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Treatment of Paget's disease of the bone in patients who have a level of serum alkaline phosphatase (SAP) at least twice the upper limit of normal, or who are symptomatic, or who are at risk for future complications of their disease
Teratogenic and nonteratogenic embryo/fetal effects have been reported in animal studies. There are no adequate and well-controlled studies in pregnant women. Bisphosphonates are incorporated into the bone matrix and gradually released over time. Theoretically, there may be a risk of fetal harm when pregnancy follows the completion of therapy. Based on limited case reports with pamidronate, serum calcium levels in the newborn may be altered if administered during pregnancy.
Excretion in breast milk unknown/use caution
Hypersensitivity to bisphosphonates or any component of the formulation
Not recommended in patients with severe renal impairment (Clcr<30 mL/minute). Use with caution in patients with active upper GI problems (eg, dysphagia, symptomatic esophageal diseases, gastritis, duodenitis, ulcers).
The following events occurred >2% and at a frequency > placebo:
1% to 10%:
Cardiovascular: Chest pain (3%), edema (3%)
Central nervous system: Dizziness (4%), paresthesia (4%)
Dermatologic: Rash (3%), skin disorder (3%)
Gastrointestinal: Nausea (9%), diarrhea (9%), heartburn (5%), vomiting (4%), flatulence (3%)
Neuromuscular & skeletal: Arthrosis (3%)
Ocular: Cataract (3%), conjunctivitis (3%), glaucoma (3%)
Respiratory: Rhinitis (5%), sinusitis (5%), cough (3%), pharyngitis (3%)
<1% (Limited to important or life-threatening): Stevens-Johnson syndrome
Postmarketing and/or case reports: Osteonecrosis
Hypocalcemia is a potential consequence of overdose. Treatment is supportive.
Calcium supplements, antacids interfere with the bioavailability (decreased 60%) when administered 1 hour before tiludronate
Aspirin decreases the bioavailability of tiludronate by up to 50% when taken 2 hours after tiludronate
Increased effect/toxicity: Indomethacin increases the bioavailability of tiludronate two- to fourfold
Food: In single-dose studies, the bioavailability of tiludronate was reduced by 90% when an oral dose was administered with, or 2 hours after, a standard breakfast compared to the same dose administered after an overnight fast and 4 hours before a standard breakfast.
Do not remove tablets from the foil strips until they are to be used
Inhibition of normal and abnormal bone resorption. Inhibits osteoclasts through at least two mechanisms: disruption of the cytoskeletal ring structure, possibly by inhibition of protein-tyrosine-phosphatase, thus leading to the detachment of osteoclasts from the bone surface area and the inhibition of the osteoclast proton pump.
Onset of action: Delayed, may require several weeks
Distribution: Widely to bone and soft tissue
Protein binding: 90%, primarily to albumin
Metabolism: Little, if any
Bioavailability: 6%; reduced by food
Half-life elimination: Healthy volunteers: 50 hours; Pagetic patients: 150 hours
Time to peak, plasma: ~2 hours
Excretion: Urine (60% as unchanged drug) within 13 days
Tiludronate should be taken with 6-8 oz of plain water and not taken within 2 hours of food
Adults: Oral: 400 mg (2 tablets of tiludronic acid) daily for a period of 3 months; allow an interval of 3 months to assess response
Dosing adjustment in renal impairment: Clcr<30 mL/minute: Not recommended
Dosing adjustment in hepatic impairment: Adjustment is not necessary
Administer as a single oral dose, take with 6-8 oz of plain water. Beverages other than plain water (including mineral water), food, and some medications (see Drug Interactions) are likely to reduce the absorption of tiludronate. Do not take within 2 hours of food. Take calcium or mineral supplements at least 2 hours before or after tiludronate. Take aluminum- or magnesium-containing antacids at least 2 hours after taking tiludronate. Do not take tiludronate within 2 hours of indomethacin.
Do not take within 2 hours of food.
Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Do not remove medication from foil strip until ready to be used. Take as directed, on an empty stomach with a full glass of water. Do not take within 2 hours of food, aspirin, indomethacin, or calcium-, magnesium-, or aluminum-containing medications. Stay in sitting or standing position for 30 minutes following administration. Consult prescriber to determine possibility of lifestyle changes (eg, decreased smoking, decreased alcohol intake, dietary supplements of calcium, or increased dietary vitamin D). May cause mild skin rash; or abdominal pain, diarrhea, or constipation (report if persistent). Report unresolved muscle or bone pain or leg cramps; acute abdominal pain; chest pain, palpitations, or swollen extremities; disturbed vision or excessively dry eyes; ringing in the ears; persistent rash or skin disorder; or unusual weakness or increased perspiration. Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.Pregnancy/breast-feeding precautions:
No significant effects or complications reported
No information available to require special precautions
May cause dizziness, anxiety, or nervousness
Tablet, tiludronic acid: 200 mg [equivalent to 240 mg tiludronate disodium]
French AE, Kaplan N, Lishner M, et al, "Taking Bisphosphonates During Pregnancy,"Can Fam Physician, 2003, 49:1281-2.
Ruggiero SL, Mehrotra B, Rosenberg TJ, et al, "Osteonecrosis of the Jaws Associated With the Use of Bisphosphonates: A Review of 63 Cases,"J Oral Maxillofac Surg, 2004, 62(5):527-34.