Skelid (Tiludronate)
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Skelid (Tiludronate)

SKELID®
(tiludronate disodium)

DRUG DESCRIPTION

SKELID (tiludronate) is a bisphosphonate characterized by a (4-chlorophenylthio) group on the carbon atom of the basic P-C-P structure common to all bisphosphonates. Its generic name is tiludronate disodium. Tiludronate disodium is the hydrated hemihydrate form of the disodium salt of tiludronic acid. Its chemical name is [[(4-Chlorophenyl) thio]methylene]bis[phosphonic acid], disodium salt, and its structural formula is as follows:

SKELID®
  (tiludronate disodium)  Structural Formula Illustration

SKELID tablets for oral administration contain 240 mg tiludronate disodium, which is the molar equivalent of 200 mg tiludronic acid. SKELID (tiludronate) tablets also contain sodium lauryl sulfate, hydroxypropyl methylcellulose 2910, crospovidone, magnesium stearate, and lactose monohydrate.

What are the possible side effects of tiludronate (Skelid)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using tiludronate and call your doctor at once if you have any of these serious side effects:

  • painful or difficult swallowing;
  • severe heartburn, burning pain in your upper stomach, or coughing up blood;
  • severe joint, bone, or muscle pain;
  • jaw pain, numbness, or swelling;
  • severe diarrhea;
  • bone fracture; or
  • a red, blistering, peeling skin rash.

Less...

Read All Potential Side Effects and See Pictures of Skelid »

What are the precautions when taking tiludronate (Skelid)?

Before taking tiludronate, tell your doctor or pharmacist if you are allergic to it; or to other bisphosphonates (such as alendronate, etidronate); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, inability to sit upright or stand for at least 30 minutes, difficult/painful swallowing, esophagus problems (such as heartburn, narrowing of the esophagus), stomach/intestinal problems (such as ulcers), low level of calcium in the blood.

Infrequently, people taking this class of medication (bisphosphonates) have had serious jawbone problems...

Read All Potential Precautions of Skelid »

Last reviewed on RxList: 4/14/2010
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

SKELID (tiludronate) is indicated for treatment of Paget's disease of bone (osteitis deformans).

Treatment is indicated in patients with Paget's disease of bone (1) who have a level of serum alkaline phosphatase (SAP) at least twice the upper limit of normal, or (2) who are symptomatic, or (3) who are at risk for future complications of their disease.

DOSAGE AND ADMINISTRATION

A single 400-mg daily oral dose of SKELID (tiludronate) , taken with 6 to 8 ounces of plain water only, should be administered for a period of 3 months. Beverages other than plain water (including mineral water), food (see below), and some medications (see PRECAUTIONS: DRUG INTERACTIONS) are likely to reduce the absorption of SKELID (see CLINICAL PHARMACOLOGY, Pharmacokinetics).

Patients should not lie down for at least 30 minutes after taking this medication. In patients who cannot comply with dosing instructions due to mental or physical disability, therapy with SKELID (tiludronate) should be used under appropriate supervision (See WARNINGS).

SKELID (tiludronate) should not be taken within 2 hours of food.

Calcium or mineral supplements should be taken at least 2 hours before or two hours after SKELID (tiludronate) . Aluminum- or magnesium-containing antacids, if needed, should be taken at least two hours after taking SKELID (tiludronate) .

SKELID (tiludronate) should not be taken within 2 hours of indomethacin.

Following therapy, allow an interval of 3 months to assess response. Specific data regarding retreatment are limited, although results from uncontrolled studies indicate favorable biochemical improvement similar to initial SKELID (tiludronate) treatment.

HOW SUPPLIED

SKELID (tiludronate) is supplied as white to practically white, biconvex round tablets containing 240 mg tiludronate disodium, which is the molar equivalent of 200 mg tiludronic acid. SKELID (tiludronate) tablets are engraved with “S.W” on one side and “200” on the other side and packaged in foil strips in cartons of 56 tablets per carton (0024-1800-16).

