zemplar
Generic Name: (
paricalcitol)
Dosage Type: injection, solution Organization: Abbott Laboratories
DESCRIPTION
Paricalcitol, USP, the active ingredient in Zemplar
Injection, is a synthetically manufactured analog of calcitriol, the metabolically
active form of vitamin D indicated for the prevention and treatment of secondary
hyperparathyroidism associated with chronic kidney disease(CKD) Stage 5.
Zemplar is available as a sterile, clear, colorless, aqueous solution for
intravenous injection. Each mL contains paricalcitol, 2 mcg or 5 mcg; propylene
glycol, 30% (v/v); and alcohol, 20% (v/v).
Paricalcitol
is a white powder chemically designated as 19-nor-1a,3ß,25-trihydroxy-9,10-secoergosta-5(Z),7(E),22(E)-triene
and has the following structural formula:
Molecular formula is C27H44O3.
Molecular weight is 416.64.
CLINICAL PHARMACOLOGY
Secondary hyperparathyroidism is characterized by
an elevation in parathyroid hormone (PTH) associated with inadequate levels
of active vitamin D hormone. The source of vitamin D in the body is from
synthesis in the skin and from dietary intake. Vitamin D requires two sequential
hydroxylations in the liver and the kidney to bind to and to activate the
vitamin D receptor (VDR). The endogenous VDR activator, calcitriol [1,25(OH)2 D3],
is a hormone that binds to VDRs that are present in the parathyroid gland,
intestine, kidney, and bone to maintain parathyroid function and calcium and
phosphorus homeostasis, and to VDRs found in many other tissues, including
prostate, endothelium and immune cells. VDR activation is essential for the
proper formation and maintenance of normal bone. In the diseased kidney,
the activation of vitamin D is diminished, resulting in a rise of PTH, subsequently
leading to secondary hyperparathyroidism, and disturbances in the calcium
and phosphorus homeostasis.1 The decreased levels of 1,25(OH)2 D3
and resultant elevated PTH levels, both of which often precede abnormalities
in serum calcium and phosphorus, affect bone turnover rate and may result
in renal osteodystrophy.
Mechanism of Action
Paricalcitol is a synthetic, biologically active
vitamin D analog of calcitriol with modifications to the side chain (D2)
and the A (19-nor) ring. Preclinical and in
vitro studies have demonstrated that paricalcitol's biological
actions are mediated through binding of the VDR, which results in the selective
activation of vitamin D responsive pathways. Vitamin D and paricalcitol have
been shown to reduce parathyroid hormone levels by inhibiting PTH synthesis
and secretion.
Pharmacokinetics
Within two hours after administering Zemplar intravenous
doses ranging from 0.04 to 0.24 mcg/kg, concentrations of paricalcitol decreased
rapidly; thereafter, concentrations of paricalcitol declined log-linearly.
No accumulation of paricalcitol was observed with multiple dosing.
Distribution
Paricalcitol is extensively bound to plasma proteins
(=99.8%). In healthy subjects, the steady state volume of distribution
is approximately 23.8 L. The mean apparent volume of distribution following
a 0.24 mcg/kg dose of paricalcitol in CKD Stage 5 subjects requiring hemodialysis
(HD) and peritoneal dialysis (PD) is between 31 and 35 L.
Metabolism
After IV administration of a 0.48 mcg/kg dose
of 3H-paricalcitol, parent drug was extensively metabolized, with
only about 2% of the dose eliminated unchanged in the feces and no parent
drug found in the urine. Several metabolites were detected in both the urine
and feces. Most of the systemic exposure was from the parent drug. Two
minor metabolites, relative to paricalcitol, were detected in human plasma.
One metabolite was identified as 24(R)-hydroxy paricalcitol, while the other
metabolite was unidentified. The 24(R)-hydroxy paricalcitol is less active
than paricalcitol in an in vivo rat
model of PTH suppression.
In vitro data suggest that paricalcitol is metabolized
by multiple hepatic and non-hepatic enzymes, including mitochondrial CYP24,
as well as CYP3A4 and UGT1A4. The identified metabolites include the product
of 24(R)-hydroxylation (present at low levels in plasma), as well as 24,26-
and 24,28-dihydroxylation and direct glucuronidation.
