Aredia

pamidronate disodium for injection
For Intravenous Infusion
Rx only

DESCRIPTION

Aredia, pamidronate disodium (APD), is a bone-resorption inhibitor available in 30-mg or 90-mg vials for intravenous administration

Each 30-mg, and 90-mg vial contains, respectively, 30 mg and 90 mg of sterile, lyophilized pamidronate disodium and 470 mg and 375 mg of mannitol, USP. The pH of a 1% solution of pamidronate disodium in distilled water is approximately 8.3. Aredia, a member of the group of chemical compounds known as bisphosphonates, is an analog of pyrophosphate. Pamidronate disodium is designated chemically as phosphonic acid (3-amino-1-hydroxypropylidene) bis-, disodium salt, pentahydrate, (APD), and its structuralformula is

Pamidronate disodium is a white-to-practically-white powder. It is soluble in water and in 2N sodium hydroxide, sparingly soluble in 0.1N hydrochloric acid and in 0.1N acetic acid, and practically insoluble in organic solvents. Its molecular formula is C3H9NO7P2Na2·5H2O and its molecular weight is 369.1

Inactive Ingredients. Mannitol, USP, and phosphoric acid
(for adjustment to pH 6.5 prior to lyophilization)

INDICATIONS AND USAGE

Hypercalcemia of Malignancy
Aredia, in conjunction with adequate hydration, is indicated for the treatment of moderate or severe hypercalcemia associated with malignancy, with or without bone m etastases. Patients who have either epidermoid or non-epidermoid tumors respond to treatment with Aredia. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urineoutput to about 2 L/day throughout treatment. Mild or asymptomatichypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated adequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia. The safety and efficacy of Aredia in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established

Paget’s Disease
Aredia is indicated for the treatment of patients with moderate to severe Paget’s disease of bone. The effectiveness of Aredia was demonstrated primarily in patients with serumalkalinephosphatase ³3 times the upper limit of normal. Aredia therapy in patients with Paget’s disease has been effective in reducing serumalkalinephosphatase and urinary hydroxyproline levels by ³50% in at least 50% of patients, and by ³30% in at least 80% of patients. Aredia therapy has also been effective in reducing these biochemical markers in patients with Paget’s disease who failed to respond, or no longer responded to other treatments

oseolytic Bone m etastases of Breast Cancer and Osteolytic Lesions of Multiple Myeloma
Aredia is indicated, in conjunction with standardantineoplastic therapy, for the treatment of osteolyticbone m etastases of breast cancer and osteolytic lesions of multiple myeloma

SIDE EFFECTS

Clinical Studies
Hypercalcemia of Malignancy
Transient mild elevation of temperature by at least 1 °C was noted 24 to 48 hours after administration of Aredia in 34% of patients in clinical trials. In the saline trial, 18% of patients had a temperature elevation of at least 1 °C 24 to 48 hours after treatment
Drug-related local soft-tissue symptoms (redness, swelling or induration and pain on palpation) at the site of catheterinsertion were most common in patients treated with 90 mg of Aredia. Symptomatic treatment resulted in rapid resolution in all patients

Rare cases of uveitis, iritis, scleritis, and episcleritis have been reported, including one case of scleritis, and one case of

General: Fluid overload, generalized pain

Cardiovascular: Hypertension

Gastrointestinal: Abdominal pain, anorexia, constipation, nausea, vomiting

Genitourinary: Urinary tract infection

Musculoskeletal: Bone pain

Laboratory Abnormality: Anemia, hypokalemia, hypomagnesemia, hypophosphatemia

Paget’s Disease

Transient mild elevation of temperature >1 °C above pretreatmentbaseline was noted within 48 hours after completion of treatment in 21% of the patients treated with 90 mg of Aredia in clinical trials

Drug-related musculoskeletalpain and nervoussystem symptoms (dizziness, headache, paresthesia, increased sweating) were more common in patients with Paget’s disease treated with 90 mg of Aredia than in patients with hypercalcemia of malignancy treated with the same dose

Adverse experiences considered to be related to trial drug, which occurred in at least 5% of patients with Paget’s disease treated with 90 mg of Aredia in two U.S. clinical trials, were fever, nausea, back pain, and bone pain

At least 10% of all Aredia-treated patients with Paget’s disease also experienced the following adverse experiences during clinical trials

Cardiovascular: Hypertension

Musculoskeletal: Arthrosis, bone pain

Nervous system: Headache

Most of these adverse experiences may have been related to the underlying disease state

Osteolytic Bone ----stases of Breast Cancer and Osteolytic Lesions of Multiple Myeloma
The most commonly reported (>15%) adverse experiences occurred with similar frequencies in the Aredia- and placebo-treatment groups

DRUG INTERACTIONS
Concomitant administration of a loopdiuretic had no effect on the calcium-lowering

action

 

of Aredia

Caution is indicated when Aredia is used with
other potentially nephrotoxic drugs