Storage

SKELID (tiludronate) should be stored at 25° C (77° F); excursions permitted to 15° C to 30° C (59° F to 86° F) [see USP Controlled Room Temperature]. Tablets should not be removed from the foil strips until they are to be used.

sanofi-aventis U.S. LLC Bridgewater, NJ 08807, Country of origin: France. Revised March 2010

Last reviewed on RxList: 4/14/2010
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

The safety of SKELID (tiludronate) has been studied in more than 1100 patients, and the adverse experience profile is similar between controlled and uncontrolled clinical trials. Adverse events occurring in placebo-controlled trials of pagetic patients treated with SKELID (tiludronate) 400 mg/day are presented in the table below.

The most frequently occurring adverse events in patients who received SKELID (tiludronate) 400 mg/day were in the gastrointestinal body system: nausea (9.3%), diarrhea (9.3%), and dyspepsia (5.3%).

Adverse events associated with SKELID (tiludronate) usually have been mild, and generally have not required discontinuation of therapy. In two placebo-controlled trials, 1.3% of patients receiving 400 mg SKELID (tiludronate) and 5.4% of patients receiving placebo discontinued therapy due to any clinical adverse event.

Adverse Eventsa (%) Reportedb in > 2% of Pagetic Patients from Placebo-Controlled Studies

  SKELID (tiludronate)
400 mg/day
(n=75)
Placebo
(n=74)
BODY AS A WHOLE
  Pain 21.3 23.0
  Back Pain 8.0 8.1
  Accidental Injury 4.0 2.7
  Influenza-like Symptoms 4.0 5.4
  Chest Pain 2.7 0
  Peripheral Edema 2.7 1.4
CARDIOVASCULAR, GENERAL
  Dependent Edema 2.7 0
Central and Peripheral Nervous Systems
  Headache 6.7 12.2
  Dizziness 4.0 6.8
  Paresthesia 4.0 0
  Hyperparathyroidism 2.7 0
GASTROINTESTINAL
  Diarrhea 9.3 4.1
  Nausea 9.3 5.4
  Dyspepsia 5.3 8.1
  Vomiting 4.0 0
  Flatulence 2.7 0
  Tooth Disorder 2.7 1.4
Metabolic and Nutritional
  Vitamin D Deficiency 2.7 2.7
Musculoskeletal System
  Arthralgia 2.7 5.4
  Arthrosis 2.7 0
Resistance Mechanism
  Infection 2.7 0
Respiratory System
  Rhinitis 5.3 0
  Sinusitis 5.3 1.4
  Upper Respiratory Tract Infection 5.3 14.9
  Coughing 2.7 2.7
  Pharyngitis 2.7 1.4
Skin and Appendage
  Rash 2.7 1.4
  Skin Disorder 2.7 1.4
Vision
  Cataract 2.7 0
  Conjunctivitis 2.7 0
  Glaucoma 2.7 0
a Reported using WHO terminology
b All events reported, irrespective of causality

Other adverse events not listed in the table above but reported in ≥ 1% of pagetic patients treated with SKELID (tiludronate) in all clinical trials of at least one month duration, regardless of dose and causality assessment, are listed below. The adverse event terms within each body system are listed in the order of decreasing frequency occurring in the population.

Body as a Whole: Asthenia, syncope, fatigue

Cardiovascular: Hypertension

Central and Peripheral Nervous Systems: Vertigo, involuntary muscle contractions

Gastrointestinal: Abdominal pain, constipation, dry mouth, gastritis

Musculoskeletal: Fracture pathological

Psychiatric: Anorexia, somnolence, anxiety, nervousness, insomnia

Respiratory System: Bronchitis

Skin and Appendages: Pruritus, increased sweating

Urinary System: Urinary tract infection

Vascular (extracardiac): Flushing

Stevens-Johnson type syndrome has been observed rarely; the causality relationship of this to SKELID (tiludronate) has not been established.

Read the Skelid (tiludronate) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

The bioavailability of SKELID (tiludronate) is decreased 80% by calcium, when calcium and SKELID (tiludronate) are administered at the same time, and 60% by some aluminum- or magnesium-containing antacids, when administered 1 hour before SKELID (tiludronate) . Aspirin may decrease bioavailability of SKELID (tiludronate) by up to 50% when taken 2 hours after SKELID (tiludronate) . The bioavailability of SKELID (tiludronate) is increased 2-4 fold by indomethacin but is not significantly altered by coadministration of diclofenac. The pharmacokinetic parameters of digoxin are not significantly modified by SKELID (tiludronate) coadministration. In vitro studies show that tiludronate does not displace warfarin from its binding site on protein.

