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Alendronate (Alendronate Sodium) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

Clinical Studies


In clinical studies of up to five years in duration adverse experiences associated with alendronate sodium usually were mild, and generally did not require discontinuation of therapy.
 
Alendronate sodium has been evaluated for safety in approximately 8000 postmenopausal women in clinical studies.

Treatment of osteoporosis

Postmenopausal women


In two identically designed, three-year, placebo-controlled, double-blind, multicenter studies (United States and Multinational; n=994), discontinuation of therapy due to any clinical adverse experience occurred in 4.1% of 196 patients treated with alendronate sodium 10 mg/day and 6% of 397 patients treated with placebo. In the Fracture Intervention Trial (n=6459), discontinuation of therapy due to any clinical adverse experience occurred in 9.1% of 3236 patients treated with alendronate sodium 5 mg/day for 2 years and 10 mg/day for either one or two additional years and 10.1% of 3223 patients treated with placebo. Discontinuations due to upper gastrointestinal adverse experiences were: alendronate sodium, 3.2%; placebo, 2.7%. In these study populations, 49 to 54% had a history of gastrointestinal disorders at baseline and 54 to 89% used nonsteroidal anti-inflammatory drugs or aspirin at some time during the studies. Adverse experiences from these studies considered by the investigators as possibly, probably, or definitely drug related in ≥1% of patients treated with either alendronate sodium or placebo are presented in the following table.
Osteoporosis Treatment Studies in Postmenopausal Women Adverse Experiences Considered Possibly, Probably, or Definitely Drug Related by the Investigators and Reported in ≥1% of Patients
United States/Multinational Studies     Fracture Intervention Trial

 
Alendronate Sodium*
%
(n=196)
Placebo
%
(n=397)
 Alendronate Sodium**
 %
 (n=3236)
 Placebo
%
(n=3223)
*10 mg/day for three years
**5 mg/day for 2 years and 10 mg/day for either 1 or 2 additional years

Gastrointestinal

    abdominal pain

    nausea

    dyspepsia

    constipation

    diarrhea

    flatulence

    acid regurgitation

    esophageal ulcer

    vomiting

    dysphagia

    abdominal distention

    gastritis

Musculoskeletal

    musculoskeletal (bone,
       muscle or joint) pain

    muscle cramp

Nervous System/Psychiatric

    headache

    dizziness

Special Senses

    taste perversion

          
        
                 6.6
                  
                 3.6
                  
                 3.6
                  
                 3.1
                  
                 3.1
                  
                 2.6
                  
                 2
                  
                 1.5
                  
                 1
                  
                 1
                 
                 1
                   
                 0.5
                  


                 4.1
                 
 
                 0
                  


                 2.6
                   
                 0
                  
             
 
               0.5

  
 
    4.8
    
    4
    
    3.5
    
    1.8
    
    1.8
    
    0.5
    
    4.3
    
    0
    
    1.5
    
    0
    
    0.8
   
    1.3
    


    2.5
    

    1
   


    1.5
    
    1
   


    1


          
                 1.5
                  
                 1.1
                  
                 1.1
                  
                 0
                  
                 0.6
                  
                 0.2
                  
                 1.1
                  
                 0.1
                  
                 0.2
                  
                 0.1
                 
                 0
                   
                 0.6
                  


                 0.4
       
           
                 0.2
                  


                 0.2
                  
                 0
                  


                 0.1

  
 
     1.5
    
    1.5
    
    1.2
    
    0.2
    
    0.3
    
    0.3
    
    0.9
    
    0.1
    
    0.3
    
    0.1
    
    0
   
    0.7
    


    0.3
    

    0.1
   
 

    0.2
    
    0.1
   
 

    0
 

Rarely, rash and erythema have occurred.
 
One patient treated with alendronate sodium (10 mg/day), who had a history of peptic ulcer disease and gastrectomy and who was taking concomitant aspirin developed an anastomotic ulcer with mild hemorrhage, which was considered drug related. Aspirin and alendronate sodium were discontinued and the patient recovered.
 
