Alendronate

Name: Alendronate

What is alendronate, and how does it work (mechanism of action)?

Alendronate is in a class of medications called bisphosphonates. The bisphosphonate class includes etidronate (Didronel), ibandronate (Boniva), pamidronate (Aredia), risedronate (Actonel), and tiludronate (Skelid). Bisphosphonates are used for treating osteoporosis (reduced density of bone that leads to fractures) and bone pain from diseases such as metastatic breast cancer, multiple myeloma, and Paget's disease. Bone is in a constant state of remodeling. New bone is laid down by cells called osteoblasts while old bone is removed by cells called osteoclasts. Bisphosphonates strengthen bone by inhibiting bone removal (resorption) by osteoclasts. After menopause, there is an increased rate of bone loss leading to osteoporosis, and alendronate has been shown to increase bone density and decrease fractures of bones. The FDA approved alendronate in September 1995.

What are the uses for alendronate?

Alendronate is used for treating osteoporosis in men and postmenopausal women. It also is used for Paget's disease of bone and osteoporosis caused by steroid treatment. Non-FDA approved (off-label) uses include vitamin D overdose and osteoporosis caused by spinal injury.

Alendronate Usage

  • Take alendronate exactly as your doctor tells you.
  • Alendronate works only if taken on an empty stomach.
  • Take alendronate after you get up for the day and before taking your first food, drink, or other medicine.
  • Take alendronate while you are sitting or standing.
  • Do not chew or suck on a tablet of alendronate.
  • Do not take alendronate with mineral water, coffee, tea, soda, or juice.
  • If you take alendronate daily:
    • Take 1 alendronate tablet one time a day, every day after you get up for the day and before taking your first food, drink, or other medicine.
  • If you take alendronate once weekly:
    • Choose the day of the week that best fits your schedule.
    • Tablets:
      • Take 1 dose of alendronate every week with water on your chosen day after you get up for the day and before taking your first food, drink, or other medicine.
    • Oral Solution:
      • Drink your prescribed dose every week on your chosen day after you get up for the day and before taking your first food, drink, or other medicine.
      • Drink at least 2 ounces of plain water after you drink alendronate oral solution.
    • Effervescent tablet:
      • Dissolve one tablet of alendronate in approximately half a glass of plain room temperature water (4 oz). Wait at least 5 minutes after the effervescence stops, stir the solution for approximately 10 seconds and drink the solution.
  • After swallowing alendronate tablet, wait at least 30 minutes:
    • Before you lie down. You may sit, stand or walk, and do normal activities like reading.
    • Before you take your first food or drink except for plain water.
    • Before you take other medicines, including antacids, calcium, and other supplements and vitamins.
  • Do not lie down for at least 30 minutes after you take alendronate and after you eat your first food of the day.
  • If you miss a dose of alendronate, do not take it later in the day. Take your missed dose on the next morning after you remember and then return to your normal schedule. Do not take 2 doses on the same day.
  • If you take too much alendronate, call your doctor. Do not try to vomit. Do not lie down.

Alendronate side effects

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using alendronate and call your doctor at once if you have:

  • chest pain, new or worsening heartburn;

  • difficulty or pain when swallowing;

  • pain or burning under the ribs or in the back;

  • severe heartburn, burning pain in your upper stomach, or coughing up blood;

  • new or worsening heartburn;

  • severe joint, bone, or muscle pain, new or unusual pain in your thigh or hip;

  • fever, body aches, flu symptoms; or

  • jaw pain, numbness, or swelling.

  • new or unusual pain in your thigh or hip;

Common side effects may include:

  • heartburn, upset stomach;

  • stomach pain, nausea;

  • diarrhea, constipation; or

  • bone pain, muscle or joint pain.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Commonly used brand name(s)

In the U.S.