Last reviewed on RxList: 4/14/2010
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

SKELID (tiludronate) , like other bisphosphonates administered orally, may cause local irritation of the upper gastrointestinal mucosa. Because of these possible irritant effects and a potential for worsening of the underlying disease, caution should be used when SKELID (tiludronate) is given to patients with active upper gastrointestinal problems (such as known Barrett's esophagus, dysphagia, other esophageal diseases, gastritis, duodenitis, or ulcers).

Esophageal adverse experiences, such as esophagitis, esophageal ulcers and esophageal erosions, occasionally with bleeding and rarely followed by esophageal stricture or perforation, have been reported in patients receiving treatment with oral bisphosphonates. In some cases, these have been severe and required hospitalization. Physicians should therefore be alert to any signs or symptoms signaling a possible esophageal reaction and patients should be instructed to discontinue SKELID (tiludronate) and seek medical attention if they develop dysphagia, odynophagia, retrosternal pain or new or worsening heartburn.

The risk of severe esophageal adverse experiences appears to be greater in patients who lie down after taking oral bisphosphonates and/or who fail to swallow it with the recommended full glass (6-8oz) of water, and/or who continue to take oral bisphosphonates after developing symptoms suggestive of esophageal irritation. Therefore, it is very important that the full dosing instructions are provided to, and understood by, the patient (see DOSAGE AND ADMINISTRATION). In patients who cannot comply with dosing instructions due to mental or physical disability, therapy with SKELID (tiludronate) should be used under appropriate supervision.

There have been post-marketing reports of gastric and duodenal ulcers with oral bisphosphonate use, some severe and with complications, although no increased risk was observed in controlled clinical trials.

PRECAUTIONS

General

SKELID (tiludronate) is not recommended for patients with severe renal failure, for example, those with creatinine clearance < 30 mL/min (see CLINICAL PHARMACOLOGY, Renal Insufficiency).

Osteonecrosis, primarily in the jaw, has been reported in patients treated with bisphosphonates. Most cases have been in cancer patients undergoing dental procedures, but some have occurred in patients with postmenopausal osteoporosis or other diagnoses. Known risk factors for osteonecrosis include a diagnosis of cancer, concomitant therapies (e.g., chemotherapy, radiotherapy, corticosteroids), and co-morbid disorders (e.g., anemia, coagulopathy, infection, pre-existing dental disease). Most reported cases have been in patients treated with bisphosphonates intravenously but some have been in patients treated orally.

For patients who develop osteonecrosis of the jaw (ONJ) while on bisphosphonate therapy, dental surgery may exacerbate the condition. For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of ONJ. Clinical judgement of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment.

Musculoskeletal Pain

In post marketing experience, severe and occasionally incapaciting bone, joint, and/or muscle pain has been reported in patients taking bisphosphonates. However, such reports have been infrequent. This category of drugs includes SKELID (tiludronate) . The time to onset of symptoms varied from one day to several months after starting the drug. Most patients had relief of symptoms after stopping. A subset had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies have not yet been completed.

Tiludronate was not genotoxic in the following assays: an in vitro microbial mutagenesis assay with and without metabolic activation, a human lymphocyte assay, a yeast cell assay for forward mutation and mitotic crossing over, or the in vivo mouse micronucleus test.

Tiludronate had no effect on rat fertility (male or female) at exposures up to two times the 400 mg/day human dose, based on surface area, mg/m2 (75 mg/kg/day tiludronic acid dose).

Pregnancy

Pregnancy Category C

In a teratology study in rabbits dosed during days 6-18 of gestation at 42 mg/kg/day and 130 mg/kg/day (2 and 5 times the 400 mg/day human dose based on body surface area), there was dose-related scoliosis likely attributable to the pharmacologic properties of the drug.