The adverse experience profile was similar for the 401 patients treated with either 5 or 20 mg doses of alendronate sodium in the United States and Multinational studies. The adverse experience profile for the 296 patients who received continued treatment with either 5 or 10 mg doses of alendronate sodium in the two-year extension of these studies (treatment years 4 and 5) was similar to that observed during the three-year placebo-controlled period. During the extension period, of the 151 patients treated with alendronate sodium 10 mg/day, the proportion of patients who discontinued therapy due to any clinical adverse experience was similar to that during the first three years of the study.
 
In a one-year, double-blind, multicenter study, the overall safety and tolerability profiles of once weekly alendronate sodium 70 mg and alendronate sodium 10 mg daily were similar. The adverse experiences considered by the investigators as possibly, probably, or definitely drug related in ≥1% of patients in either treatment group are presented in the following table.
Osteoporosis Treatment Studies in Postmenopausal Women Adverse Experiences Considered Possibly, Probably, or Definitely Drug Related by the Investigators and Reported in ≥1% of Patients
Once Weekly
Alendronate Sodium
70 mg
%
(n=519)
Alendronate Sodium
10 mg/day
 %
(n=370)

Gastrointestinal

    abdominal pain

    dyspepsia

    acid regurgitation

    nausea  

    abdominal distention

    constipation

    flatulence

    gastritis

    gastric ulcer

            

              3.7
            
              2.7
           
              1.9
            
              1.9
             
              1
           
              0.8
            
              0.4
           
              0.2
             
              0

           
    
              3
             
              2.2
             
              2.4
             
              2.4
             
              1.4
             
              1.6
             
              1.6
             
              1.1
             
              1.1

Musculoskeletal

    musculoskeletal (bone, muscle,
         joint) pain

    muscle cramp

           
 
              2.9
            

              0.2

          

              3.2
             
          
              1.1

Men


In two placebo-controlled, double-blind, multicenter studies in men (a two-year study of alendronate sodium 10 mg/day and a one-year study of once weekly alendronate sodium 70 mg) the rates of discontinuation of therapy due to any clinical adverse experience were 2.7% for alendronate sodium 10 mg/day vs. 10.5% for placebo, and 6.4% for once weekly alendronate sodium 70 mg vs. 8.6% for placebo. The adverse experiences considered by the investigators as possibly, probably, or definitely drug related in ≥2% of patients treated with either alendronate sodium or placebo are presented in the following table.
Osteoporosis Studies in Men Adverse Experiences Considered Possibly, Probably, or Definitely Drug Related by the Investigators and Reported in ≥2% of Patients
           Two-year Study             One-year Study

 
Alendronate Sodium
10 mg/day
%
(n=146)
Placebo
%
 (n=95)
Once Weekly
Alendronate Sodium
70 mg
%
(n=109)
Placebo
%
(n=58)

Gastrointestinal

    acid regurgitation

    flatulence
 
    gastroesophageal
      reflux disease
 
    dyspepsia
 
    diarrhea
 
    abdominal pain 
 
    nausea

 

              4.1

              4.1

              0.7

 
              3.4

              1.4

              2.1

              2.1

 

    3.2

    1.1

    3.2

 
     0

    1.1

    1.1

    0

 

               0

               0

              2.8

 
              2.8

              2.8

              0.9

               0

 

      0

      0

      0

 
     1.7

      0

     3.4

      0

Prevention of osteoporosis in postmenopausal women


The safety of alendronate sodium 5 mg/day in postmenopausal women 40 to 60 years of age has been evaluated in three double-blind, placebo-controlled studies involving over 1,400 patients randomized to receive alendronate sodium for either two or three years. In these studies the overall safety profiles of alendronate sodium 5 mg/day and placebo were similar. Discontinuation of therapy due to any clinical adverse experience occurred in 7.5% of 642 patients treated with alendronate sodium 5 mg/day and 5.7% of 648 patients treated with placebo.
 
In a one-year, double-blind, multicenter study, the overall safety and tolerability profiles of once weekly alendronate sodium 35 mg and alendronate sodium 5 mg daily were similar.
 
