Adverse reactions : תופעות לוואי

4.8   Undesirable effects

In a one-year study in post-menopausal women with osteoporosis the overall safety profiles of alendronate 70 mg once weekly (n=519) and alendronate 10 mg/day (n=370) were similar.

In two three-year studies of virtually identical design, in post-menopausal women (alendronate 10 mg: n=196, placebo: n=397) the overall safety profiles of alendronate 10 mg/day and placebo were similar.

Adverse reactions reported by the investigators as possibly, probably or definitely drug-related are presented below if they occurred in ≥ 1% in either treatment group in the one-year study, or in ≥ 1% of patients treated with alendronate 10 mg/day and at a greater incidence than in patients given placebo in the three-year studies:


ONE-YEAR STUDY                         THREE-YEAR STUDIES alendronate    alendronate             alendronate
Once Weekly
70 mg                                                      placebo
10 mg/day               10mg/day
(n=397)
(n=519)             (n=370)            (n=196)
%
%                   %                  %
Gastro-intestinal abdominal pain            3.7                 3.0                6.6                 4.8 dyspepsia                 2.7                 2.2                3.6                 3.5 acid regurgitation        1.9                 2.4                2.0                 4.3 nausea                    1.9                 2.4                3.6                 4.0 abdominal distension      1.0                 1.4                1.0                 0.8 constipation              0.8                 1.6                3.1                 1.8 diarrhoea                 0.6                 0.5                3.1                 1.8 dysphagia                 0.4                 0.5                1.0                 0.0 flatulence                0.4                 1.6                2.6                 0.5 gastritis                 0.2                 1.1                0.5                 1.3 gastric ulcer             0.0                 1.1                0.0                 0.0 oesophageal ulcer         0.0                 0.0                1.5                 0.0 Musculoskeletal musculoskeletal pain      2.9                 3.2                4.1                 2.5 (bone, muscle or joint) muscle cramp              0.2                 1.1                0.0                 1.0 Neurological headache                  0.4                 0.3                2.6                 1.5 
In a one-year post-authorization safety study the investigators reported related to Binosto, an oral buffered alendronate solution, the following adverse events occurring in ≥ 0.5 % of the patients: 
ONE-YEAR, single arm, observational study in post- menopausal women with osteoporosis alendronate, oral buffered solution
Once weekly 70 mg
(n=1028)
%
Gastro-intestinal abdominal pain                          2.0 dyspepsia                               2.7 gastroesophageal                        2.4 reflux disease nausea                                  2.2 abdominal distension                    0.6 gastritis                               0.9
Musculoskeletal musculoskeletal pain                    1.2
(bone, muscle or joint)


The following adverse reactions have been reported during clinical studies and/or post-marketing use of oral alendronate tablets:


Adverse reactions
Very             Common               Uncommon               Rare              Very Rare Common             (≥ 1/100,            (>1/1,000,          (>1/10,000,         (<1/10,000) (≥ 1/10)            < 1/10)              <1/100)             <1/1,000) 
Immune                                                                      hypersensitivity system                                                                      reactions disorders                                                                   including urticaria and angioedema
Metabolism                                                                  symptomatic and nutrition                                                               hypocalcaemia, disorders                                                                   often in association with predisposing conditions#.
Nervous                           headache,          dysgeusia§ system                            dizziness§ disorders
Eye disorders                                        eye inflammation (uveitis, scleritis,
or episcleritis)
Ear and                           vertigo§ labyrinth disorders
‡Gastro-                          abdominal          nausea, vomiting,      oesophageal intestinal                        pain,              gastritis,             stricture*, disorders‡                        dyspepsia,         oesophagitis*,         oropharyngeal constipation,      oesophageal            ulceration*,
diarrhoea,         erosions*,             upper flatulence,        melena§                gastrointestinal oesophageal                               PUBs ulcer*,                                   (perforation,
dysphagia*,                               ulcers,
abdominal                                 bleeding)# distension, acid regurgitation
Skin and                          alopecia§,         rash, erythema         rash with subcuta-                          pruritus§                                 photosensitivity, neous tissue                                                                severe skin disorders                                                                   reactions including
Stevens-Johnson syndrome and toxic epidermal necrolysis+
Musculo-        musculo-          joint swelling§                           Osteonecrosis of    Osteonecrosis of skeletal,       skeletal                                                    the jaw#+,          the external connective      (bone, muscle                                               atypical            auditory canal tissue and      or joint) pain,                                             subtrochanteric     (bisphosphonate bone            which is                                                    and diaphyseal      class adverse disorders        sometimes                                                femoral             reaction) severe#§                                                 fractures
(bisphosphonate class adverse reaction) #

General                           asthenia§,         transient disorders and                     peripheral         symptoms as in administra-                       oedema§            an acute-phase tion site                                            response condition                                            (myalgia, malaise and rarely, fever) typically in association with initiation of treatment§.

#
See section 4.4
§
Frequency in Clinical Trials was similar in the drug and placebo group.
*See sections 4.2 and 4.4
+
This adverse reaction was identified through post-marketing surveillance. The frequency of rare was estimated based on relevant clinical trials.
‡These adverse reactions were identified with the tablet form, and may not all apply to (Binosto) 70 mg, which is taken as a buffered oral solution.

Reporting suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il/