Pamidronate
Aredia ® |
| Usual
Diluents |
| NS,
D5W |
| Standard
Dilutions [Amount of drug]
[Infusion volume] [Infusion rate] |
[60-90
mg] [1000 ml] [24 hours]
Minimum dilution:
[60-90mg] [500ml] [Usually over 4 hours] (Range: 2
to 24 hr) |
|
| Stability
/ Miscellaneous |
Restricted
to oncology. Serum calcium levels
should be corrected for serum albumin before
determining dose.
Corrected calcium= serum calcium + 0.8 (4 - serum
albumin).
Dosage:
Moderate hypercalcemia (12- 13.5 mg/dl): 60 to 90
mg. Severe hypercalcemia (> 13.5 mg/dl): 90 mg.
The manufacturer recommends that the repeat dose
not be given sooner than 7 days after the initial
dose in order to allow full response to this dose.
Mechanism of action: biphosphonate
compound-inhibits bone resorption (anti-osteoclast
activity). Has little effect on bone
remineralization.
Relative potency of biphosphonate agents:
Risedronate (Actonel)>> (pamidronate &
alendronate (Fosamax)) >>Etidronate(Didronel)
DOSAGE AND ADMINISTRATION
Hypercalcemia of Malignancy
Consideration should be given to the severity of
as well as the symptoms of hypercalcemia. Vigorous
saline hydration alone may be sufficient for
treating mild, asymptomatic hypercalcemia.
Overhydration should be avoided in patients who
have potential for cardiac failure. In
hypercalcemia associated with hematologic
malignancies, the use of glucocorticoid therapy
may be helpful.
Moderate Hypercalcemia
The recommended dose of Aredia in moderate
hypercalcemia (corrected serum calcium* of
approximately 12-13.5 mg/dL) is 60 to 90 mg given
as a SINGLE-DOSE, intravenous infusion over 2 to
24 hours. Longer infusions (i.e., >2 hours) may
reduce the risk for renal toxicity, particularly
in patients with preexisting renal insufficiency.
Severe Hypercalcemia
The recommended dose of Aredia in severe
hypercalcemia (corrected serum calcium*>13.5
mg/dL) is 90 mg given as a SINGLE-DOSE,
intravenous infusion over 2 to 24 hours. Longer
infusions (i.e., >2 hours) may reduce the risk
for renal toxicity, particularly in patients with
preexisting renal insufficiency.
___________________________
*Albumin-corrected serum calcium (CCa,mg/dL) =
serum calcium, mg/dL + 0.8 (4.0-serum albumin, g/dL).
Retreatment
A limited number of patients have received more
than one treatment with Aredia for hypercalcemia.
Retreatment with Aredia, in patients who show
complete or partial response initially, may be
carried out if serum calcium does not return to
normal or remain normal after initial treatment.
It is recommended that a minimum of 7 days elapse
before retreatment, to allow for full response to
the initial dose. The dose and manner of
retreatment is identical to that of the initial
therapy.
Paget’s Disease
The recommended dose of Aredia in patients with
moderate to severe Paget’s disease of bone is 30
mg daily, administered as a 4-hour infusion on 3
consecutive days for a total dose of 90 mg.
Retreatment
A limited number of patients with Paget’s
disease have received more than one treatment of
Aredia in clinical trials. When clinically
indicated, patients should be retreated at the
dose of initial therapy.
Osteolytic Bone Lesions of Multiple Myeloma
The recommended dose of Aredia in patients with
osteolytic bone lesions of multiple myeloma is 90
mg administered as a 4-hour infusion given on a
monthly basis.
Patients with marked Bence-Jones proteinuria and
dehydration should receive adequate hydration
prior to Aredia infusion.
Limited information is available on the use of
Aredia in multiple myeloma patients with a serum
creatinine ≥3.0 mg/dL.
Patients who receive Aredia should have serum
creatinine assessed prior to each treatment.
Treatment should be withheld for renal
deterioration. In a clinical study, renal
deterioration was defined as follows:
• For patients with normal baseline creatinine,
increase of 0.5 mg/dL.
• For patients with abnormal baseline creatinine,
increase of 1.0 mg/dL.
In this clinical study, Aredia treatment was
resumed only when the creatinine returned to
within 10% of the baseline value.
The optimal duration of therapy is not yet known,
however, in a study of patients with myeloma,
final analysis after 21 months demonstrated
overall benefits (see package insert CLINICAL
TRIALS section).