The adverse experiences from these studies considered by the investigators as possibly, probably, or definitely drug related in ≥1% of patients treated with either once weekly alendronate sodium 35 mg, alendronate sodium 5 mg/day or placebo are presented in the following table.
Osteoporosis Prevention Studies in Postmenopausal Women Adverse Experiences Considered Possibly, Probably, or Definitely Drug Related by the Investigators and Reported in ≥1% of Patients

 
       Two/Three-Year Studies
                        One-Year Study
Alendronate Sodium
        5 mg/day
              %
          (n=642)
Placebo
    %
  (n=648)
Alendronate Sodium
       5 mg/day
            %
        (n=361)
      Once Weekly
Alendronate Sodium
           35 mg
              %
          (n=362)

Gastrointestinal

    dyspepsia

    abdominal pain

    acid regurgitation

    nausea

    diarrhea

    constipation

    abdominal distention

Musculoskeletal

    musculoskeletal (bone,
        muscle or joint)
        pain

 

            1.9

            1.7

            1.4

            1.4

            1.1

            0.9

            0.2

 

            0.8

 

    1.4

    3.4

    2.5

    1.4

    1.7

    0.5

    0.3

 

    0.9

 

            2.2

            4.2

            4.2

            2.5

            1.1

            1.7

            1.4

 

            1.9

        

            1.7
            
            2.2

            4.7

            1.4

            0.6

            0.3

            1.1
 

            
            2.2

Concomitant use with estrogen/hormone replacement therapy


In two studies (of one and two years' duration) of postmenopausal osteoporotic women (total: n=853), the safety and tolerability profile of combined treatment with alendronate sodium 10 mg once daily and estrogen ± progestin (n=354) was consistent with those of the individual treatments.

Treatment of glucocorticoid-induced osteoporosis


In two, one-year, placebo-controlled, double-blind, multicenter studies in patients receiving glucocorticoid treatment, the overall safety and tolerability profiles of alendronate sodium 5 and 10 mg/day were generally similar to that of placebo. The adverse experiences considered by the investigators as possibly, probably, or definitely drug related in ≥1% of patients treated with either alendronate sodium 5 or 10 mg/day or placebo are presented in the following table.
One-Year Studies in Glucocorticoid-Treated Patients Adverse Experiences Considered Possibly, Probably, or Definitely Drug Related by the Investigators and Reported in ≥1% of Patients

 
Alendronate Sodium
        10 mg/day
              %
          (n=157)
Alendronate Sodium
        5 mg/day
              %
          (n=161)
Placebo
    %
  (n=159)

Gastrointestinal

    abdominal pain

    acid regurgitation

    constipation

    melena

    nausea

    diarrhea

Nervous System/Psychiatric

    headache

 

            3.2

            2.5

            1.3

            1.3

            0.6

            0

 

            0.6

 

            1.9

            1.9

            0.6

            0

            1.2

            0

 

            0

 

    0

    1.3

    0

    0   

    0.6

    1.3

 

    1.3

The overall safety and tolerability profile in the glucocorticoid-induced osteoporosis population that continued therapy for the second year of the studies (alendronate sodium: n=147) was consistent with that observed in the first year.

Paget's disease of bone


In clinical studies (osteoporosis and Paget's disease), adverse experiences reported in 175 patients taking alendronate sodium 40 mg/day for 3 to 12 months were similar to those in postmenopausal women treated with alendronate sodium 10 mg/day. However, there was an apparent increased incidence of upper gastrointestinal adverse experiences in patients taking alendronate sodium 40 mg/day (17.7% alendronate sodium vs. 10.2% placebo). One case of esophagitis and two cases of gastritis resulted in discontinuation of treatment.
 
Additionally, musculoskeletal (bone, muscle or joint) pain, which has been described in patients with Paget's disease treated with other bisphosphonates, was considered by the investigators as possibly, probably, or definitely drug related in approximately 6% of patients treated with alendronate sodium 40 mg/day versus approximately 1% of patients treated with placebo, but rarely resulted in discontinuation of therapy. Discontinuation of therapy due to any clinical adverse experience occurred in 6.4% of patients with Paget's disease treated with alendronate sodium 40 mg/day and 2.4% of patients treated with placebo.