Elimination
Paricalcitol is excreted primarily by hepatobiliary
excretion. Approximately 63% of the radioactivity was eliminated in the feces
and 19% was recovered in the urine in healthy subjects. In healthy subjects,
the mean elimination half-life of paricalcitol is about five to seven hours
over the studied dose range of 0.04 to 0.16 mcg/kg. The pharmacokinetics
of paricalcitol has been studied in CKD Stage 5 subjects requiring hemodialysis
(HD) and peritoneal dialysis (PD). The mean elimination half-life of paricalcitol
after administration of 0.24 mcg/kg paricalcitol IV bolus dose in CKD Stage
5 HD and PD patients is 13.9 and 15.4 hours, respectively (Table 1).
Table 1 Mean ± SD
Paricalcitol Pharmacokinetic Parameters in CKD Stage 5 Subjects Following
Single 0.24 mcg/kg IV Bolus Dose
|
|
CKD Stage 5-HD
(n=14) |
CKD Stage 5-PD
(n=8) |
|
† harmonic mean± pseudo standard deviation, HD: hemodialysis, PD: peritoneal dialysis
|
| Cmax (ng/mL) |
1.680 ± 0.511 |
1.832 ± 0.315 |
| AUC0-8 (ng·h/mL) |
14.51 ± 4.12 |
16.01 ± 5.98 |
| ß (1/h) |
0.050 ± 0.023 |
0.045 ± 0.026 |
| t1/2 (h) † |
13.9 ± 7.3 |
15.4 ± 10.5 |
| CL (L/h) |
1.49 ± 0.60 |
1.54 ± 0.95 |
| Vdß (L) |
30.8 ± 7.5 |
34.9 ± 9.5 |
The degree of accumulation was consistent with
the half-life and dosing frequency.
Special Populations
Geriatric
The pharmacokinetics of paricalcitol have not
been investigated in geriatric patients greater than 65 years.
Pediatrics
The pharmacokinetics of paricalcitol have not
been investigated in patients less than 18 years of age.
Gender
The pharmacokinetics of paricalcitol were gender
independent.
Hepatic Impairment
The disposition of paricalcitol (0.24 mcg/kg)
was compared in patients with mild (n=5) and moderate (n=5) hepatic impairment
(as indicated by the Child-Pugh method) and subjects with normal hepatic function
(n=10). The pharmacokinetics of unbound paricalcitol were similar across
the range of hepatic function evaluated in this study. No dosing adjustment
is required in patients with mild and moderate hepatic impairment. The influence
of severe hepatic impairment on the pharmacokinetics of paricalcitol has not
been evaluated.
Renal Impairment
The pharmacokinetics of paricalcitol have been
studied in CKD Stage 5 subjects requiring hemodialysis (HD) and peritoneal
dialysis (PD). Hemodialysis procedure has essentially no effect on paricalcitol
elimination. However, compared to healthy subjects, CKD Stage 5 subjects
showed a decreased CL and increased half-life (see Pharmacokinetics- Elimination).
Drug Interactions
An in vitro study
indicates that paricalcitol is not an inhibitor of CYP1A2, CYP2A6, CYP2B6,
CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A at concentrations up to
50 nM (21 ng/mL) (approximately 20-fold greater than that obtained after highest
tested dose). In fresh primary cultured hepatocytes, the induction observed
at paricalcitol concentrations up to 50 nM was less than two-fold for CYP2B6,
CYP2C9 or CYP3A, where the positive controls rendered a six- to nineteen-fold
induction. Hence, paricalcitol is not expected to inhibit or induce the clearance
of drugs metabolized by these enzymes.
Drug
interactions with paricalcitol injection have not been studied.
Omeprazole
The pharmacokinetic interaction between paricalcitol
capsule (16 mcg) and omeprazole (40 mg; oral) was investigated in a single
dose, crossover study in healthy subjects. The pharmacokinetics of paricalcitol
were unaffected when omeprazole was administrated approximately 2 hours prior
to the paricalcitol dose.
Ketoconazole
Although no data are available for the drug interaction
between paricalcitol injection and ketoconazole, the effect of multiple doses
of ketoconazole administered as 200 mg BID for 5 days on the pharmacokinetics
of paricalcitol capsule has been studied in healthy subjects. The Cmax of
paricalcitol was minimally affected, but AUC0-8 approximately
doubled in the presence of ketoconazole. The mean half-life of paricalcitol
was 17.0 hours in the presence of ketoconazole as compared to 9.8 hours, when
paricalcitol was administered alone (See PRECAUTIONS).
