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Didronel
Classes
Injectable Bisphosphonates
Oral Bisphosphonates
Administration
Administer on an empty stomach with a 180 to 240 mL glass of water.
Patients should avoid eating for at least 2 hours before and after administration of an etidronate dose; food decreases absorption.
Patients should not take vitamin with mineral supplements or antacids containing calcium, iron, magnesium, or aluminum within 2 hours of etidronate dosing.
Patients should not lie down after taking this medication.
The dose may be divided if GI discomfort occurs with a single oral dose.
Ensure adequate intake of calcium and vitamin D to reduce the risk of treatment-related hypocalcemia.
Etidronate injection is discontinued in the U.S. The intravenous drug was administered as an intravenous infusion after dilution.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Dilution:
Dilute in at least 250 mL of sterile 0.9% Sodium Chloride injection; volumes greater than 250 mL may be used if convenient.
Doses of 25 and 30 mg/kg/day have been administered as a single 24-hour IV infusion and must be diluted in at least 1000 mL of sterile 0.9% Sodium Chloride injection.
Diluted solution is stable for 48 hours.
Intravenous infusion:
Infuse recommended daily dose IV over at least 2 hours. Doses of 25 and 30 mg/kg/day have been administered as a single 24-hour IV infusion.
Adverse Reactions
atrial fibrillation / Early / Incidence not known
agranulocytosis / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
esophageal stricture / Delayed / Incidence not known
peptic ulcer / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
GI perforation / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
odynophagia / Delayed / Incidence not known
esophageal ulceration / Delayed / Incidence not known
azotemia / Delayed / Incidence not known
anuria / Delayed / Incidence not known
bone fractures / Delayed / Incidence not known
visual impairment / Early / Incidence not known
uveitis / Delayed / Incidence not known
osteonecrosis / Delayed / Incidence not known
bone pain / Delayed / 10.0
gastritis / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
depression / Delayed / Incidence not known
confusion / Early / Incidence not known
amnesia / Delayed / Incidence not known
esophagitis / Delayed / Incidence not known
osteomalacia / Delayed / Incidence not known
glossitis / Early / Incidence not known
hallucinations / Early / Incidence not known
dysphagia / Delayed / Incidence not known
colitis / Delayed / Incidence not known
hyperphosphatemia / Delayed / Incidence not known
ocular inflammation / Early / Incidence not known
conjunctivitis / Delayed / Incidence not known
nausea / Early / 10.0
diarrhea / Early / 10.0
metallic taste / Early / Incidence not known
dysgeusia / Early / Incidence not known
headache / Early / Incidence not known
pyrosis (heartburn) / Early / Incidence not known
vomiting / Early / Incidence not known
paresthesias / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
alopecia / Delayed / Incidence not known
maculopapular rash / Early / Incidence not known
urticaria / Rapid / Incidence not known
arthralgia / Delayed / Incidence not known
muscle cramps / Delayed / Incidence not known
myalgia / Early / Incidence not known
musculoskeletal pain / Early / Incidence not known
arthropathy / Delayed / Incidence not known
ocular pain / Early / Incidence not known
Common Brand Names
Didronel
Dea Class
Rx
Description
Injectable and oral first-generation bisphosphonate with a lower potency and selectivity vs. newer second- and third-generation bisphosphonates
For Paget's disease the drug has largely been replaced by newer bisphosphonates that are easier to use and have greater antiresorptive potency; also indicated for heterotopic ossification but treatment is costly
Not recommended by guidelines for osteoporosis treatment or prevention as lacks efficacy data proving fracture reduction
Dosage And Indications
5 to 10 mg/kg/day PO for no longer than 6 months or 11 to 20 mg/kg/day PO for no longer than 3 months. Reserve doses of more than 10 mg/kg/day for when lower doses are ineffective or when a rapid response is needed. Max: 20 mg/kg/day PO. Monitor patients every 3 to 6 months; however, some patients may go drug-free for extended periods. Retreat only after 1) an etidronate-free period of at least 90 days, and 2) if there is biochemical, symptomatic or other evidence of active disease. Retreatment regimens are the same as for initial treatment; the original dose is adequate for most patients.[28655] In Paget's disease, etidronate therapy has largely been replaced by newer bisphosphonates (e.g., zoledronic acid) that are easier to use and have greater antiresorptive potency relative to their inhibition of mineralization.
20 mg/kg PO once daily for 2 weeks, followed by 10 mg/kg PO once daily for an additional period of 10 weeks. Retreatment has not been studied.
