Adverse reactions : תופעות לוואי

4.8 Undesirable effects
The most common reported drug reaction is diarrhea which is usually mild and occurs more commonly with higher doses.

These adverse reactions may occur in connection with both oral and intravenous treatment, although the frequency of reactions may differ.
System Organ Class          Common                    Rare ≥ 1/100 ,< 1/10           ≥ 1/10,000 to < 1/1,000
Metabolism and                                        Symptomatic nutrition disorders         Asymptomatic              Hypocalcemia.
hypocalcemia              elevated serum parathyroid hormone levels associated with a reduction in serum calcium levels .
increased serum alkaline phosphatase levels.*
Gastrointestinal            Diarrhea** disorders                   Nausea**
Vomiting**
Hepatobiliary system        Increased                 Increased aminotransferases         aminotransferases usually within normal     ,exceeding twice the normal range                     range without associated
Hepatic failure
Skin and subcutaneous                                 Hypersensitivity-type skin tissue disorders                                      reaction 
*    in patients with metastatic disease, may also be due to hepatic and bone disease.
**   usually mild

Post-marketing experience
•     Eye disorders

Uveitis has been reported with Bonefos during post-marketing experience.
The following reactions have been reported with other bisphosphonates: conjunctivitis, episcleritis ans scleritis. Conjunctivitis was only reported with Bonefos in one patient concomitantly treated with another bisphosphonate.


•       Respiratory, thoratic and mediastinal disorders Impairment of respiratory function in patients with aspirin-sensitive asthma.
Hypersensitivity reactions manifesting as respiratory disorder.
•       Renal and urinary disorders Impairment of renal function (elevation of serum creatinine and proteinuria), severe renal damage especially after rapid intravenous infusion of high doses of clodronate (for dosage instructions see section "Posology and method of administration- Intravenous infusion- Patients with renal failure").
Single cases of renal failure have been reported, especially when clodronate has been used simultaneously with non-steroidal anti-inflammatory analgesics (NSAIDs), most often diclofenac.

.
•        Musculoskeletal and connective tissue disorders Isolated cases of osteonecrosis of the jaw have been reported, primarily in patients who were previously treated with amino-bisphsophonates such as zoledronate and pamidronate (see also section "Special warnings and special precautions for use"). Severe bone, joint, and/or muscle pain has been reported in patients taking Bonefos. However, such reports have been infrequent and in randomized placebo controlled studies no differences are apparent between placebo and Bonefos treated patients. The onset of symptoms varied from days to several months after starting Bonefos.

The following reactions have been reported during post-marketing experience (with rare incidence):
Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction) (see also section 4.4).


The most appropriate MedDRA term is used to describe a certain symptom and its synonyms and related conditions.