atient to discontinue participation in the trial. One was due to interstitial pneumonitis, another to malaise and dyspnea. One pamidronate disodium patient discontinued the trial due to a symptomatic hypocalcemia. Another pamidronate disodium patient discontinued therapy due to severe bone pain after each infusion, which the investigator felt was trial-drug-related.
Renal Toxicity
In a study of the safety and efficacy of pamidronate disodium 90 mg (2 hour infusion) versus Zometa 4 mg (15 minute infusion) in bone metastases patients with multiple myeloma or breast cancer, renal deterioration was defined as an increase in serum creatinine of 0.5 mg/dL for patients with normal baseline creatinine (<1.4 mg/dL) or an increase of 1.0 mg/dL for patients with an abnormal baseline creatinine (≥1.4 mg/dL). The following are data on the incidence of renal deterioration in patients in this trial. See Table below.
Incidence of Renal Function Deterioration in Multiple Myeloma and Breast Cancer Patients with Normal and Abnormal Serum Creatinine at Baseline* *
Patients were randomized following the 15-minute infusion amendment for the Zometa arm.
Patient Population/Baseline Creatinine
Pamidronate Disodium 90 mg/2 hours
Zometa® 4 mg/15 minutes
n/N
(%)
n/N
(%)
Normal
20/246
(8.1%)
23/246
(9.3%)
Abnormal
2/22
(9.1%)
1/26
(3.8%)
Total
22/268
(8.2%)
24/272
(8.8%)
Post-Marketing Experience
The following adverse reactions have been reported in post-marketing use: General: reactivation of Herpes simplex and Herpes zoster, influenza-like symptoms;CNS: confusion and visual hallucinations, sometimes in the presence of electrolyte imbalance; Skin: rash, pruritus; Special senses: conjunctivitis; Renal: focal segmental glomerulosclerosis including the collapsing variant, nephrotic syndrome; Laboratory abnormalities: hyperkalemia, hypernatremia, hematuria. Rare instances of allergic manifestations have been reported, including hypotension, dyspnea, or angioedema, and very rarely, anaphylactic shock. Pamidronate disodium is contraindicated in patients with clinically significant hypersensitivity to pamidronate disodium or other bisphosphonates (see CONTRAINDICATIONS).
Cases of osteonecrosis (primarily involving the jaw) have been reported predominantly in cancer patients treated with intravenous bisphosphonates, including pamidronate disodium. Many of these patients were also receiving chemotherapy and corticosteroids which may be risk factors for ONJ. Data suggest a greater frequency of reports of ONJ in certain cancers, such as advanced breast cancer and multiple myeloma. The majority of the reported cases are in cancer patients following invasive dental procedures, such as tooth extraction. It is therefore prudent to avoid invasive dental procedures as recovery may be prolonged. (See PRECAUTIONS.)
OVERDOSAGE
There have been several cases of drug maladministration of intravenous pamidronate disodium in hypercalcemia patients with total doses of 225 mg to 300 mg given over 2 1/2 to 4 days. All of these patients survived, but they experienced hypocalcemia that required intravenous and/or oral administration of calcium. Single do