CLINICAL STUDIES
In three 12-week, placebo-controlled, phase 3 studies
in chronic kidney disease Stage 5 patients on dialysis, the dose of Zemplar
was started at 0.04 mcg/kg 3 times per week. The dose was increased by 0.04 mcg/kg
every 2 weeks until intact parathyroid hormone (iPTH) levels were decreased
at least 30% from baseline or a fifth escalation brought the dose to 0.24 mcg/kg,
or iPTH fell to less than 100 pg/mL, or the Ca × P product was greater
than 75 within any 2 week period, or serum calcium became greater than 11.5
mg/dL at any time.
Patients treated with Zemplar
achieved a mean iPTH reduction of 30% within 6 weeks. In these studies, there
was no significant difference in the incidence of hypercalcemia or hyperphosphatemia
between Zemplar and placebo-treated patients. The results from these studies
are as follows:
|
|
Group
(No. of Pts.) |
Baseline Mean
(Range) |
Mean (SE) Change From
Baseline to Final Evaluation |
| PTH (pg/mL) |
Zemplar (n = 40) |
783 (291 – 2076) |
-379 (43.7) |
|
|
placebo (n = 38) |
745 (320 –1671) |
-69.6 (44.8) |
| Alkaline |
Zemplar (n = 31) |
150 (40 – 600) |
-41.5 (10.6) |
| Phosphatase (U/L) |
placebo (n = 34) |
169 (56 – 911) |
+2.6 (10.1) |
| Calcium (mg/dL) |
Zemplar (n = 40) |
9.3 (7.2 – 10.4) |
+0.47 (0.1) |
|
|
placebo (n = 38) |
9.1 (7.8 – 10.7) |
+0.02 (0.1) |
| Phosphorus (mg/dL) |
Zemplar (n = 40) |
5.8 (3.7 – 10.2) |
+0.47 (0.3) |
|
|
placebo (n = 38) |
6.0 (2.8 – 8.8) |
-0.47 (0.3) |
| Calcium × |
Zemplar (n = 40) |
54 (32 – 106) |
+7.9 (2.2) |
| Phosphorus Product |
placebo (n = 38) |
54 (26 – 77) |
-3.9 (2.3) |
A long-term, open-label safety study of 164 CKD
Stage 5 patients (mean dose of 7.5 mcg three times per week), demonstrated
that mean serum Ca, P, and Ca × P remained within clinically appropriate
ranges with PTH reduction (mean decrease of 319 pg/mL at 13 months).
INDICATIONS AND USAGE
Zemplar is indicated for the prevention and treatment
of secondary hyperparathyroidism associated with chronic kidney disease Stage
5.
CONTRAINDICATIONS
Zemplar should not be given to patients with evidence
of vitamin D toxicity, hypercalcemia, or hypersensitivity to any ingredient
in this product (see WARNINGS).
WARNINGS
Acute overdose of Zemplar may cause hypercalcemia,
and require emergency attention. During dose adjustment, serum calcium and
phosphorus levels should be monitored closely (e.g., twice weekly). If clinically
significant hypercalcemia develops, the dose should be reduced or interrupted.
Chronic administration of Zemplar may place patients at risk of hypercalcemia,
elevated Ca × P product, and metastatic calcification.
Treatment of patients with clinically significant hypercalcemia
consists of immediate dose reduction or interruption of Zemplar therapy and
includes a low calcium diet, withdrawal of calcium supplements, patient mobilization,
attention to fluid and electrolyte imbalances, assessment of electrocardiographic
abnormalities (critical in patients receiving digitalis), hemodialysis or
peritoneal dialysis against a calcium-free dialysate, as warranted. Serum
calcium levels should be monitored frequently until normocalcemia ensues.
Phosphate or vitamin D-related compounds should not be taken
concomitantly with Zemplar.
PRECAUTIONS
General
Digitalis toxicity is potentiated by hypercalcemia
of any cause, so caution should be applied when digitalis compounds are prescribed
concomitantly with Zemplar. Adynamic bone lesions may develop if PTH levels
are suppressed to abnormal levels.
Information for the Patient
The patient should be instructed that, to ensure
effectiveness of Zemplar therapy, it is important to adhere to a dietary regimen
of calcium supplementation and phosphorus restriction. Appropriate types
of phosphate-binding compounds may be needed to control serum phosphorus levels
in patients with chronic kidney disease (CKD) Stage 5, but excessive use of
aluminum containing compounds should be avoided. Patients should also be
carefully informed about the symptoms of elevated calcium (see ADVERSE
REACTIONS).
