Etidronate (Etibon) is a bisphosphonate that takes calcium from the blood to the bones. It is used to treat patients with Paget's disease, osteoporosis, and other conditions resulting in hypercalcemia such as multiple myeloma.

Etidronate (Etibon) Uses:

• Paget disease:

  • It is the symptomatic treatment of Paget disease of bone

• Heterotopic ossification:

  • It is the prevention and treatment of heterotopic ossification due to spinal cord injury or after total hip replacement.

Etidronate (Etibon) Dose in Adults

If dietary intake is inadequate patients should receive supplemental calcium and vitamin D.

Etidronate (Etibon) Dose in the treatment of Paget disease: Oral:

• Initial: 5 to 10 mg/kg/day (never  exceed it to 6 months) or 11 to 20 mg/kg/day (not to exceed it to  3 months).
• The recommended initial dose is 5 mg/kg/day (never exceed it to 6 months).
• Doses more than 10 mg/kg/day should be used only when lower doses are ineffective or there is a need to suppress rapid bone turnover (ie, the potential for irreversible neurologic damage) or reduce elevated cardiac output.
• Doses of more than 20 mg/kg/day are not recommended.

• Re-treatment:

  • Initiate only after an etidronate-free period of 90 days or more than 90 days. Monitor patients every 3 to 6 months.
  • Re-treatment regimens are the same as for initial treatment. In cases where the original dose is not adequate, consider increasing the dose within the recommended guidelines.

Etidronate (Etibon) Dose in the treatment of Heterotopic ossification: Oral:

• Caused by spinal cord injury:

  • 20 mg/kg/day for 2 weeks, then 10 mg/kg/day for 10 weeks; total treatment period: 12 weeks

• Complicating total hip replacement:

  • 20 mg/kg/day for 1 month preoperatively then 20 mg/kg/day for 3 months postoperatively; total treatment period is 4 months
  • Re-treatment: Has not been studied.

Etidronate (Etibon) Dose in Childrens

Etidronate (Etibon) Dose in the treatment of Heterotopic ossification, traumatic brain injury: 

• Children and Adolescents:

  • Oral: Initial: 20 mg/kg/dose for 2 to 4 weeks once in a day, then decrease to 10 mg/kg/dose for 12 weeks to 1 year once in a day.

Pregnancy Risk Factor: C

• In some studies on animal reproduction, adverse events were reported.
• Although it is not clear if bisphosphonates cross into the placenta or not, it is possible that fetal exposure may occur.
• Bisphosphonates are integrated into bone matrix and slowly released over time.
• Doses and length of therapy affect the amount of systemic circulation.
• Theoretically, there could be a risk to fetal harm if a treatment is completed during pregnancy. However, data do not support this claim.
• Bisphosphonate therapy should be stopped in women of reproductive potential before a planned pregnancy.
• Premenopausal women should only be used in exceptional circumstances where rapid bone loss is happening.
• Hypocalcemia has been reported in infants exposed to in utero bisphosphonate. Therefore, it is important that hypocalcemia be checked after birth.

Etidronate use during breastfeeding:

• It is unknown if etidronate can be found in breast milk.
• The manufacturer suggests that nursing mothers exercise caution when giving etidronate.

Dose in Kidney Disease:

Manufacturer’s labeling recommends decreasing the dose when GFR is reduced; however, no specific dosage adjustments are provided. Use with caution and monitor closely; etidronate is eliminated intact via the kidneys. 

Dose in Liver disease:

In manufacturer's labeling no dosage adjustments are provided.

Side effects of Etidronate (Etibon):

• Gastrointestinal:

  • Nausea
  • Diarrhea

• Neuromuscular & skeletal:

  • Ostealgia

Contraindications to Etidronate (Etibon):

• Hypersensitivity to bisphosphonates and any component of the formulation
• Overt osteomalacia;
• Patients suffering from abnormalities of their esophagus (eg stricture, achalasia) that delay esophageal emptying.

Warnings and precautions

• Bone/ joint/ muscle pain:

  • The time it took to feel pain was anywhere from one day to several years.
  • Occasionally, severe and sometimes debilitating joint, bone, or muscle pain has been reported after bisphosphonate treatment.
  • Patients who have had recurrences with one bisphosphonate or another may experience them again.
  • Patients with severe symptoms should consider quitting therapy. Symptoms usually disappear once treatment is stopped.

• Fracture risk

  • Patients with Paget's disease should not exceed the recommended dosage or continue to use the medication for more than 6 months; there may be an increased risk of fractures or osteomalacia.
  • Patients who are not responsive to treatment may have long bones that are prone to breaking, especially if they have lytic lesions.

