|Manufacturer:||Novartis Pharmaceuticals Corporation|
Reclast was studied in male and female patients with moderate to severe Paget’s disease of bone, defined as serum alkaline phosphatase level at least twice the upper limit of the age-specific normal reference range at the time of study entry.
Diagnosis was confirmed by radiographic evidence. The efficacy of one infusion of 5 mg Reclast vs.
oral daily doses of 30 mg risedronate for 2 months was demonstrated in two identically designed 6-month randomized, double blind trials.
The mean age of patients in the two trials was 70.
Ninety-three percent (93%) of patients were Caucasian.
Therapeutic response was defined as either normalization of serum alkaline phosphatase (SAP) or a reduction of at least 75% from baseline in total SAP excess at the end of 6 months.
SAP excess was defined as the difference between the measured level and midpoint of normal range.
In both trials Reclast demonstrated a superior and more rapid therapeutic response compared with risedronate and returned more patients to normal levels of bone turnover, as evidenced by biochemical markers of formation (SAP, serum N-terminal propeptide of type I collagen [P1NP]) and resorption (serum CTx 1 [cross-linked C-telopeptides of type I collagen] and urine ?-CTx).
The 6-month combined data from both trials showed that 96% (169/176) of Reclast-treated patients achieved a therapeutic response as compared with 74% (127/171) of patients treated with risedronate.
Most Reclast patients achieved a therapeutic response by the Day 63 visit.
In addition, at 6 months, 89% (156/176) of Reclast-treated patients achieved normalization of SAP levels, compared to 58% (99/171) of patients treated with risedronate (p<0.0001) (see Figure 2).
Therapeutic Response/Serum Alkaline Phosphatase (SAP) Normalization Over Time The therapeutic response to Reclast was similar across demographic and disease-severity groups defined by gender, age, previous bisphosphonate use, and disease severity.
At 6 months, the percentage of Reclast-treated patients who achieved therapeutic response was 97% and 95%, respectively, in each of the baseline disease severity subgroups (baseline SAP < 3xULN, > 3xULN) compared to 75% and 74%, respectively, for the same disease severity subgroups of risedronate-treated patients.
In patients who had previously received treatment with oral bisphosphonates, therapeutic response rates were 96% and 55% for Reclast and risedronate, respectively.
The comparatively low risedronate response was due to the low response rate (7/23, 30%) in patients previously treated with risedronate.
In patients naïve to previous treatment, a greater therapeutic response was also observed with Reclast (98%) relative to risedronate (86%).
In patients with symptomatic pain at screening, therapeutic response rates were 94% and 70% for Reclast and risedronate respectively.
For patients without pain at screening, therapeutic response rates were 100% and 82% for Reclast and risedronate respectively.
Bone histology was evaluated in 7 patients with Paget’s disease 6 months after being treated with Reclast 5 mg.Bone biopsy results showed bone of normal quality with no evidence of impaired bone remodeling and no evidence of mineralization defect.
Hypocalcemia (4.1)Hypersensitivity to any component of Reclast (4.2, 6.2) -----------WARNINGS AND PRECAUTIONS------------Reclast contains the same active ingredient found in Zometa.
Patients receiving Zometa should not receive Reclast (5.1)Patients must be adequately supplemented with calcium and vitamin D (5.2)A single dose should not exceed 5 mg and the duration of infusion should be no less than 15 minutes (2.1, 2.2, 5.3)Renal toxicity may be greater in patients with renal impairment.
Treatment in patients with severe renal impairment (creatinine clearance <35 mL/min) is not recommended.
Monitor serum creatinine before each dose (5.3)Osteonecrosis of the jaw has been reported rarely in postmenopausal osteoporosis patients treated with bisphosphonates, including zoledronic acid.
All patients should have a routine oral exam by the prescriber prior to treatment (5.4)Reclast can cause fetal harm.
Women of childbearing potential should be advised of the potential hazard to the fetus and to avoid becoming pregnant (5.5, 8.1)Severe incapacitating bone, joint, and/or muscle pain may occur.Withhold future doses of Reclast if severe symptoms occur (5.6)