Laboratory Tests
During the initial phase of medication, serum calcium
and phosphorus should be determined frequently (e.g., twice weekly). Once
dosage has been established, serum calcium and phosphorus should be measured
at least monthly. Measurements of serum or plasma PTH are recommended every
3 months. An intact PTH (iPTH) assay is recommended for reliable detection
of biologically active PTH in patients with CKD Stage 5. During dose adjustment
of Zemplar, laboratory tests may be required more frequently.
Drug Interactions
Paricalcitol is not expected to inhibit the clearance
of drugs metabolized by cytochrome P450 enzymes CYP1A2, CYP2A6, CYP2B6, CYP2C8,
CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A nor induce the clearance of drug
metabolized by CYP2B6, CYP2C9 or CYP3A.
Specific
interaction studies were not performed with Zemplar Injection.
A multiple dose drug-drug interaction study with ketoconazole
and paricalcitol capsule demonstrated that ketoconazole approximately doubled
paricalcitol AUC0-8 (see CLINICAL
PHARMACOLOGY). Since paricalcitol is partially metabolized by CYP3A
and ketoconazole is known to be a strong inhibitor of cytochrome P450 3A enzyme,
care should be taken while dosing paricalcitol with ketoconazole and other
strong P450 3A inhibitors including atazanavir, clarithromycin, indinavir,
itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin
or voriconazole.
Digitalis toxicity is potentiated
by hypercalcemia of any cause, so caution should be applied when digitalis
compounds are prescribed concomitantly with Zemplar.
Carcinogenesis, Mutagenesis, Impairment of Fertility
In a 104-week carcinogenicity study in CD-1 mice,
an increased incidence of uterine leiomyoma and leiomyosarcoma was observed
at subcutaneous doses of 1, 3, 10 mcg/kg (2 to 15 times the AUC at a human
dose of 14 mcg, equivalent to 0.24 mcg/kg based on AUC). The incidence rate
of uterine leiomyoma was significantly different than the control group at
the highest dose of 10 mcg/kg.
In a 104-week
carcinogenicity study in rats, there was an increased incidence of benign
adrenal pheochromocytoma at subcutaneous doses of 0.15, 0.5, 1.5 mcg/kg (<
1 to 7 times the exposure following a human dose of 14 mcg, equivalent to
0.24 mcg/kg based on AUC). The increased incidence of pheochromocytomas in
rats may be related to the alteration of calcium homeostasis by paricalcitol.
Paricalcitol did not exhibit genetic toxicity in
vitro with or without metabolic activation in the microbial mutagenesis
assay (Ames Assay), mouse lymphoma mutagenesis assay (L5178Y), or a human
lymphocyte cell chromosomal aberration assay. There was also no evidence
of genetic toxicity in an in vivo mouse
micronucleus assay. Zemplar had no effect on fertility (male or female) in
rats at intravenous doses up to 20 mcg/kg/dose [equivalent to 13 times the
highest recommended human dose (0.24 mcg/kg) based on surface area, mg/m2].
Pregnancy
Pregnancy Category C
Paricalcitol has been shown to cause minimal decreases
in fetal viability (5%) when administered daily to rabbits at a dose 0.5 times
the 0.24 mcg/kg human dose (based on surface area, mg/m2) and when
administered to rats at a dose 2 times the 0.24 mcg/kg human dose (based
on plasma levels of exposure). At the highest dose tested (20 mcg/kg
3 times per week in rats, 13 times the 0.24 mcg/kg human dose based on surface
area), there was a significant increase of the mortality of newborn rats at
doses that were maternally toxic (hypercalcemia). No other effects on offspring
development were observed. Paricalcitol was not teratogenic at the doses
tested.
There are no adequate and well-controlled
studies in pregnant women. Zemplar should be used during pregnancy only if
the potential benefit to the mother justifies the potential risk to the fetus.
Nursing Mothers
Studies in rats have shown that paricalcitol is
present in the milk. It is not known whether paricalcitol is excreted in
human milk. In the nursing patient, a decision should be made whether to discontinue
nursing or to discontinue the drug, taking into account the importance of
the drug to the mother.
Pediatric Use
The safety and effectiveness of Zemplar were examined
in a 12-week randomized, double-blind, placebo-controlled study of 29 pediatric
patients, aged 5-19 years, with end-stage renal disease on hemodialysis and
nearly all had received some form of vitamin D prior to the study. Seventy-six
percent of the patients were male, 52% were Caucasian and 45% were African-American.
The initial dose of Zemplar was 0.04 mcg/kg 3 times per week based on baseline
iPTH level of less than 500 pg/mL, or 0.08 mcg/kg 3 times a week, based on
baseline iPTH level of = 500 pg/mL, respectively. The dose of Zemplar
was adjusted in 0.04 mcg/kg increments based on the levels of serum iPTH,
calcium and Ca x P. The mean baseline levels of iPTH were 841 pg/mL for the
15 Zemplar-treated patients and 740 pg/mL for the 14 placebo-treated subjects.
The mean dose of Zemplar administered was 4.6 mcg (range: 0.8 mcg –
9.6 mcg). Ten of the 15 (67%) Zemplar-treated patients and 2 of the 14 (14%)
placebo-treated patients completed the trial. Ten of the placebo patients
(71%) were discontinued due to excessive elevations in iPTH levels as defined
by 2 consecutive iPTH levels > 700 pg/mL and greater than baseline after 4
weeks of treatment.
In the primary efficacy
analysis, 9 of 15 (60%) subjects in the Zemplar group had 2 consecutive 30%
decreases from baseline iPTH compared with 3 of 14 (21%) patients in the placebo
group (95% CI for the difference between groups –1%, 63%). Twenty-three
percent of Zemplar vs. 31% of placebo patients had at least one serum calcium
level > 10.3 mg/dL, and 40% vs. 14% of Zemplar vs. placebo subjects had at
least one Ca x P ion product > 72 (mg/dL)2. The overall percentage
of serum calcium measurements > 10.3 mg/dL was 7% in the Zemplar group and
7% in the placebo group; the overall percentage of patients with Ca x P product
> 72 (mg/dL)2 was 8% in the Zemplar group and 7% in the placebo
group. No subjects in either the Zemplar group or placebo group developed
hypercalcemia (defined as at least one calcium value > 11.2 mg/dL) during
the study.
Geriatric Use
Of the 40 patients receiving Zemplar in the three
phase 3 placebo-controlled CKD Stage 5 studies, 10 patients were 65 years
or over. In these studies, no overall differences in efficacy or safety were
observed between patients 65 years or older and younger patients.
ADVERSE REACTIONS
Zemplar has been evaluated for safety in clinical
studies in 454 CKD Stage 5 patients. In four, placebo-controlled, double-blind,
multicenter studies, discontinuation of therapy due to any adverse event occurred
in 6.5% of 62 patients treated with Zemplar (dosage titrated as tolerated,
see CLINICAL PHARMACOLOGY - Clinical Studies)
and 2.0% of 51 patients treated with placebo for 1 to 3 months. Adverse
events occurring with greater frequency in the Zemplar group at a frequency
of 2% or greater, regardless of causality, are presented in the following
table:
Adverse
Event Incidence Rates for All Treated Patients In All Placebo-Controlled Studies
| Adverse Event |
Zemplar (n = 62)
% |
Placebo (n = 51)
% |
| Overall |
71 |
78 |
| Body as a Whole |
|
|
| Chills |
5 |
0 |
| Feeling unwell |
3 |
0 |
| Fever |
5 |
2 |
| Flu |
5 |
4 |
| Sepsis |
5 |
2 |
| Cardiovascular System |
|
|
| Palpitation |
3 |
0 |
| Digestive System |
|
|
| Dry mouth |
3 |
2 |
| Gastrointestinal bleeding |
5 |
2 |
| Nausea |
13 |
8 |
| Vomiting |
8 |
4 |
| Metabolic and Nutritional Disorders |
|
|
| Edema |
7 |
0 |
| Nervous System |
|
|
| Light-headedness |
5 |
2 |
| Respiratory System |
|
|
| Pneumonia |
5 |
0 |
A patient who reported the same medical term more
than once was counted only once for that medical term.
Safety
parameters (changes in mean Ca, P, Ca × P) in an open-label safety study
up to 13 months in duration support the long-term safety of Zemplar in
this patient population.
Potential adverse events
of Zemplar Injection are, in general, similar to those encountered with excessive
vitamin D intake. Signs and symptoms of vitamin D intoxication associated
with hypercalcemia include:
Early
Weakness, headache, somnolence, nausea, vomiting,
dry mouth, constipation, muscle pain, bone pain, and metallic taste.
Late
Anorexia, weight loss, conjunctivitis (calcific),
pancreatitis, photophobia, rhinorrhea, pruritus, hyperthermia, decreased libido,
elevated BUN, hypercholesterolemia, elevated AST and ALT, ectopic calcification,
hypertension, cardiac arrhythmias, somnolence, death, and rarely, overt psychosis.
Adverse Events During Post-marketing Experience
Taste perversion, such as metallic taste, and allergic
reactions, such as rash, urticaria, pruritus, facial and oral edema rarely
have been reported.
OVERDOSAGE
Overdosage of Zemplar may lead to hypercalcemia, hypercalciuria,
hyperphosphatemia, and over suppression of PTH. (see WARNINGS).
Treatment of Overdosage and Hypercalcemia
The treatment of acute overdosage should consist
of general supportive measures. Serial serum electrolyte determinations (especially
calcium), rate of urinary calcium excretion, and assessment of electrocardiographic
abnormalities due to hypercalcemia should be obtained. Such monitoring is
critical in patients receiving digitalis. Discontinuation of supplemental
calcium and institution of a low calcium diet are also indicated in acute
overdosage.
General treatment of hypercalcemia
due to overdosage consists of immediate suspension of Zemplar therapy, institution
of a low calcium diet, and withdrawal of calcium supplements. Serum calcium
levels should be determined at least weekly until normocalcemia ensues. When
serum calcium levels have returned to within normal limits, Zemplar may be
reinitiated at a lower dose. If persistent and markedly elevated serum calcium
levels occur, there are a variety of therapeutic alternatives that may be
considered. These include the use of drugs such as phosphates and corticosteroids
as well as measures to induce diuresis. Also, one may consider dialysis against
a calcium-free dialysate.
DOSAGE AND ADMINISTRATION
The currently accepted target range for iPTH levels
in CKD Stage 5 patients is no more than 1.5 to 3 times the non-uremic
upper limit of normal.
The recommended initial
dose of Zemplar is 0.04 mcg/kg to 0.1 mcg/kg (2.8 – 7 mcg) administered
as a bolus dose no more frequently than every other day at any time during
dialysis.
If a satisfactory response is not observed,
the dose may be increased by 2 to 4 mcg at 2- to 4-week intervals. During
any dose adjustment period, serum calcium and phosphorus levels should be
monitored more frequently, and if an elevated calcium level or a Ca ×
P product greater than 75 is noted, the drug dosage should be immediately
reduced or interrupted until these parameters are normalized. Then, Zemplar
should be reinitiated at a lower dose. If a patient is on a calcium-based
phosphate binder, the dose may be decreased or withheld, or the patient may
be switched to a non-calcium-based phosphate binder. Zemplar doses may need
to be decreased as the PTH levels decrease in response to therapy. Thus,
incremental dosing must be individualized.
The
following table is a suggested approach in dose titration:
Suggested Dosing Guidelines
| PTH Level |
Zemplar Dose |
| the same or increasing |
increase |
| decreasing by < 30% |
increase |
| decreasing by > 30%, < 60% |
maintain |
| decreasing by > 60% |
decrease |
| one and one-half to three times upper limit of normal |
maintain |
The influence of mild to moderately impaired hepatic
function on paricalcitol pharmacokinetics is sufficiently small that no dosing
adjustment is required.
Parenteral drug products
should be inspected visually for particulate matter and discoloration prior
to administration whenever solution and container permit.
Discard unused portion.
HOW SUPPLIED
Zemplar Injection is available as 2 mcg/mL (NDC 0074-4637-01) and 5 mcg/mL (NDC 0074-1658-01 and NDC 0074-1658-02).
| List No. |
Volume/Container |
Concentration |
Total Content |
| 4637-01 |
1 mL/Fliptop Vial |
2 mcg/mL |
2 mcg |
| 1658-01 |
1 mL/Fliptop Vial |
5 mcg/mL |
5 mcg |
| 1658-02 |
2 mL/Fliptop Vial |
5 mcg/mL |
10 mcg |
Store at 25°C (77°F). Excursions permitted
between 15° - 30°C (59° - 86°F).
U.S.
patents: 5,246,925; 5,587,497; 6,136,799; 6,361,758
REFERENCES
- K/DOQI Clinical Practice Guidelines for Bone Metabolism and Disease
in Chronic Kidney Disease. Am J Kidney Dis 2003; Volume 42(4): Supplement
3.
© Abbott 2005
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by
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IL 60045 USA
For
Abbott
Laboratories
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Revised: 06/2006Abbott Laboratories