  • Fosamax

Available Dosage Forms:

  • Tablet
  • Solution
  • Tablet, Effervescent

Therapeutic Class: Calcium Regulator

Chemical Class: Bisphosphonate

Precautions While Using alendronate

If you will be taking alendronate for a long time, it is very important that your doctor check your progress at regular visits to make sure alendronate is working properly and watch for unwanted effects.

alendronate can irritate your esophagus. If you think alendronate has started to damage your esophagus, stop taking alendronate and call your doctor. Some symptoms of damage to the esophagus are heartburn (either new or worse than usual), pain when swallowing, pain in the center of your chest, trouble swallowing, or feeling that food gets stuck on the way to your stomach.

It is important that you tell all of your health care providers that you are taking alendronate. If you are having a dental procedure while taking alendronate, you may have an increased chance of having a severe problem with your jaw.

Make sure you tell your doctor about any new medical problems, especially with your teeth or jaws. Tell your doctor if you have severe bone, joint, or muscle pain while using alendronate.

alendronate could lower the amount of calcium in your blood. Call your doctor right away if you develop any signs of low calcium levels, such as muscle spasms or twitching, or numbness or tingling in your fingers, toes, or lips.

alendronate may increase your risk of developing fractures of the thigh bone. This may be more common if you use it for a long time. Check with your doctor right away if you have a dull or aching pain in the thighs, groin, or hips.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Adverse Reactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Treatment of Osteoporosis in Postmenopausal Women
Daily Dosing
The safety of Alendronate sodium in the treatment of postmenopausal osteoporosis was assessed in four clinical trials that enrolled 7453 women aged 44-84 years. Study 1 and Study 2 were identically designed, three-year, placebo-controlled, double-blind, multicenter studies (United States and Multinational n=994); Study 3 was the three-year vertebral fracture cohort of the Fracture Intervention Trial [FIT] (n=2027) and Study 4 was the four-year clinical fracture cohort of FIT (n=4432). Overall, 3620 patients were exposed to placebo and 3432 patients exposed to Alendronate sodium. Patients with pre-existing gastrointestinal disease and concomitant use of non-steroidal anti-inflammatory drugs were included in these clinical trials. In Study 1 and Study 2 all women received 500 mg elemental calcium as carbonate. In Study 3 and Study 4 all women with dietary calcium intake less than 1000 mg per day received 500 mg calcium and 250 international units  Vitamin D per day.

Among patients treated with Alendronate 10 mg or placebo in Study 1 and Study 2, and all patients in Study 3 and Study 4, the incidence of all-cause mortality was 1.8% in the placebo group and 1.8% in the Alendronate sodium group. The incidence of serious adverse event was 30.7% in the placebo group and 30.9% in the Alendronate sodium group. The percentage of patients who discontinued the study due to any clinical adverse event was 9.5% in the placebo group and 8.9% in the Alendronate sodium group. Adverse reactions from these studies considered by the investigators as possibly, probably, or definitely drug related in greater than or equal to 1% of patients treated with either Alendronate sodium or placebo are presented in Table 1.

Table 1: Osteoporosis Treatment Studies in Postmenopausal Women Adverse Reactions Considered Possibly, Probably, or Definitely Drug Related by the Investigators and Reported in Greater Than or Equal to 1% of Patients
            United States/      
Multinational Studies
  Fracture
Intervention Trial
     Alendronate Sodium*
%
(n=196)
  Placebo
%
(n=397)
  Alendronate Sodium†
%
(n=3236)
  Placebo
%
(n=3223)
  Gastrointestinal            
     abdominal pain   6.6   4.8   1.5   1.5
     nausea   3.6   4.0   1.1   1.5
     dyspepsia   3.6   3.5   1.1   1.2
     constipation   3.1   1.8   0.0   0.2
     diarrhea   3.1   1.8   0.6   0.3
     flatulence   2.6   0.5   0.2   0.3
     acid regurgitation   2.0   4.3   1.1   0.9
     esophageal ulcer   1.5   0.0   0.1   0.1
     vomiting   1.0   1.5   0.2   0.3
     dysphagia   1.0   0.0   0.1   0.1
     abdominal distention   1.0   0.8   0.0   0.0
     gastritis   0.5   1.3   0.6   0.7
  Musculoskeletal            
     musculoskeletal (bone, muscle or joint) pain   4.1   2.5   0.4   0.3
     muscle cramp   0.0   1.0   0.2   0.1
  Nervous System/Psychiatric            
     headache   2.6   1.5   0.2   0.2
     dizziness   0.0   1.0   0.0   0.1
  Special Senses            
     taste perversion   0.5   1.0   0.1   0.0