Mice receiving 375 mg/kg/day tiludronic acid (7 times the 400 mg/day human dose based on body surface area, mg/m2) for days 6-15 of gestation showed slight maternal toxicity (decreased body weight gain), increased post-implantation loss, decreased number of fetuses/dam, and decreased fetus body weight. Uncommon malformations of the paw (shortened or missing digits, blood blisters between or in place of digits) were present in six fetuses at 375 mg/kg/day, all from the same litter.

Maternal toxicity (decreased body weight) was also observed in a teratology study in rats dosed during days 6-18 of gestation at 375 mg/kg/day tiludronic acid (10 times the 400 mg/day human dose based on body surface area, mg/m2). There were reduced percent implantations, increased postimplantation loss, and increased intra-uterine deaths in the rats. There were no teratogenic effects on fetuses.

Protracted parturition and maternal death, presumably due to hypocalcemia, occurred at 75 mg/kg/day tiludronic acid (two times the 400 mg/day human dose based on body surface area, mg/m2) when rats were treated from day 15 of gestation to day 25 postpartum.

There are no adequate and well-controlled studies in pregnant women. SKELID (tiludronate) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Bisphosphonates are incorporated into the bone matrix, from where they are gradually released over periods of weeks to years. The extent of bisphosphonate incorporation into adult bone, and hence, the amount available for release back into the systemic circulation, is directly related to the total dose and duration of bisphosphonate use. Although there are no data on fetal risk in humans, bisphosphonates do cause fetal harm in animals, and animal data suggest that uptake of bisphosphonates into fetal bone is greater than into maternal bone. Therefore, there is a theoretical risk of fetal harm (e.g., skeletal and other abnormalities) 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 this risk has not been established.

Nursing Mothers

It is not known whether tiludronate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when SKELID (tiludronate) is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of SKELID (tiludronate) in pediatric patients have not been established.

Last reviewed on RxList: 4/14/2010
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

Based on the known action of tiludronate, hypocalcemia is a potential consequence of SKELID (tiludronate) overdose. In one patient with hypercalcemia of malignancy, intravenous administration of high doses of SKELID (tiludronate) (800 mg/day total dose, 6 mg/kg/day for 2 days) was associated with acute renal failure and death.

No specific information is available on the treatment of overdose with SKELID (tiludronate) . Dialysis would not be beneficial. Standard medical practices may be used to manage renal insufficiency or hypocalcemia, if signs of these develop.

CONTRAINDICATIONS

SKELID (tiludronate) is contraindicated in individuals with known hypersensitivity to any component of this product.

Inability to stand or sit upright for at least 30 minutes.

Last reviewed on RxList: 4/14/2010
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

In vitro studies indicate that tiludronate disodium acts primarily on bone through a mechanism that involves inhibition of osteoclastic activity with a probable reduction in the enzymatic and transport processes that lead to resorption of the mineralized matrix.

Bone resorption occurs following recruitment, activation, and polarization of osteoclasts. Tiludronate disodium appears to inhibit osteoclasts through at least two mechanisms: disruption of the cytoskeletal ring structure, possibly by inhibition of protein-tyrosine-phosphatase, thus leading to detachment of osteoclasts from the bone surface and the inhibition of the osteoclastic proton pump.

Pharmacokinetics

Absorption

Relative to an intravenous (IV) reference dose, the mean oral bioavailability of tiludronate disodium in healthy male subjects was 6% after an oral dose equivalent to 400 mg tiludronic acid administered after an overnight fast and 4 hours before a standard breakfast. In single-dose studies, bioavailability was reduced by 90% when an oral dose equivalent to 400 mg

tiludronic acid 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. However, in clinical studies, efficacy was seen when SKELID (tiludronate) was dosed at least 2 hours before or after meals.

After administration of a single dose equivalent to 400 mg tiludronic acid to healthy male subjects, tiludronic acid was rapidly absorbed with peak plasma concentrations of approximately 3 mg/L occurring within 2 hours. In pagetic patients, after repeated administration of doses equivalent to 400 mg/day tiludronic acid (2 hours before or 2 hours after a meal) for durations of 12 days to 12 weeks, average plasma concentrations of tiludronic acid occurring between 1 and 2 hours after dosing ranged between 1 and 4.6 mg/L.

