ADVERSE REACTIONS
Daily Oral Tablet
Treatment with BONIVA 2.5 mg daily oral tablet was studied in over 3900 patients in postmenopausal osteoporosis trials of up to 3 years duration. The overall adverse event profile of BONIVA 2.5 mg once daily tablet in these studies was similar to that of placebo.
Most adverse events were mild or moderate and did not lead to discontinuation. The incidence of serious adverse events was 20% in the placebo group and 23% in the BONIVA 2.5 mg daily oral tablet group. The percentage of patients who withdrew from treatment due to adverse events was approximately 17% in both the BONIVA 2.5 mg daily oral tablet group and the placebo group. Overall, and according to body system, there was no difference between BONIVA daily oral tablet and placebo, with adverse events of the digestive system being the most common reason for withdrawal.
Table 3 lists adverse events from the Treatment and Prevention Studies reported in ≥2% of patients and in more patients treated with BONIVA 2.5 mg daily oral tablet than patients treated with placebo. Adverse events are shown without attribution of causality.
Table 3 Adverse Events Occurring at a Frequency ≥2% and in More Patients Treated with BONIVA 2.5 mg Daily Oral Tablet than in Patients Treated with Placebo in the Osteoporosis Treatment and Prevention Studies | Body System | Placebo
%
(n=1134) | BONIVA 2.5 mg daily
%
(n=1140) |
|---|
| Body as a Whole | | |
| Back Pain | 12.2 | 13.5 |
| Pain in Extremity | 6.4 | 7.8 |
| Infection | 3.4 | 4.3 |
| Asthenia | 2.3 | 3.5 |
| Allergic Reaction | 1.9 | 2.5 |
| Digestive System | | |
| Dyspepsia | 9.8 | 11.9 |
| Diarrhea | 5.0 | 6.8 |
| Tooth Disorder | 2.3 | 3.5 |
| Vomiting | 2.1 | 2.7 |
| Gastritis | 1.9 | 2.2 |
| Metabolic and Nutritional Disorders | | |
| Hypercholesterolemia | 4.2 | 4.8 |
| Musculoskeletal System | | |
| Myalgia | 5.1 | 5.7 |
| Joint Disorder | 3.3 | 3.6 |
| Arthritis | 2.7 | 3.2 |
| Nervous System | | |
| Headache | 5.8 | 6.5 |
| Dizziness | 2.6 | 3.7 |
| Vertigo | 2.5 | 3.0 |
| Nerve Root Lesion | 1.9 | 2.2 |
| Respiratory System | | |
| Upper Respiratory Infection | 33.2 | 33.7 |
| Bronchitis | 6.8 | 10.0 |
| Pneumonia | 4.3 | 5.9 |
| Pharyngitis | 1.5 | 2.5 |
| Urogenital System | | |
| Urinary Tract Infection | 4.2 | 5.5 |
Quarterly IV Injection – DIVA Study
In a 1-year, double-blind, multicenter study comparing BONIVA Injection administered intravenously as 3 mg every 3 months to BONIVA 2.5 mg daily oral tablet in women with postmenopausal osteoporosis, the overall safety and tolerability profiles of the two dosing regimens were similar. The incidence of serious adverse events was 8.0% in the BONIVA 2.5 mg daily group and 7.5% in the BONIVA Injection 3 mg once every 3 months group. The percentage of patients who withdrew from treatment due to adverse events was approximately 6.7% in the BONIVA 2.5 mg daily group and 8.5% in the BONIVA Injection 3 mg every 3 months group.
Table 4 lists the adverse events reported in >2% of patients without attribution of causality.