* 10 mg/day for three years
† 5 mg/day for 2 years and 10 mg/day for either 1 or 2 additional years

Rash and erythema have occurred.  

Gastrointestinal Adverse Reactions: One patient treated with Alendronate (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. In the Study 1 and Study 2 populations, 49-54% had a history of gastrointestinal disorders at baseline and 54-89% used nonsteroidal anti-inflammatory drugs or aspirin at some time during the studies. [See Warnings and Precautions (5.1).]

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 less than 8.0 mg/dL (2.0 mM) and serum phosphate to less than or equal to 2.0 mg/dL (0.65 mM) were similar in both treatment groups.

Weekly Dosing
The safety of Alendronate 70 mg once weekly for the treatment of postmenopausal osteoporosis was assessed in a one-year, double-blind, multicenter study comparing Alendronate 70 mg once weekly and Alendronate 10 mg daily. The overall safety and tolerability profiles of once weekly Alendronate 70 mg and Alendronate 10 mg daily were similar. The adverse reactions considered by the investigators as possibly, probably, or definitely drug related in greater than or equal to 1% of patients in either treatment group are presented in Table 2.

Table 2: Osteoporosis Treatment Studies in Postmenopausal Women Adverse Reactions Considered Possibly, Probably, or Definitely Drug Related by the Investigators and Reported in Greater Than or Equal to 1% of Patients
     Once Weekly
Alendronate
70 mg
%
(n=519)
  Alendronate
10 mg/day
%
(n=370)
  Gastrointestinal      
         abdominal pain   3.7   3.0
         dyspepsia   2.7   2.2
         acid regurgitation   1.9   2.4
         nausea   1.9   2.4
         abdominal distention   1.0   1.4
         constipation   0.8   1.6
         flatulence   0.4   1.6
         gastritis   0.2   1.1
         gastric ulcer   0.0   1.1
  Musculoskeletal      
         musculoskeletal (bone, muscle, joint) pain   2.9   3.2
         muscle cramp   0.2   1.1

Prevention of Osteoporosis in Postmenopausal Women
Daily Dosing
The safety of Alendronate 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 5 mg/day and placebo were similar. Discontinuation of therapy due to any clinical adverse event occurred in 7.5% of 642 patients treated with Alendronate 5 mg/day and 5.7% of 648 patients treated with placebo. 

Weekly Dosing
The safety of Alendronate 35 mg once weekly compared to Alendronate 5 mg daily was evaluated in a one-year, double-blind, multicenter study of 723 patients. The overall safety and tolerability profiles of once weekly Alendronate 35 mg and Alendronate 5 mg daily were similar.

The adverse reactions from these studies considered by the investigators as possibly, probably, or definitely drug related in greater than or equal to 1% of patients treated with either once weekly Alendronate 35 mg, Alendronate 5 mg/day or placebo are presented in Table 3.

Table 3: Osteoporosis Prevention Studies in Postmenopausal Women Adverse Reactions Considered Possibly, Probably, or Definitely Drug Related by the Investigators and Reported in Greater Than or Equal to 1% of Patients
     Two/Three-Year Studies   One-Year Study
     Alendronate 
5 mg/day
%
(n=642)
  Placebo
%
(n=648)
  Alendronate 
5 mg/day
%
(n=361)
  Once Weekly
Alendronate 
35 mg
%
(n=362)
  Gastrointestinal            
     dyspepsia   1.9   1.4   2.2   1.7
     abdominal pain   1.7   3.4   4.2   2.2
     acid regurgitation   1.4   2.5   4.2   4.7
     nausea   1.4   1.4   2.5   1.4
     diarrhea   1.1   1.7   1.1   0.6
     constipation   0.9   0.5   1.7   0.3
    abdominal distention   0.2   0.3   1.4   1.1
  Musculoskeletal            
     musculoskeletal (bone, muscle or joint) pain   0.8   0.9   1.9   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 10 mg once daily and estrogen ± progestin (n=354) was consistent with those of the individual treatments. 

