Five of 231 patients (2%) who received pamidronate disodium during the four U.S. controlled hypercalcemia clinical studies were reported to have had seizures, 2 of whom had preexisting seizure disorders. None of the seizures were considered to be drug-related by the investigators. However, a possible relationship between the drug and the occurrence of seizures cannot be ruled out. It should be noted that in the saline arm 1 patient (4%) had a seizure.

There are no controlled clinical trials comparing the efficacy and safety of 90 mg pamidronate disodium over 24 hours to 2 hours in patients with hypercalcemia of malignancy. However, a comparison of data from separate clinical trials suggests that the overall safety profile in patients who received 90 mg pamidronate disodium over 24 hours is similar to those who received 90 mg pamidronate disodium over 2 hours. The only notable differences observed were an increase in the proportion of patients in the pamidronate disodium 24 hour group who experienced fluid overload and electrolyte/mineral abnormalities.

At least 15% of patients treated with pamidronate disodium for hypercalcemia of malignancy also experienced the following adverse events during a clinical trial:

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

The following table lists the adverse experiences considered to be treatment-related during comparative, controlled U.S. trials.

Treatment-Related Adverse Experiences Reported in Three U.S. Controlled Clinical Trials   Percent of Patients
 
Pamidronate Disodium
 Etidronate disodium
 Saline
 
60 mg over 4 hr
 60 mg
over 24 hr
 90 mg
over 24 hr
 7.5 mg/kg
x 3 days
 
 n=23
 n=73
 n=17
 n=35
 n=23
 
General
 
Edema
 0
 1
 0
 0
 0
 
Fatigue
 0
 0
 12
 0
 0
 
Fever
 26
 19
 18
 9
 0
 
Fluid overload
 0
 0
 0
 6
 0
 
Infusion-site reaction
 0
 4
 18
 0
 0
 
Moniliasis
 0
 0
 6
 0
 0
 
Rigors
 0
 0
 0
 0
 4
 
Gastrointestinal
 
Abdominal pain
 0
 1
 0
 0
 0
 
Anorexia
 4
 1
 12
 0
 0
 
Constipation
 4
 0
 6
 3
 0
 
Diarrhea
 0
 1
 0
 0
 0
 
Dyspepsia
 4
 0
 0
 0
 0
 
Gastrointestinal hemorrhage
 0