Table 4 Adverse Events With an Incidence of at Least 2% in Patients Treated with BONIVA Injection (3 mg once every 3 months) or BONIVA Daily Oral Tablet (2.5 mg) | Body System/Adverse Event | BONIVA
2.5 mg Daily (Oral)
%
(n=465) | BONIVA
3 mg q 3 mo (IV)
%
(n=469) |
|---|
| Infections and Infestations | | |
| Influenza | 8.0 | 4.7 |
| Nasopharyngitis | 6.0 | 3.4 |
| Cystitis | 3.4 | 1.9 |
| Gastroenteritis | 3.4 | 1.5 |
| Urinary Tract Infection | 3.2 | 2.6 |
| Bronchitis | 2.8 | 2.1 |
| Upper Respiratory Tract Infection | 2.8 | 1.1 |
| Gastrointestinal Disorders | | |
| Abdominal PainIs a combination of abdominal pain and abdominal pain upper | 5.6 | 5.1 |
| Dyspepsia | 4.3 | 3.6 |
| Nausea | 4.3 | 2.1 |
| Constipation | 4.1 | 3.4 |
| Diarrhea | 2.4 | 2.8 |
| Gastritis | 2.2 | 1.9 |
| Musculoskeletal and Connective Tissue Disorders | | |
| Arthralgia | 8.6 | 9.6 |
| Back Pain | 7.5 | 7.0 |
| Localized Osteoarthritis | 2.4 | 1.5 |
| Pain in Extremity | 2.2 | 2.8 |
| Myalgia | 0.9 | 2.8 |
| Nervous System Disorders | | |
| Dizziness | 2.8 | 1.9 |
| Headache | 2.6 | 3.6 |
| Vascular Disorders | | |
| Hypertension | 7.1 | 5.3 |
| Psychiatric Disorders | | |
| Insomnia | 2.6 | 1.1 |
| Depression | 2.2 | 1.3 |
| General Disorders and Administration Site Conditions | | |
| Influenza-like IllnessCombination of influenza-like illness and acute phase reaction | 1.1 | 4.9 |
| Fatigue | 1.1 | 2.8 |
| Skin and Subcutaneous Tissue Disorders | | |
| RashCombination of rash, rash pruritic, rash macular, dermatitis, dermatitis allergic, exanthem, erythema, rash papular, rash generalized, dermatitis medicamentosa, rash erythematous | 2.8 | 2.3 |
| Metabolism and Nutrition Disorders | | |
| Hypercholesterolemia | 4.3 | 1.5 |
Acute Phase Reaction-like Events
Symptoms consistent with acute phase reaction (APR) have been reported with intravenous bisphosphonate use. The overall incidence of patients with APR-like events was higher in the intravenous treatment group (4% in the BONIVA 2.5 mg daily oral tablet group vs. 10% in the BONIVA Injection 3 mg once every 3 months group). These incidence rates are based on reporting of any of 33 potential APR-like symptoms within 3 days of an IV dose and for a duration of 7 days or less. In most cases, no specific treatment was required and the symptoms subsided within 24 to 48 hours.
Injection Site Reactions
Local reactions at the injection site, such as redness or swelling, were observed infrequently, but at a higher incidence in patients treated with BONIVA Injection 3 mg every 3 months (<2%; 8/469) than in patients treated with placebo injections (<1%; 1/465). In most cases, the reaction was of mild to moderate severity.
Ocular Adverse Events
Bisphosphonates may be associated with ocular inflammation such as uveitis and scleritis. In some cases, these events did not resolve until the bisphosphonate was discontinued.
Laboratory Test Findings
There were no clinically significant changes from baseline values or shifts in any laboratory variable with oral ibandronate. As expected with bisphosphonate treatment, a decrease in total alkaline phosphatase levels was seen with 2.5 mg daily oral ibandronate compared to placebo. There was no difference compared with placebo for laboratory abnormalities indicative of hepatic or renal dysfunction, hypocalcemia, or hypophosphatemia. There also was no evidence that BONIVA Injection 3 mg every 3 months induced clinically significant laboratory abnormalities indicative of hepatic or renal dysfunction compared to BONIVA 2.5 mg daily oral tablet.
|