Osteoporosis in Men
In two placebo-controlled, double-blind, multicenter studies in men (a two-year study of Alendronate 10 mg/day and a one-year study of once weekly Alendronate 70 mg) the rates of discontinuation of therapy due to any clinical adverse event were 2.7% for Alendronate 10 mg/day vs. 10.5% for placebo, and 6.4% for once weekly Alendronate 70 mg vs. 8.6% for placebo. The adverse reactions considered by the investigators as possibly, probably, or definitely drug related in greater than or equal to 2% of patients treated with either Alendronate or placebo are presented in Table 4.

Table 4: Osteoporosis Studies in Men Adverse Reactions Considered Possibly, Probably, or Definitely Drug Related by the Investigators and Reported in Greater Than or Equal to 2% of Patients
     Two-year Study   One-year Study
     Alendronate 
10 mg/day
%
(n=146)
  Placebo
%
(n=95)
  Once Weekly
Alendronate
70 mg
%
(n=109)
  Placebo
%
(n=58)
  Gastrointestinal            
      acid regurgitation   4.1   3.2   0.0   0.0
      flatulence   4.1   1.1   0.0   0.0
      gastroesophageal reflux disease   0.7   3.2   2.8   0.0
      dyspepsia   3.4   0.0   2.8   1.7
      diarrhea   1.4   1.1   2.8   0.0
      abdominal pain   2.1   1.1   0.9   3.4
      nausea   2.1   0.0   0.0   0.0

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 5 and 10 mg/day were generally similar to that of placebo. The adverse reactions considered by the investigators as possibly, probably, or definitely drug related in greater than or equal to 1% of patients treated with either Alendronate 5 or 10 mg/day or placebo are presented in Table 5.

Table 5: One-Year Studies in Glucocorticoid-Treated Patients Adverse Reactions Considered Possibly, Probably, or Definitely Drug Related by the Investigators and Reported in Greater Than or Equal to 1% of Patients
     Alendronate 
10 mg/day
%
(n=157)
  Alendronate
5 mg/day
%
(n=161)
  Placebo
%
(n=159)
  Gastrointestinal         
         abdominal pain   3.2   1.9   0.0
         acid regurgitation   2.5   1.9   1.3
         constipation   1.3   0.6   0.0
         melena   1.3   0.0   0.0
         nausea   0.6   1.2   0.6
         diarrhea   0.0   0.0   1.3
  Nervous System/Psychiatric         
         headache   0.6   0.0   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 events reported in 175 patients taking Alendronate 40 mg/day for 3 to 12 months were similar to those in postmenopausal women treated with Alendronate 10 mg/day. However, there was an apparent increased incidence of upper gastrointestinal adverse reactions in patients taking Alendronate 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 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 events occurred in 6.4% of patients with Paget's disease treated with Alendronate 40 mg/day and 2.4% of patients treated with placebo.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Alendronate sodium. 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. 

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

Gastrointestinal: esophagitis, esophageal erosions, esophageal ulcers, esophageal stricture or perforation, and oropharyngeal ulceration. Gastric or duodenal ulcers, some severe and with complications, have also been reported [see Dosage and Administration (2.6); Warnings and Precautions (5.1)].

Localized osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection with delayed healing, has been reported [see Warnings and Precautions (5.4)].

Musculoskeletal: bone, joint, and/or muscle pain, occasionally severe, and incapacitating [see Warnings and Precautions (5.3)]; joint swelling; low-energy femoral shaft and subtrochanteric fractures [see Warnings and Precautions (5.5)].