Distribution

Animal pharmacology studies in rats demonstrate that tiludronic acid is widely distributed to bone and soft tissues. Over a period of days, loss of drug occurs from most tissues with the exception of bone and cartilage. Tiludronate is then slowly released from bone with a half-life in rats of 30 days or longer depending on the status of bone turnover.

After oral administration of doses equivalent to 400 mg/day tiludronic acid to nonpagetic patients with osteoarthrosis, the steady state in bone was not reached after 30 days of dosing. At plasma concentrations between 1 and 10 mg/L, tiludronic acid was approximately 90% bound to human serum protein (mainly albumin).

Metabolism

In laboratory animals, tiludronic acid undergoes little if any metabolism. In vitro, tiludronic acid is not metabolized in human liver microsomes and hepatocytes.

Elimination

The principal route of elimination of tiludronic acid is in the urine. After IV administration to healthy volunteers, approximately 60% of the dose was excreted in the urine as tiludronic acid within 13 days. Renal clearance is dose independent and is approximately 10 mL/min in healthy subjects. In pagetic patients treated with doses equivalent to 400 mg/day tiludronic acid for 12 days, the mean apparent plasma elimination half-life was approximately 150 hours. The elimination rate from human bone is unknown.

Special Populations

Geriatric: No dosage adjustment in elderly patients is necessary. Plasma concentrations of tiludronic acid were higher in elderly pagetic patients ( ≥ 65 years of age); however, this difference was not clinically significant.

Pediatric: SKELID (tiludronate) pharmacokinetics have not been investigated in subjects under the age of 18 years.

Gender: There were no clinically significant differences in plasma concentrations after repeated administration of tiludronate disodium to male and female pagetic patients.

Race: Pharmacokinetic differences due to race have not been studied.

Renal Insufficiency: SKELID (tiludronate) is not recommended for patients with severe renal failure (creatinine clearance < 30 mL/min) due to lack of clinical experience. After a single oral dose equivalent to 400 mg tiludronic acid, subjects with creatinine clearance between 11 and 18 mL/min had Cmax values (approximately 3 mg/L) in the range of healthy volunteers. However, the plasma elimination half-life was approximately 205 hours, which is longer than that observed in pagetic patients after repeated doses (150 hours) and healthy subjects after single doses (50 hours). These values were obtained in a cross-study comparison between healthy volunteers and pagetic patients.

Hepatic Insufficiency: No dosage adjustment is needed. Since tiludronate undergoes little or no metabolism, no studies were conducted in subjects with hepatic insufficiency.

Drug-Drug Interactions

(See also PRECAUTIONS: DRUG INTERACTIONS) The bioavailability of SKELID (tiludronate) is decreased 80% by calcium, when calcium and SKELID (tiludronate) are administered at the same time, and 60% by some aluminum- or magnesium-containing antacids, when administered 1 hour before SKELID (tiludronate) . Aspirin may decrease bioavailability of SKELID (tiludronate) by up to 50% when taken 2 hours after SKELID (tiludronate) . The bioavailability of SKELID (tiludronate) is increased 2-4 fold by indomethacin and is not significantly altered by coadministration of diclofenac. The pharmacokinetic parameters of digoxin are not significantly modified by SKELID (tiludronate) coadministration. In vitro studies show that tiludronate disodium does not displace warfarin from its binding site on protein.

Summary of Pharmacokinetic Parameters in the Normal Population

Parameter Mean (SD)
Absolute bioavailability of two 200-mg tablets taken 4 hrs before standard breakfast 6% (2%)*
Time to peak plasma concentration (taken 4 hrs before first meal of day, n=151) 1.5 (0.9) hr
Maximum plasma concentration after a single 400-mg dose (taken 4 hrs before first meal of day, n=151) 2.66 (1.22) mg/L
Renal clearance after IV administration of 20-mg dose 0.54 (0.14) L/hr
*Bioavailability was reduced by 90% when this single oral dose of 400 mg was administered with, or 2 hours after, a standard breakfast.

Pharmacodynamics

Paget's disease of bone is a chronic, focal skeletal disorder characterized by greatly increased and disorderly bone remodeling. Excessive osteoclastic bone resorption is followed by osteoblastic new bone formation, leading to the replacement of the normal bone architecture by disorganized, enlarged, and weakened bone structure.

