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Didronel Side Effects

Generic Name: etidronate

Note: This page contains information about the side effects of etidronate. Some of the dosage forms included on this document may not apply to the brand name Didronel.

Not all side effects for Didronel may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to etidronate: oral tablet

In addition to its needed effects, some unwanted effects may be caused by etidronate (the active ingredient contained in Didronel). In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking etidronate:

More common
  • Bone pain or tenderness (increased, continuing, or returning—in patients with Paget's disease)
Less common
  • Bone fractures, especially of the thigh bone
  • Abdominal or stomach pain or burning
  • bloody, black, or tarry stools
  • chest pain
  • chills
  • cough or hoarseness
  • fever
  • general feeling of tiredness or weakness
  • hives
  • lower back or side pain
  • noisy breathing
  • painful or difficult urination
  • pale skin
  • skin rash or itching
  • sore throat
  • sores, ulcers, or white spots on the lips or inside the mouth
  • swelling of the arms, legs, face, lips, tongue, or throat
  • swollen glands
  • tightness in the chest
  • unusual bleeding or bruising
Incidence not known
  • Blistering, peeling, loosening of the skin
  • bone, joint, or muscle pain that is severe and occasionally disabling
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • difficulty in moving
  • difficulty in swallowing
  • discouragement
  • feeling sad or empty
  • heartburn
  • heavy jaw feeling
  • irritability
  • lack of appetite
  • large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
  • loosening of a tooth
  • loss of interest or pleasure
  • loss of memory
  • pain or burning in the throat
  • pain, swelling, or numbness in the mouth or jaw
  • problems with memory
  • rash with flat lesions or small raised lesions on the skin
  • red irritated eyes
  • red skin lesions, often with a purple center
  • redness or discoloration of the skin
  • seeing, hearing, or feeling things that are not there
  • trouble concentrating
  • trouble sleeping
  • unusual tiredness or weakness
  • vomiting

If any of the following symptoms of overdose occur while taking etidronate, get emergency help immediately:

Symptoms of overdose
  • Abdominal or stomach cramps
  • confusion
  • convulsions
  • difficulty in breathing
  • irregular heartbeats
  • mood or mental changes
  • muscle cramps in the hands, arms, feet, legs, or face
  • numbness and tingling around the mouth, fingertips, or feet
  • shortness of breath
  • tremor

Some of the side effects that can occur with etidronate may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common - at higher doses
  • Diarrhea
  • nausea
Incidence not known
  • Burning feeling in the chest or stomach
  • hair loss, thinning of hair
  • headache
  • indigestion
  • leg cramps
  • stomach upset
  • tenderness in the stomach area

For Healthcare Professionals

Applies to etidronate: intravenous solution, oral tablet


Etidronate has been generally well tolerated after both oral and intravenous administration. Side effects have been uncommon and appear to be dose related, usually occurring only with doses above 5 mg/kg per day. Because etidronate (the active ingredient contained in Didronel) undergoes renal elimination, patients with reduced renal function may accumulate drug and are, therefore, at increased risk for side effects.[Ref]


Etidronate use is associated with elevations in serum creatinine and BUN in up to 10% of patients. Patients with preexisting renal disease or on concomitant potentially renal toxic agents may be at increased risk. In addition, the use of higher than recommended doses or rapid infusion rates may contribute to the potential renal toxicity of etidronate (the active ingredient contained in Didronel) In animal studies, etidronate produced proximal renal tubular damage when used in high doses.

The risk of renal side effects may be reduced by delaying etidronate therapy until the patient is adequately volume expanded.[Ref]

Renal side effects have included mild to moderate increases in serum creatinine (0.5 mg/dl or more) as well as BUN in up to 10% of patients.[Ref]


Gastrointestinal side effects have included diarrhea, nausea, vomiting, abdominal discomfort, esophagitis, glossitis, and peptic ulcer. Loss of taste or metallic taste has been reported in up to 52% of patients receiving intravenous etidronate (the active ingredient contained in Didronel) and in 4% of patients receiving oral etidronate.[Ref]

Gastrointestinal side effects are more common with higher doses (10 to 20 mg/kg) and may be alleviated by dividing the daily dose. While these effects are generally mild and transient, perforated peptic ulcers, with or without subsequent peritonitis, have occurred. At least one fatality has been reported. Patients on high doses or unusually prolonged therapy may be at greater risk for severe gastrointestinal side effects of etidronate.[Ref]


Cardiovascular side effects have included a case report of mitral and aortic valve thickening; causality is unknown.[Ref]


Dermatologic side effects have included rash and pruritus. Alopecia has been reported in patients receiving etidronate (the active ingredient contained in Didronel) [Ref]


Hypersensitivity side effects have included rash, follicular eruptions, urticaria, and angioedema. A case of Stevens-Johnson Syndrome has been reported.[Ref]


Musculoskeletal side effects have included worsening of pagetic bone pain, arthralgias, fractures, and osteomalacia.[Ref]

Worsening of pagetic bone pain as well as appearance of pain at sites which were previously asymptomatic is reported in 10 to 20% of patients. This generally resolves despite continued therapy in most patients.

In one study, 9/13 patients with Paget's disease had biopsy evidence of focal osteomalacia after treatment with etidronate. All 13 patients had evidence of a mineralization defect. Two patients suffered fissure fractures.

Worsening pagetic pain and a rapid decline in serum alkaline phosphatase levels were reported in a patient who experienced a fractured patella associated with the development of osteomalacia. The authors suggest that worsened pagetic pain in association with a rapid decline in alkaline phosphatase may be a predictor of osteomalacia risk.[Ref]


Metabolic side effects have included hypocalcemia and hyperphosphatemia, although clinical manifestations are not noted.[Ref]


Psychiatric side effects have included amnesia, confusion, depression and hallucinations.[Ref]

Nervous system

Nervous system side effects have included paresthesia.[Ref]


Respiratory side effects have included rare exacerbation of asthma.[Ref]


Hematologic side effects have been rare, but have included agranulocytosis, pancytopenia, and a report of leukopenia with recurrence on rechallenge.[Ref]


1. Lourwood DL "The pharmacology and therapeutic utility of bisphosphonates." Pharmacotherapy 18 (1998): 779-89

2. "Product Information. Didronel Tablets (etidronate)." Procter and Gamble Pharmaceuticals, Cincinnati, OH.

3. "Product Information. Didronel I.V. Infusion (etidronate)." MGI Pharma Inc, Minnetonka, MN.

4. Saunders RL, Jr "Appearance of a gastric ulcer during diphosphonate therapy in a woman with CRST syndrome." South Med J 70 (1977): 1327-9

5. Beauchesne MF, Miller PF "Etidronate and alendronate in the treatment of postmenopausal osteoporosis." Ann Pharmacother 33 (1999): 587-99

6. Jaworski RC, Gibson M "Mitral and aortic valve abnormalities in a patient with fibrodysplasia ossificans progressiva." Pathology 15 (1983): 325-8

7. vanStaa TP, Leufkens H, Abenhaim L, Cooper C "Postmarketing surveillance of the safety of cyclic etidronate." Pharmacotherapy 18 (1998): 1121-8

8. Jones PB, McCloskey EV, Kanis JA "Transient taste-loss during treatment with etidronate ." Lancet 2 (1987): 637

9. Evans RA, MacDonald D "Diphosphonates and painful feet." Aust N Z J Med 13 (1983): 175-6

10. Evans RA, Dunstan CR, Hills E, Wong SY "Pathologic fracture due to severe osteomalacia following low-dose diphosphonate treatment of Paget's disease of bone." Aust N Z J Med 13 (1983): 277-9

11. Gallacher SJ, Boyle IT, Capell HA "Pseudogout associated with the use of cyclical etidronate therapy." Scott Med J 36 (1991): 49

12. Mautalen C, Gonzalez D, Blumenfeld EL, Santini Araujo E, Schajowicz F "Spontaneous fractures of uninvolved bones in patients with Paget's disease during unduly prolonged treatment with disodium etidronate (EHDP)." Clin Orthop Jun (1986): 150-5

13. Boyce BF, Smith L, Fogelman I, Johnston E, Ralston S, Boyle IT "Focal osteomalacia due to low-dose diphosphonate therapy in Paget's disease." Lancet 1 (1984): 821-4

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