Nervous System: dizziness and vertigo.

Pulmonary: acute asthma exacerbations.  

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

Special Senses: uveitis, scleritis or episcleritis. Cholesteatoma of the external auditory canal (focal osteonecrosis).

Alendronate Description

Alendronate sodium is a bisphosphonate that acts as a specific inhibitor of osteoclast­-mediated bone resorption. Bisphosphonates are synthetic analogs of pyrophosphate that bind to the hydroxyapatite found in bone.

Alendronate sodium is chemically described as (4-amino-1-hydroxybutylidene) bisphosphonic acid monosodium salt trihydrate.

The empirical formula of Alendronate sodium is C4H12NNaO7P2•3H2O and its formula weight is 325.12. The structural formula is:

Alendronate sodium is a white, crystalline, nonhygroscopic powder. It is soluble in water, very slightly soluble in alcohol, and practically insoluble in chloroform.

Alendronate sodium tablets, USP, for oral administration contain 45.68 mg or 91.37 mg of Alendronate monosodium salt trihydrate, which is the molar equivalent of 35 mg and 70 mg, respectively, of free acid, and the following inactive ingredients: microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, and magnesium stearate. This product meets USP Dissolution Test 2.

How Supplied/Storage and Handling

How Supplied
Alendronate sodium tablets, USP, 35 mg - white to off-white oval tablet embossed with “AN35" on one side and “” on the other side. They are supplied as follows:

NDC # 53217-0321-01   Unit-of-use Blister Package of 4

Storage
Alendronate Sodium Tablets:
Store at 20° to 25ºC (68° to 77ºF); excursions permitted to 15° to 30ºC (59° to 86ºF) [See USP Controlled Room Temperature].

Repackaged by:

Aidarex Pharmaceuticals, LLC

Corona, CA 92880

Pronunciation

(a LEN droe nate)

Pharmacology

A bisphosphonate which inhibits bone resorption via actions on osteoclasts or on osteoclast precursors; decreases the rate of bone resorption, leading to an indirect increase in bone mineral density. In Paget's disease, characterized by disordered resorption and formation of bone, inhibition of resorption leads to an indirect decrease in bone formation; but the newly-formed bone has a more normal architecture.

Distribution

28 L (exclusive of bone)

Metabolism

None

Excretion

Urine; feces (as unabsorbed drug)

Half-Life Elimination

Exceeds 10 years

Protein Binding

~78%

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, constipation, or diarrhea. Have patient report immediately to prescriber signs of low calcium (muscle cramps or spasms, numbness and tingling, or seizures); black, tarry, or bloody stools; angina; coughing up blood; severe abdominal pain; heartburn; difficulty swallowing; pain when swallowing; pharyngitis; severe nausea; severe vomiting; vomiting blood; severe bone pain; severe joint pain; severe muscle pain; groin, hip, or thigh pain; mouth sores; or jaw pain, or edema (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Adverse Effects

>10%

Hypocalcemia, transient and mild (18%)

1-10%

Hypophosphatemia, transient and mild (10%)

Abdominal pain (7%)

Musculoskeletal pain (4.1%)

Dyspepsia (3.6%)

Nausea (3.6%)

Constipation (3.1%)

Diarrhea (3.1%)

Flatulence (2.6%)

Headache (2.6%)

Acid regurgitation (2%)

Esophagitis (1.5%)

Abdominal distention (1%)

<1%

Alopecia

Diaphyseal femur fracture

Esophageal cancer

Flulike syndrome

Gastritis

Myalgia

Oropharyngeal ulceration

Pruritus

Rash

Taste perversion

Toxic epidermal necrolysis

Uveitis

Vertigo

Weakness

Postmarketing Reports

Body as a whole: Hypersensitivity reactions including urticaria and angioedema; transient myalgia, malaise, asthenia, and fever; symptomatic hypocalcemia; peripheral edema

Gastrointestinal: Esophagitis, esophageal erosions, esophageal ulcers, esophageal stricture or perforation, and oropharyngeal ulceration; gastric or duodenal ulcers

