Difosfonal

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

Difosfonal is a first generation bisphosphonate similar to etidronic acid and tiludronic acid. These drugs were developed to mimic the action of pyrophosphate, a regulator of calcification and decalcification. clodronate’s use has decreased over the years in favor of the third generation, nitrogen containing bisphosphonate zoledronic acid, ibandronic acid, minodronic acid, and risedronic acid.

Difosfonal is not FDA approved, but is approved in Canada.

Difosfonal is a first generation bisphosphonate that inhibits osteoclast mediated bone resorption. It has a wide therapeutic index as a large overdose is required for significant toxicity and a long duration of action due to the slow release from bone. Patients should be counselled regarding the risk of hypocalcemia, hypovolemia, renal insufficiency, transient hyperphosphatemia, and transient hyperparathyroidism.

Difosfonal
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	Difosfonal
Generic	Clodronic acid
Clodronic acid Other Names	Acide clodronique, Acido clodronico, Acidum clodronicum, Clodronate, Clodronic acid, Clodronsaeure, Clodronsäure, Dichloromethylidene diphosphonate
Type
Formula	CH₄Cl₂O₆P₂
Weight	Average: 244.892 Monoisotopic: 243.886016298
Protein binding	Clodronic acid is 36% protein bound in plasma.
Groups	Approved, Investigational, Vet approved
Therapeutic Class
Manufacturer
Available Country	Italy
Last Updated:	September 19, 2023 at 7:00 am

Uses

Difosfonal is a bisphosphonate used to treat osteoporosis in postmenopausal women, hypercalcemia of malignancy, and osteolysis.

Difosfonal is indicated as an adjunct in the management of osteolysis from bone metastases of malignant tumors and for management of hypercalcemia of malignancy.

Difosfonal is also used to associated treatment for these conditions: Hypercalcemia of Malignancy, Osteolytic Bone metastases

How Difosfonal 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. Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption.

First generation bisphosphonates closely mimic the structure of pyrophosphate, which can be incorporated into ATP anologues that cannot be hydrolyzed, disrupting all ATP mediated actions of osteoclasts.

Toxicity

Patients experiencing an overdose may present with hypocalcemia, while severe overdoses can present with kidney failure, liver damage, and unconsciousness. Overdose can be managed through symptomatic and supportive care, including monitoring and administration of electrolytes including calcium. Gastric lavage may remove unabsorbed drug in the gastrointestinal tract.

Food Interaction

Take on an empty stomach. Co-administration with food may decrease absorption.

Elimination Route

Oral clodronic acid has a bioavailability of 1-2%. A 200mg intravenous dose reaches a C_max of 16.1mg/L with an AUC of 44.2mg*h/L. A 200mg intramuscular dose reaches a C_max of 12.8mg/L with an AUC of 47.5mg*h/L. Further pharmacokinetic data for clodronic acid are not readily available.