Clinical manifestations of Paget's disease range from no symptoms to severe bone pain, bone deformity, pathological fractures, and neurological and other complications. Serum alkaline phosphatase, the most frequently used biochemical index of disease activity, provides an objective measure of disease severity and response to therapy.

In pagetic patients treated with SKELID (tiludronate) 400 mg/day for 3 months, changes in urinary hydroxyproline, a biochemical marker of bone resorption, and in serum alkaline phosphatase, a marker of bone formation, indicate a reduction toward normal in the rate of bone turnover. In addition, reduced numbers of osteoclasts by histomorphometric analysis and radiological improvement of lytic lesions indicate that SKELID (tiludronate) can suppress the pagetic disease process.

Clinical Studies

The efficacy of SKELID (tiludronate) 400 mg/day treatment was demonstrated in two randomized, double-blind, placebo-controlled multicenter studies and one positive-controlled study. All three studies included male and female patients with Paget's disease of the bone (radiograph examination and level of serum alkaline phosphatase [SAP] at least twice the upper normal limit). In one placebo-controlled study, conducted in North America, patients were randomly assigned to receive a daily dose of placebo or 200 or 400 mg/day SKELID (tiludronate) for 3 months followed by an additional 12 weeks without treatment. A second placebo-controlled study of similar design was conducted in the UK.

A positive-controlled study was conducted in Europe with treatment groups of 400 mg/day SKELID (tiludronate) for 3 months with a 3-month treatment-free follow-up, 400 mg/day SKELID (tiludronate) for 6 months, and 400 mg/day etidronate for 6 months. In all of these studies, the efficacy of SKELID (tiludronate) was primarily assessed by SAP activity after 3 and 6 months.

Figure 1

Suppression of SAP levels - Illustration

In the placebo-controlled trials, suppression of SAP levels was statistically significantly greater with 400 mg/day SKELID (tiludronate) both at the end of treatment (3 months) and on follow-up (6 months) than with placebo (See Figure 1). The proportion of patients demonstrating at least a 50% reduction in SAP at 3 months with 400 mg/day SKELID (tiludronate) was 61% in the North American study and 52% in the UK study.

Figure 2

SKELID®
  (tiludronate disodium) Figure 2  Illustration

In the positive-controlled trial, six months after the start of dosing, the decrease in SAP levels in patients who ceased dosing after a 3-month course of SKELID (tiludronate) was significantly greater than with 6 months of etidronate 400 mg/day, and was equivalent to levels in patients who completed a 6-month course of SKELID (tiludronate) (See Figure 2).

Treatment effects of SKELID (tiludronate) were similar, regardless of pagetic patients' baseline SAP level, gender or age in the population studied.

Histomorphometry of the bone was studied in 19 pagetic and 29 nonpagetic patients. Bone biopsy results in nonpagetic bone confirmed that SKELID (tiludronate) did not impair bone remodeling or induce a significant decline in bone turnover. Results obtained in pagetic and nonpagetic bone indicated no evidence of osteomalacia or accumulation of unmineralized osteoid, and there was no reduction in the mineralization rate.

Last reviewed on RxList: 4/14/2010
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Patients receiving SKELID (tiludronate) should be instructed to:

  1. Take SKELID (tiludronate) with 6 to 8 ounces of plain water.
  2. Not lie down for at least 30 minutes after taking this medication.
  3. SKELID (tiludronate) should not be taken within 2 hours of food.
  4. Maintain adequate vitamin D and calcium intake.
  5. Calcium supplements, aspirin, and indomethacin should not be taken within 2 hours before or 2 hours after SKELID (tiludronate) .
  6. Aluminum- or magnesium-containing antacids, if needed, should be taken at least 2 hours after taking SKELID (tiludronate) .

Last reviewed on RxList: 4/14/2010
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

Patients receiving SKELID (tiludronate) should be instructed to:

  1. Take SKELID (tiludronate) with 6 to 8 ounces of plain water.
  2. Not lie down for at least 30 minutes after taking this medication.
  3. SKELID (tiludronate) should not be taken within 2 hours of food.
  4. Maintain adequate vitamin D and calcium intake.
  5. Calcium supplements, aspirin, and indomethacin should not be taken within 2 hours before or 2 hours after SKELID (tiludronate) .
  6. Aluminum- or magnesium-containing antacids, if needed, should be taken at least 2 hours after taking SKELID (tiludronate) .