Localized osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection with delayed healing

Musculoskeletal: Bone, joint, and/or muscle pain, occasionally severe, and incapacitating; joint swelling; low-energy femoral shaft and subtrochanteric fractures

Nervous system: dizziness, vertigo

Pulmonary: Acute asthma exacerbations

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

Special Senses: Uveitis, scleritis, or episcleritis, cholesteatoma of the external auditory canal (focal osteonecrosis)

Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Abdominal pain, bone muscle or joint pain, dyspepsia, hair loss, itch, constipation, diarrhea, flatulence, dizziness, headache, vertigo, and swelling of the ankles or feet are the most common side effects.
  • Alendronate, like other bisphosphonates, may cause irritation of the esophagus and stomach. Some cases have been severe enough to warrant hospitalization. The risk is greater in people who lie down soon after taking alendronate or who don't take it with a full glass of water. Take exactly as directed.
  • Severe bone, joint, or muscle pain, necessitating discontinuation of alendronate in some people, has been reported, occurring from one day to several months after starting the drug.
  • Rarely may cause other side effects including uveitis (eye inflammation).
  • May not be suitable for some people including those with kidney disease, pre-existing esophageal conditions, low blood calcium levels (hypocalcemia), or who are unable to stand or sit upright for at least 30 minutes.
  • There are concerns about the long-term safety of bisphosphonates as long-term use has been associated with atypical femur fractures, osteonecrosis of the jaw and esophageal cancer.
  • Fracture risk reduction may also persist for years after treatment has stopped. The optimal duration of therapy with alendronate has not been established. Periodically re-evaluate the need for therapy. Discontinuation of therapy should be considered by doctors after 3 to 5 years in patients at low risk of fracture.

Notes: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. For a complete list of all side effects, click here.

Bottom Line

Alendronate helps to reduce the risk of fracture in people with osteoporosis and some other bone conditions. Dosage instructions, including remaining upright for at least 30 minutes and taking with a full glass of water, must be strictly followed. The optimal length of therapy remains unknown.

Alendronate Pregnancy Warnings

Reproduction studies in rats showed decreased postimplantation survival and decreased body weight gain in normal pups at less than half of the clinical recommended doses. Sites of incomplete fetal ossification were increased in rats at approximately 3 times the clinical dose in vertebral (cervical, thoracic, lumbar), skull, and sternebral bone. Both total and ionized calcium decreased in pregnant rats at approximately 4 times the clinical recommended dose, resulting in delays and failures of delivery. Maternotoxicty (late pregnancy deaths) also occurred in rats treated at approximately 4 times the clinical dose for varying periods of time (from only during pre-mating to treatment to only during early, middle or late pregnancy); these deaths were lessened but not eliminated by cessation of treatment. In studies with pregnant rats, oral alendronate doses of 2 mg/kg/day and above resulted in dystocia due to maternal hypocalcemia. Fetal weight was reduced in rats at maternal doses greater than 5 mg/kg/day. No teratogenic effects were seen in rats or rabbits at oral doses up to 25 and 35 mg/kg/day, respectively. Calcium supplementation either in the drinking water or by minipump may not ameliorate the hypocalcemia or prevent maternal and neonatal deaths due to delay in delivery; IV calcium supplementation prevented maternal, but not fetal deaths. There are no controlled data on fetal risk in humans or in human pregnancy. AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

AU, UK: Use should be avoided. US: This drug should not be used during pregnancy unless the benefit outweighs the risk to the fetus. AU TGA pregnancy category: B3 US FDA pregnancy category: C Comment: There is theoretical risk of fetal harm, predominantly skeletal, if pregnancy occurs after completing a course of bisphosphonates therapy.

Alendronate Breastfeeding Warnings

AU, UK: Use should be avoided. US: Caution is recommended. Excreted into human milk: Unknown Excreted into animal milk: Data not available Comments: The effects in the nursing infant are unknown.

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