tiludronate

Action and Spectrum

Actions and Spectrum:

tiludronate is a bisphosphonate medication that is primarily used in the treatment of osteoporosis and other bone disorders. Its mechanism of action involves inhibiting the activity of osteoclasts, which are the cells that break down bone tissue.

tiludronate binds strongly to hydroxyapatite crystals, the main component of bone tissue, and accumulates in the bone matrix. This binding inhibits the activity of osteoclasts by preventing them from attaching to the bone surface and resorbing it. This results in a decrease in bone turnover, which helps to maintain or increase bone density.

tiludronate has a broad spectrum of activity and effectively treats various bone disorders. It has been shown to increase bone mineral density and reduce the risk of fractures in patients with osteoporosis, Paget’s disease of bone, and bone metastases from certain types of cancer. tiludronate has also been used to treat hypercalcemia (high calcium levels in the blood) associated with malignancy.

Drug Interaction

Adverse Reaction

Frequency defined

1-10%

Edema (2.7%)

Flushing

Hypertension

Dizziness (4%)

Insomnia

Chest pain

Frequency not defined

Musculoskeletal pain

Dyspepsia

Headache

Rhinitis

URI

Back pain

Diarrhea

Flushing

Nausea

Sinusitis

Black Box Warning

None

Contraindication / Caution

Contraindications/caution:

Contraindications:

• Hypersensitivity or allergy to bisphosphonates or any of the components of the formulation.
• Severe kidney disease or impairment.
• Inability to stand or sit upright for at least 30 minutes after taking the medication, as this is necessary to reduce the risk of esophageal irritation and ulceration.
• Calcium or vitamin D deficiency, as these nutrients are necessary for proper bone metabolism, and tiludronate may exacerbate their deficiency.
• Pregnancy or breastfeeding, as the safety of tiludronate in these situations, has not been established.
• Esophageal abnormalities or disorders, such as strictures or achalasia, may increase the risk of esophageal irritation and ulceration.
• Severe gastrointestinal disorders, such as inflammatory bowel disease, may interfere with the absorption and effectiveness of tiludronate.

Caution:

• Renal impairment: tiludronate is excreted primarily by the kidneys, so it should be used cautiously in patients with mild to moderate renal impairment. Dose adjustments may be necessary for these patients.
• Gastrointestinal disorders: tiludronate may cause gastrointestinal side effects such as nausea, vomiting, and abdominal pain. It should be used cautiously in patients with a history of gastrointestinal disorders, such as peptic ulcers or gastroesophageal reflux disease.
• Musculoskeletal pain: Bisphosphonates, including tiludronate, have been associated with musculoskeletal pain and rare cases of severe bone, joint, and muscle pain. If these symptoms occur, the patient should consult their healthcare provider.
• Osteonecrosis of the jaw: Bisphosphonates have been associated with rare cases of osteonecrosis of the jaw (ONJ), a condition in which the bone tissue in the jaw fails to heal after minor trauma, such as dental procedures. Patients should avoid invasive dental procedures while taking bisphosphonates and inform their dentist that they are taking the medication.

Atypical fractures: Bisphosphonates have been associated with rare atypical femur fractures, which may occur with minimal or no trauma. Patients should report any thigh or groin pain while taking bisphosphonates, as this may be a sign of an atypical fracture.

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available

Lactation: Excretion of the drug in human breast milk is unknown

Pregnancy category:

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:

tiludronate is a bisphosphonate medication that acts primarily on bone tissue. It is a pyridinyl bisphosphonate, which means it contains a pyridine ring in its structure.

tiludronate works by binding to hydroxyapatite crystals in the bone matrix, inhibiting osteoclast activity. Osteoclasts are the cells responsible for bone resorption or the breakdown of bone tissue. By inhibiting osteoclasts’ activity, tiludronate helps reduce bone turnover and maintain or increase bone density.

Pharmacodynamics:

The pharmacodynamics of tiludronate primarily involve its actions on bone tissue. Tiludronate is a potent inhibitor of bone resorption, which is the process by which bone tissue is broken down, and its minerals are released into the bloodstream. The inhibition of bone resorption is achieved by binding tiludronate to hydroxyapatite crystals in the bone matrix, which inhibits the activity of osteoclasts, the cells responsible for bone resorption.

tiludronate reduces the rate of bone turnover, which results in an increase in bone density and a decrease in the risk of fractures. It also reduces calcium levels in the blood, which is beneficial in treating hypercalcemia or malignancy.

The pharmacodynamic effects of tiludronate are primarily observed in bone tissue. The medication has little or no effect on other tissues or organs in the body.

Pharmacokinetics:

Absorption

tiludronate is not well absorbed orally, with only about 1-2% of the dose being absorbed from the gastrointestinal tract. Therefore, taking tiludronate on an empty stomach with a full glass of water is recommended to enhance its absorption.

Distribution

After absorption, tiludronate is rapidly taken up by bone tissue, where it binds to hydroxyapatite crystals. The medication has a large volume of distribution, indicating that it is widely distributed throughout the body.

Metabolism

tiludronate is not metabolized in the body and is eliminated unchanged primarily by the kidneys. Therefore, tiludronate does not undergo hepatic metabolism, and there is no requirement for dose adjustment in patients with hepatic impairment.

Elimination and Excretion

tiludronate is primarily excreted in the urine, with around 90% of the dose being eliminated by the kidneys within 72 hours. Clearance of tiludronate is reduced in patients with renal impairment, and dosage adjustments are required in these patients.

Adminstartion

Administration:

Oral administration: The oral formulation of tiludronate is taken once daily on an empty stomach with a full glass of water. Taking the medication at least 2 hours before or after other medications, food, or beverages (except for water) is recommended. The tablet should be swallowed whole, not crushed, chewed, or dissolved.

Intravenous administration: A healthcare professional administers the intravenous formulation of tiludronate. It is typically given once every three months as a 30-minute infusion. The infusion should be administered slowly and not mixed with other medications.

Patient Information Leaflet

Patient information leaflet

Generic Name: tiludronate

Why do we use tiludronate?

tiludronate is primarily used to treat and prevent osteoporosis, a condition characterized by a loss of bone density and an increased risk of fractures. The medication works by inhibiting bone resorption, which results in an increase in bone density and a decrease in the risk of fractures.

tiludronate may also be used to treat hypercalcemia of malignancy, a condition in which an abnormally high calcium level is in the blood due to cancer.

Additionally, tiludronate has been studied for its potential use in treating other bone-related disorders, such as Paget’s disease of bone, osteogenesis imperfecta, and bone metastases.