Equidronate

Equidronate Uses, Dosage, Side Effects, Food Interaction and all others data.

Tiludronate, or (4-chlorophenyl)thio-methylene-1,1-bisphosphonate, is a first generation bisphosphonate similar to etidronic acid and clodronic acid. These drugs were developed to mimic the action of pyrophosphate, a regulator of calcification and decalcification. Equidronate was first described in the literature in 1988 as a potential treatment for Paget's disease of bone.

Equidronate was granted FDA approval on 7 March 1997.

Equidronate is a bisphosphonate that prevents osteoclasts from resorbing bone. The duration of action is quite long due to the slow clearance from the bone, and the therapeutic window is wide. Patients should be counselled regarding the risk of upper GI mucosal irritation as well as gastric and duodenal ulcers.

Equidronate
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Equidronate
Generic	Tiludronic acid
Tiludronic acid Other Names	Acide tiludronique, Acido tiludronico, Acidum tiludronicum, Tiludronate, Tiludronic acid
Type
Formula	C₇H₉ClO₆P₂S
Weight	Average: 318.608 Monoisotopic: 317.928359441
Protein binding	Tiludronic acid is approximately 90% protein bound in serum. It is mostly bound to albumin.
Groups	Approved, Investigational, Vet approved
Therapeutic Class
Manufacturer
Available Country	United Kingdom
Last Updated:	September 19, 2023 at 7:00 am

Uses

Equidronate is a bisphosphonate used for the treatment of Paget's disease of bone.

Equidronate is indicated to treat Paget's disease of bone in patients with serum alkaline phosphatase levels ≥2 times the upper limit of normal, with symptoms, or with risk of future complications.

Equidronate is also used to associated treatment for these conditions: Paget's Disease of Bone

How Equidronate works

Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis. Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act.

Osteoclasts mediate resorption of bone. When osteoclasts bind to bone they form podosomes, ring structures of F-actin. Tiludronate inhibits protein-tyrosine-phosphatase, which increases tyrosine phosphorylation, and disrupts podosome formation. Equidronate also inhibits V-ATPases in the osteoclast, though the exact subunits are unknown, preventing F-actin from forming podosomes. Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption.

Toxicity

Patients experiencing an overdose may present with hypocalcemia. Patients given doses of 6mg/kg/day for 2 days have experienced acute renal failure and death. Treat overdose with symptomatic and supportive care. Dialysis will not be useful for removal of the drug from serum.

Food Interaction

Take at least 2 hours before or after calcium supplements.
Take on an empty stomach. Take at least 2 hours before or after meals.
Take separate from antacids. Take at least 2 hours before or after antacids. The bioavailability of this medication is significantly reduced when administered with aluminum or magnesium containing antacids.
Take with a full glass of water.

Volume of Distribution

The volume of distribution of tiludronic acid is estimated to be between 30L and 60L. Due to the unknown clearance rate from bone, this may underestimate the true volume of distribution.

Elimination Route

A single 400mg dose of tiludronic acid reaches a C_max of 3.35±1.07mg/L, with a T_max of 1.7—0.9h, and and AUC of 27.2±9.0mg*h/L. Equidronate has an oral bioavailability of 2-11% with an average of 6%.

Half Life

The mean plasma elimination half-life is 150 hours, though the elimination rate from bone is unknown. The terminal phase half life is approximately 40h after a single IV dose of 10-30mg.

Clearance

Equidronate has a renal clearance of 0.68L/h in healthy subjects and 0.47L/h in subjects with Paget's disease. Approximately 50% of tilurdronic acid binds to bone but the rate of clearance from the bone is unknown.