Safety and efficacy have not been established; however, the adult dosage for this condition has been used in children. A rachitic syndrome has been reported infrequently at doses of 10 mg/kg/day and more for prolonged periods approaching or exceeding a year.[28655]
20 mg/kg PO once daily administered preoperatively for 1 month, followed by 20 mg/kg PO once daily postoperatively for a 3 month period. Retreatment has not been studied.
Safety and efficacy have not been established; however, the adult dosage for this condition has been used in children. A rachitic syndrome has been reported infrequently at doses of 10 mg/kg/day and more for prolonged periods approaching or exceeding a year.[28655]
This drug is discontinued in the U.S. The usual dose was 7.5 mg/kg IV infusion once daily, administered for 3 consecutive days. Etidronate was designated an orphan drug by the FDA for this indication; however, etidronate therapy has been replaced with more potent bisphosphonates for this condition.
Dosing Considerations
No dosage adjustment is necessary in patients with hepatic impairment; the drug is not metabolized.
Etidronate disodium dosage should be reduced in patients with renal impairment based on the reduction in glomerular filtration rate (GFR), but specific dosage reduction recommendations are not available. Patients with renal impairment should be closely monitored.
Drug Interactions
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Acetaminophen; Aspirin: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aluminum Hydroxide: (Moderate) Separate administration of oral etidronate and aluminum hydroxide by at least 2 hours. Aluminum-containing antacids will interfere with the absorption of oral etidronate.
Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Separate administration of oral etidronate and aluminum hydroxide by at least 2 hours. Aluminum-containing antacids will interfere with the absorption of oral etidronate.
Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Separate administration of oral etidronate and aluminum hydroxide by at least 2 hours. Aluminum-containing antacids will interfere with the absorption of oral etidronate.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Separate administration of oral etidronate and aluminum hydroxide by at least 2 hours. Aluminum-containing antacids will interfere with the absorption of oral etidronate.
Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Separate administration of oral etidronate and aluminum hydroxide by at least 2 hours. Aluminum-containing antacids will interfere with the absorption of oral etidronate.
Aspirin, ASA: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Caffeine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Carisoprodol: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Carisoprodol; Codeine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product. (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Dipyridamole: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Omeprazole: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Aspirin, ASA; Oxycodone: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Butalbital; Aspirin; Caffeine; Codeine: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and aspirin. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Calcium (oral): (Moderate) Separate administration of oral etidronate and calcium-containing supplements by at least 2 hours. Calcium will interfere with the absorption of oral etidronate.
Food: (Major) Food decreases the bioavailability of risedronate, and may also increase the risk of esophageal irritation from the medication. Take risedronate at least 30 minutes before their first food or drink of the day, other than plain water.
Iron: (Moderate) Separate administration of oral etidronate and iron supplements by at least 2 hours. Iron will interfere with the absorption of oral etidronate.
Lanthanum Carbonate: (Moderate) To limit absorption problems, the oral bisphosphonates should not be taken within 2 hours of dosing with lanthanum carbonate. Oral drugs known to interact with cationic antacids, like the oral bisphosphonates, may also be bound by lanthanum carbonate. Separating times of administration will maximize absorption and clinical benefit of the bisphosphonate. Separate the times of administration appropriately. Monitor the patient's clinical status and bone density as recommended to ensure the appropriate response to bisphosphonate therapy is obtained.
Magnesium Citrate: (Moderate) Do not administer oral magnesium-containing products within 2 hours of oral bisphosphonates; oral magnesium may significantly reduce the absorption of the oral bisphosphonates (e.g., alendronate, etidronate, ibandronate, risedronate, or tiludronate). All medications should be administered at least 30 minutes after an alendronate or risedronate dose, and at least 1 hour after an ibandronate dose to help prevent absorption interactions. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after these drugs or at a different time of day.
Magnesium Salts: (Moderate) Do not administer any oral magnesium-containing products within 2 hours of etidronate; oral magnesium may significantly reduce the absorption of etidronate. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after any oral bisphosphonates or at a completely different time of day.
Magnesium: (Moderate) Do not administer any oral magnesium-containing products within 2 hours of etidronate; oral magnesium may significantly reduce the absorption of etidronate. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after any oral bisphosphonates or at a completely different time of day.
Nonsteroidal antiinflammatory drugs: (Minor) Monitor for gastrointestinal adverse events during concurrent use of etidronate and nonsteroidal antiinflammatory drugs. Both medications have been associated with gastrointestinal irritation although data suggest concomitant use introduces little additional risk for adverse effects for most patients.
Omeprazole; Sodium Bicarbonate: (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product.
Polycarbophil: (Moderate) Coadministration of etidronate with calcium polycarbophil can interfere with the oral absorption of etidronate; do not administer calcium polycarbophil within 2 hours of etidronate. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg).
Sodium Bicarbonate: (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Moderate) Do not administer any oral magnesium-containing products within 2 hours of etidronate; oral magnesium may significantly reduce the absorption of etidronate. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after any oral bisphosphonates or at a completely different time of day.
Warfarin: (Moderate) There have been isolated reports of etidronate causing an increased prothrombin time/INR when the drug is given to patients stabilized on warfarin. Although none of the reports have described clinically significant sequelae, it is advisable to monitor the INR periodically in patients taking warfarin who have etidronate therapy added.
How Supplied
Didronel/Etidronate Disodium/Etidronic acid Oral Tab: 200mg, 400mg
Maximum Dosage
20 mg/kg/day PO.
20 mg/kg/day PO.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
Mechanism Of Action
Etidronate inhibits both bone resorption and bone mineralization. Like endogenous pyrophosphates and other bisphosphonates, etidronate binds tightly to hydroxyapatite crystals in mineralized bone matrix. However, unlike naturally occurring pyrophosphates, etidronate is resistant to pyrophosphatase degradation, the normal enzymatic metabolism of bone. Etidronate decreases normal and abnormal bone resorption; reducing bone turnover and slowing the remodeling process in both healthy and diseased bone. The binding of etidronate to calcium phosphates inhibits the formation and aggregation of hydroxyapatite crystals and slows the dissolution of these crystals. The inhibition of hydroxyapatite crystal formation may account for the inhibition of mineralization and growth observed following high doses of etidronate. This inhibition of mineralization is evident with prolonged, continuous treatment with etidronate, which may lead to impaired calcification of newly formed bone and osteomalacia. For this reason, etidronate is administered cyclically. Etidronate has no antineoplastic properties. When used for heterotopic ossification, etidronate will not inhibit the healing of spinal fractures in patients with spinal cord injury, and it will not affect the prosthesis or disrupt the trochanter attachment when used in patients with total hip arthroplasty.[50514]
Pharmacokinetics
Etidronate is administered orally and intravenously. Etidronate is distributed readily from the blood and concentrates in bone tissue. It is not clear if the drug crosses the placenta or distributes into breast milk. Etidronate is not metabolized and approximately 50% of the systemically available dose is excreted by the kidneys within 24 hours. The plasma elimination half-life has been shown to average 6 hours, with a mean residence time in an exchangeable pool of about 8.7 hours. Animal studies suggest that the retention half-life of the drug in bone is 3—6 months.
Etidronate is absorbed erratically and poorly by the oral route. Oral bioavailability is approximately 3%. The extent of absorption can be decreased in the presence of foods. Unabsorbed drug is excreted intact in the feces.
Pregnancy And Lactation
There are no studies of etidronate use during pregnancy. It is prudent to avoid using etidronate during pregnancy unless the potential benefit to the mother justifies any possible risk to the fetus.[28655] Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over a period of years. The amount of bisphosphonate incorporated into adult bone, and hence, the amount available for release back into the systemic circulation, is directly related to the dose and duration of bisphosphonate use. There are no data on fetal risk in humans. However, there is a theoretical risk of fetal harm (predominantly skeletal) if a woman becomes pregnant after completing a course of bisphosphonate therapy. The impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on the risk has not been studied. Bisphosphonates do cause fetal harm (predominantly skeletal) in animals, suggesting the uptake of bisphosphonates into fetal bone is greater than into maternal bone. Animal reproductive studies indicate etidronate causes multiple fetal abnormalities in rat and rabbit offspring as well as maternal toxicity, including decreased body weight, protracted parturition due to maternal hypocalcemia, and maternal death.[28655] A single case reports the use of 2 doses of etidronate administered directly to a fetus via percutaneous injection into the umbilical vein during week 28 of gestation; the infant was diagnosed with idiopathic arterial calcification of infancy. One week later, the infant was born (29 weeks gestation) because of fetal distress. The infant continued to receive etidronate for several months after birth but died at 7.5 months of life despite aggressive medical care. As detected via X-rays during treatment with etidronate, the infant had severe growth plate malformations (mimicking rickets) that may have been caused by continued etidronate therapy; the data could not indicate that the fetal distress/prematurity was caused by etidronate.[32896]
Use etidronate with caution during breast-feeding. It is not known whether this drug is excreted in human milk. There are no data regarding the effect of the drug on the breastfed infant or breastmilk composition. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.