Osteolytic Bone Metastases of Breast Cancer
The recommended dose of Aredia in patients with
osteolytic bone metastases is 90 mg administered
over a 2-hour infusion given every 3-4 weeks.
Aredia has been frequently used with doxorubicin,
fluorouracil, cyclophosphamide, methotrexate,
mitoxantrone, vinblastine, dexamethasone,
prednisone, melphalan, vincristine, megesterol,
and tamoxifen. It has been given less frequently
with etoposide, cisplatin, cytarabine, paclitaxel,
and aminoglutethimide.
Patients who receive Aredia should have serum
creatinine assessed prior to each treatment.
Treatment should be withheld for renal
deterioration. In a clinical study, renal
deterioration was defined as follows:
• For patients with normal baseline creatinine,
increase of 0.5 mg/dL.
• For patients with abnormal baseline creatinine,
increase of 1.0 mg/dL.
In this clinical study, Aredia treatment was
resumed only when the creatinine returned to
within 10% of the baseline value.
The optimal duration of therapy is not known,
however, in two breast cancer studies, final
analyses performed after 24 months of therapy
demonstrated overall benefits (see package insert
CLINICAL TRIALS section).
Calcium and Vitamin D
Supplementation
In the absence of hypercalcemia, patients with
predominantly lytic bone metastases or multiple
myeloma, who are at risk of calcium or vitamin D
deficiency, and patients with Paget’s disease of
the bone, should be given oral calcium and vitamin
D supplementation in order to minimize the risk of
hypocalcemia.
--------------Preparation
of Solution------------------------------
Reconstitution
Aredia is reconstituted by adding 10 mL of Sterile
Water for Injection, USP, to each vial, resulting
in a solution of 30 mg/10 mL or 90 mg/10 mL. The
pH of the reconstituted solution is 6.0-7.4. The
drug should be completely dissolved before the
solution is withdrawn.
Method of Administration
DUE TO THE RISK OF CLINICALLY SIGNIFICANT
DETERIORATION IN RENAL FUNCTION, WHICH MAY
PROGRESS TO RENAL FAILURE, SINGLE DOSES OF AREDIA
SHOULD NOT EXCEED 90 MG. (SEE package insert for
WARNINGS.)
There must be strict adherence to the intravenous
administration recommendations for Aredia in order
to decrease the risk of deterioration in renal
function.
Hypercalcemia of Malignancy
The daily dose must be administered as an
intravenous infusion over at least 2 to 24 hours
for the 60-mg and 90-mg doses. The recommended
dose should be diluted in 1000 mL of sterile 0.45%
or 0.9% Sodium Chloride, USP, or 5% Dextrose
Injection, USP. This infusion solution is stable
for up to 24 hours at room temperature.
Paget’s Disease
The recommended daily dose of 30 mg should be
diluted in 500 mL of sterile 0.45% or 0.9% Sodium
Chloride, USP, or 5% Dextrose Injection, USP, and
administered over a 4-hour period for 3
consecutive days.
Osteolytic Bone Metastases of Breast Cancer
The recommended dose of 90 mg should be diluted in
250 mL of sterile 0.45% or 0.9% Sodium Chloride,
USP, or 5% Dextrose Injection, USP, and
administered over a 2-hour period every 3-4 weeks.
Osteolytic Bone Lesions of Multiple Myeloma
The recommended dose of 90 mg should be diluted in
500 mL of sterile 0.45% or 0.9% Sodium Chloride,
USP, or 5% Dextrose Injection, USP, and
administered over a 4-hour period on a monthly
basis.
Aredia must not be mixed with calcium-containing
infusion solutions, such as Ringer’s solution,
and should be given in a single intravenous
solution and line separate from all other drugs.
Note: Parenteral drug products should be inspected
visually for particulate matter and discoloration
prior to administration, whenever solution and
container permit.
Aredia reconstituted with Sterile Water for
Injection may be stored under refrigeration at 2°C-8°C
(36°F-46°F) for up to 24 hours.
HOW SUPPLIED
Vials - 30 mg - each contains 30 mg of sterile,
lyophilized pamidronate disodium and 470 mg of
mannitol, USP. Carton of 4 vials NDC
0078-0463-91
Vials - 90 mg - each contains 90 mg of sterile,
lyophilized pamidronate disodium and 375 mg
of mannitol, USP. Carton of 1 vial NDC
0078-0464-61
Do not store above 30°C (86°F).
T2007-98
REV: November 2007
Novartis Pharmaceuticals Corporation
East Hanover, New Jersey 07936
© Novartis |
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