Osteogenesis Imperfecta


Alendronate sodium tablets are not indicated for use in children.
 
The overall safety profile of alendronate sodium in OI patients treated for up to 24 months was generally similar to that of adults with osteoporosis treated with alendronate sodium. However, there was an increased occurrence of vomiting in OI patients treated with alendronate sodium compared to placebo. During the 24-month treatment period, vomiting was observed in 32 of 109 (29.4%) patients treated with alendronate sodium and 3 of 30 (10%) patients treated with placebo.
 
In a pharmacokinetic study, 6 of 24 pediatric OI patients who received a single oral dose of alendronate sodium 35 or 70 mg developed fever, flu-like symptoms, and/or mild lymphocytopenia within 24 to 48 hours after administration. These events, lasting no more than 2 to 3 days and responding to acetaminophen, are consistent with an acute-phase response that has been reported in patients receiving bisphosphonates, including alendronate sodium. See ADVERSE REACTIONS, Post-Marketing Experience, Body as a Whole.

Laboratory Test Findings


In double-blind, multicenter, controlled studies, asymptomatic, mild, and transient decreases in serum calcium and phosphate were observed in approximately 18% and 10%, respectively, of patients taking alendronate sodium versus approximately 12% and 3% of those taking placebo. However, the incidences of decreases in serum calcium to <8 mg/dL (2 mM) and serum phosphate to ≤2 mg/dL (0.65 mM) were similar in both treatment groups.

Post-Marketing Experience


The following adverse reactions have been reported in post-marketing use:

Body as a Whole:
hypersensitivity reactions including urticaria and rarely angioedema. Transient symptoms of myalgia, malaise, asthenia and rarely, fever have been reported with alendronate sodium, typically in association with initiation of treatment. Rarely, symptomatic hypocalcemia has occurred, generally in association with predisposing conditions. Rarely, peripheral edema.

Gastrointestinal:
esophagitis, esophageal erosions, esophageal ulcers, rarely esophageal stricture or perforation, and oropharyngeal ulceration. Gastric or duodenal ulcers, some severe and with complications have also been reported (see WARNINGS, PRECAUTIONS, Information for Patients, and DOSAGE AND ADMINISTRATION).
 
Localized osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection, often with delayed healing, has been reported rarely (see PRECAUTIONS, Dental).

Musculoskeletal:
bone, joint, and/or muscle pain, occasionally severe, and rarely incapacitating (see PRECAUTIONS, Musculoskeletal Pain); joint swelling.

Nervous system:
dizziness and vertigo.

Skin:
rash (occasionally with photosensitivity), pruritus, alopecia, rarely severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

Special Senses: 
rarely uveitis, scleritis or episcleritis.



REPORTS OF SUSPECTED ALENDRONATE SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Alendronate. The information is not vetted and should not be considered as verified clinical evidence.

Possible Alendronate side effects / adverse reactions in 57 year old female

Reported by a physician from United States on 2012-06-06

Patient: 57 year old female

Reactions: Diarrhoea, Diverticulitis, Anastomotic Leak

Adverse event resulted in: hospitalization

Suspect drug(s):
Blinded Vaccine
    Start date: 2010-10-05
    End date: 2010-10-05

Alendronate
    Dosage: 70mg per day
    Administration route: Oral
    Indication: Osteopenia
    Start date: 2010-02-01

Calcium
    Dosage: 600mg per day
    Administration route: Oral
    Indication: Osteopenia
    Start date: 2005-01-01

Wellbutrin SR
    Dosage: 150mg per day
    Administration route: Oral
    Indication: Depression
    Start date: 2009-01-01

Vytorin
    Administration route: Oral
    Indication: Dyslipidaemia
    Start date: 2000-01-01



See index of all Alendronate side effect reports >>

Drug label data at the top of this Page last updated: 2009-08-20

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