IBANDRONATE SODIUM (Page 3 of 8)

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 ibandronate sodium 2.5 mg (ibandronate) daily oral tablet group vs. 10% in the ibandronate sodium injection 3 mg (ibandronate) once every 3 months group). These incidence rates are based upon reporting of any of 33 potential APR-like symptoms within 3 days of an intravenous dose and lasting 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 at a higher incidence in patients treated with ibandronate sodium injection 3 mg (ibandronate) every 3 months (1.7%; 8/469) than in patients treated with placebo injections (0.2%; 1/465). In most cases, the reaction was of mild to moderate severity.

Daily Oral Tablet –

The safety of ibandronate sodium 2.5 mg (ibandronate) once daily in the treatment and prevention of postmenopausal osteoporosis was assessed in 3577 patients aged 41 — 82 years. The duration of the trials was 2 to 3 years, with 1134 patients exposed to placebo and 1140 exposed to ibandronate sodium 2.5 mg (ibandronate). Patients with pre-existing gastrointestinal disease and concomitant use of non-steroidal anti-inflammatory drugs, proton pump inhibitors and H2 antagonists were included in these clinical trials. All patients received 500 mg calcium plus 400 international units vitamin D supplementation daily.

The incidence of all-cause mortality was 1% in the placebo group and 1.2% in the ibandronate sodium 2.5 mg (ibandronate) daily group. The incidence of serious adverse reactions was 20% in the placebo group and 23% in the ibandronate sodium 2.5 mg (ibandronate) daily oral tablet group. The percentage of patients who withdrew from treatment due to adverse reactions was approximately 17% in both the placebo group and the ibandronate sodium 2.5 mg (ibandronate) daily oral tablet group. Table 2 lists adverse reactions from the Treatment and Prevention Studies reported in greater than or equal to 2% of patients and in more patients treated with ibandronate sodium 2.5 mg (ibandronate) daily oral tablet than patients treated with placebo.

Table 2 Adverse Reactions Occurring at an Incidence greater than or equal to 2% and in More Patients Treated with Ibandronate Sodium 2.5 mg (ibandronate) Daily Oral Tablet than in Patients Treated with Placebo in the Osteoporosis Treatment and Prevention Studies

Body System	Placebo % (n=1134)	Ibandronate Sodium 2.5 mg (ibandronate) daily % (n=1140)
Body as a Whole
Back Pain	12	14
Pain in Extremity	6	8
Asthenia	2	4
Allergic Reaction	2	3
Digestive System
Dyspepsia	10	12
Diarrhea	5	7
Tooth Disorder	2	4
Vomiting	2	3
Gastritis	2	2
Musculoskeletal System
Myalgia	5	6
Joint Disorder	3	4
Arthritis	3	3
Nervous System
Headache	6	7
Dizziness	3	4
Vertigo	3	3
Respiratory System
Upper Respiratory Infection	33	34
Bronchitis	7	10
Pneumonia	4	6
Pharyngitis	2	3
Urogenital System
Urinary Tract Infection	4	6

Gastrointestinal Adverse Reactions

The incidence of selected gastrointestinal adverse reactions in the placebo and ibandronate sodium 2.5 mg (ibandronate) daily groups were: dyspepsia (10% vs. 12%), diarrhea (5% vs. 7%), and abdominal pain (5% vs. 6%).

Musculoskeletal Adverse Reactions

The incidence of selected musculoskeletal adverse reactions in the placebo and ibandronate sodium 2.5 mg (ibandronate) daily groups were: back pain (12% vs. 14%), arthralgia (14% vs. 14%) and myalgia (5% vs. 6%).

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ibandronate sodium injection. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hypersensitivity : Allergic reactions including anaphylaxis with fatalities, angioedema, asthma exacerbation, bronchospasm, rash, Stevens-Johnson syndrome, erythema multiforme, and dermatitis bullous [see Contraindications (4) , Warnings and Precautions (5.2) ] .

Hypocalcemia : Hypocalcemia [see Warnings and Precautions (5.1) ].

Renal Toxicity : Acute renal failure [see Warnings and Precautions (5.3) ].

Osteonecrosis of the Jaw : Osteonecrosis of the jaw and other oro-facial sites, including the external auditory canal [see Warnings and Precautions (5.5) ] .

Musculoskeletal Pain : Bone, joint, or muscle pain (musculoskeletal pain), described as severe or incapacitating [see Warnings and Precautions (5.6) ] .

Atypical Femoral Shaft Fracture : Atypical, low-energy, or low-trauma fractures of the femoral shaft [see Warnings and Precautions (5.7) ].

Eye Inflammation : Iritis and uveitis. In some cases with other bisphosphonates, these events did not resolve until the bisphosphonate was discontinued.