• Irritation of the gastrointestinal mucosa

  • It can cause irritation of the upper gastrointestinal mucosa.
  • Patients with dysphagia or esophageal diseases, gastritis, duodenitis, and ulcers should be cautious. This could worsen the condition.
  • Patients who are unable to follow dosing instructions may experience esophagitis, dysphagia and esophageal injuries.
  • If you experience new or worsening symptoms, stop using the medication.

• Osteonecrosis in the jaw:

  • MRONJ risk factors include invasive dental procedures (eg tooth extraction, boney procedure and dental implants), cancer diagnosis; concomitant radiotherapy, chemotherapy or corticosteroids; anemia.
  • Osteonecrosis (ONJ), also known as medication-related osteonecrosis (MRONJ) has been reported in patients who have received bisphosphonates.
  • It has been seen primarily in patients who had their teeth extracted and in cancer patients who were receiving IV bisphosphonates.
  • However, it has also been reported in patients with osteoporosis postmenopausal and patients who are receiving oral bisphosphonates.
  • A position paper from the American Association of Maxillofacial Surgeons states that MRONJ was associated with bisphosphonate (denosumab) and other antiresorptive drugs (denosumab) and antiangiogenic (e.g. sunitinib and bevacizumab), used to treat osteoporosis and malignancy.
  • According to the manufacturer's labeling, patients who require invasive dental procedures should discontinue bisphosphonates. Clinical judgment should be used to make this decision.
  • The AAOMS says that there is no evidence to suggest that stopping oral bisphosphonate treatment after a tooth is extracted increases the risk of ONJ.
  • It also suggests that patients who have been receiving oral bisphosphonate for less than four years and have not developed any clinical risk factors should undergo no delays or alternations in any procedure.
  • Special considerations are required for patients who receive dental implants.
  • Patients with ONJ should be seen by an oral surgeon during treatment.
  • An oral surgeon should be consulted for patients with ONJ.
  • Patients who have been receiving oral bisphosphonates more than four years, or patients who have taken antiangiogenic or corticosteroids concomitantly, should consider a 2-month drug-free period before undergoing invasive dental procedures. This recommendation is based on theoretical benefits.
  • According to the manufacturer of the bisphosphonate treatment, patients with ONJ should consider discontinuing it (based on the risk/benefit evaluation).

• Enterocolitis

  • Patients with enterocolitis should be cautious. High doses of diarrhea have been reported and may require treatment.

• Renal impairment

  • Patients with severe renal impairment should be cautious when using it.

Etidronate: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

Paget disease:

• Alkaline phosphatase at 6 to 12 weeks for initial response to treatment (when bone turnover will have shown a substantial decline) and potentially at 6 months (maximal suppression of high bone turnover);
• Following treatment completion, monitor at ~6- to 12-month's time period.
• Monitoring more specific biochemical markers of bone turnover (eg, NTX, serum P1NP, serum beta-CTx) is generally only warranted in patients with Paget disease who have abnormal liver or biliary tract function or when an early assessment of response to treatment is needed (eg, very active disease, spinal compression)
• Monitor for pain;
• Serum calcium and 25(OH) vitamin D.

How to administer Etidronate (Etibon)?

• Administer the tablet with a full glass of plain water (6 to 8 oz) 2 hours before food on an empty stomach.
• After taking the medication patients should be instructed to stay upright (not to lie down). If gastrointestinal discomfort occurs, the dose may be divided.

Mechanism of action of Etidronate (Etibon):

It reduces bone resorption through inhibiting osteocytic osteolysis.

The beginning of action:

• 1- 3 Months

Duration:

• Can persist for 12 months without continuous therapy

Absorption:

• ~3%

Metabolism:

• None

Half-life elimination:

• 1 to 6 hours

Excretion:

• Primarily urine (50% as unchanged drug);
• feces (as unabsorbed drug)

International Brand Names of Etidronate:

• Etibon
• Etidron
• Etidronat Jenapharm
• Etronel
• Oestrodidronel
• Osbone
• Ostedron
• Osteotop
• Osteum
• Yilin
• ACT Etidronate
• APO-Etidronate
• CO Etidronate
• MYLAN-Etidronate
• Bonatronil
• Dainol
• Didronat
• Didronate
• Didronel
• Difosfen
• Dinol
• Diosfen
• Diphos
• Disonate

Etidronate Brand Names in Pakistan: