and hypophosphatemia in dams given Rocaltrol at a dose
of 0.08 or 0.3 mcg/kg/day, and increased serum urea
nitrogen in dams given
Rocaltrol at a dose of
0.3 mcg/kg/day. In another study in rats, maternal
weight gain
was slightly reduced at a dose
of 0.3 mcg/kg/day (approximately 3 times the maximum
recommended dose based on mg/m2 ) administered on days
72 to 15 of gestation. The offspring of a woman
administered 17 mcg/day to 36 mcg/day of Rocaltrol (approximately
17 to 36 times the maximum
recommended dose), during pregnancy manifested mild hypercalcemia
in the first 2 days of life
which returned to normal
at day 3.
Nursing Mothers
Calcitriol from ingested Rocaltrol may be excreted in human
milk. Because many drugs are excreted in human
milk and because of the
potential for serious
adverse reactions from Rocaltrol in nursing
infants, a mother should
not nurse while taking
Rocaltrol.
Pediatric Use
Safety and effectiveness
of Rocaltrol in pediatric
patients undergoing dialysis have not been established. The safety
and effectiveness
of Rocaltrol in pediatric
predialysis patients is based on evidence
from adequate and well-controlled studies of Rocaltrol in adults
with predialysis chronic renal failure
and additional supportive data from non-placebo controlled studies
in pediatric patients.
Dosing guidelines have not been established for pediatric
patients under 1 year of age
with hypoparathyroidism
or for pediatric patients less than 6 years of age
with pseudohypoparathyroidism (see DOSAGE
AND ADMINISTRATION: Hypoparathyroidism).
Oral doses of Rocaltrol ranging from 10 to 55 ng/kg/day have been
shown to improve calcium
homeostasis and
bone disease
in pediatric patients
with chronic renal failure
for whom hemodialysis
is not yet required (predialysis). Long-term calcitriol
therapy is well-tolerated
by pediatric patients.
The most common safety issues are mild, transient
episodes of hypercalcemia, hyperphosphatemia, and increases in the
serum calcium
times phosphate (Ca
x P) product which are
managed effectively by dosage
adjustment or temporary
discontinuation of the vitamin
D derivative.
Geriatric Use
Safety and effectiveness
of Rocaltrol in geriatric patients undergoing dialysis have not
been established.
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