Last reviewed on RxList: 4/14/2010
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Skelid Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

TILUDRONATE - ORAL

(till-EW-dro-nate)

COMMON BRAND NAME(S): Skelid

USES: Tiludronate is used to treat a certain type of bone disease called Paget's disease. This disease weakens and deforms bones. Tiludronate works by slowing bone loss, helping to keep your bones strong and less likely to break. It also helps reduce bone pain from this disease. This medication belongs to a class of drugs called bisphosphonates.

HOW TO USE: Follow these instructions very closely to make sure you absorb as much of the drug as possible and reduce the risk of injury to your esophagus. Consult your doctor or pharmacist if you have any questions.

Take this medication by mouth without food, usually once a day or as directed by your doctor. Take it on an empty stomach at least 2 hours before or 2 hours after a meal.

Take tiludronate with a full glass of plain water (6 to 8 ounces, 180 to 240 milliliters). Do not take it with any other beverage. After taking tiludronate, stay fully upright (sitting, standing, or walking) and do not lie down for at least 30 minutes.

Do not take tiludronate at the same time as food or other medications because they may affect its absorption. Take this medication 2 hours before or 2 hours after taking any products that contain aluminum, calcium, iron, magnesium, or zinc. Some examples include certain forms of didanosine (chewable/dispersible buffered tablets or pediatric oral solution), quinapril, vitamins/minerals, dairy products (such as milk, yogurt), and calcium-enriched juice.

If you take antacids that contain aluminum or magnesium, take them at least 2 hours after taking tiludronate.

If you take aspirin or indomethacin, take the dose 2 hours before or 2 hours after your tiludronate dose.

Take this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day, usually for 3 months or as directed by your doctor.

Disclaimer

Skelid Consumer (continued)

SIDE EFFECTS: Nausea or diarrhea may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: new or worsening bone/joint/muscle pain, new or unusual hip/thigh/groin pain, jaw pain, eye/vision problems.

This medication may infrequently cause irritation and ulcers in your stomach or esophagus. Seek immediate medical attention if any of these serious side effects occur: new/severe/worsening heartburn, chest pain, difficult/painful swallowing, stomach/abdominal pain, black/tarry stools, vomit that looks like coffee grounds.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Skelid (tiludronate) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking tiludronate, tell your doctor or pharmacist if you are allergic to it; or to other bisphosphonates (such as alendronate, etidronate); or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, inability to sit upright or stand for at least 30 minutes, difficult/painful swallowing, esophagus problems (such as heartburn, narrowing of the esophagus), stomach/intestinal problems (such as ulcers), low level of calcium in the blood.

Infrequently, people taking this class of medication (bisphosphonates) have had serious jawbone problems (osteonecrosis). Lack of proper dental hygiene, poorly fitting dentures, or certain dental procedures (such as tooth extraction, dental surgery) may increase your risk. Medical conditions (such as gum disease/infection, cancer, anemia) might also increase the risk. If you develop jaw pain, tell your doctor and dentist immediately.

Before having any surgery (especially dental procedures), tell your doctor and dentist about this medication and all other products you use (including prescription drugs, nonprescription drugs, and herbal products). Your doctor or dentist may tell you to stop taking tiludronate before your surgery. Ask for specific instructions about stopping or starting this medication.

Caution is advised if you are pregnant or planning to become pregnant in the future. This medication may stay in your body for many years. Its effects on an unborn baby are not known. Discuss the risks and benefits with your doctor before starting treatment with this medication.

It is not known if this medication passes into breast milk, and the effect on a nursing infant is unknown. Consult your doctor before breast-feeding.

Disclaimer

Skelid Consumer (continued)

DRUG INTERACTIONS: See also the How to Use section.

Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Check the labels on all your medicines because they may contain aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs such as ibuprofen, naproxen) that could also cause stomach irritation/ulcers. Ask your pharmacist about using these products safely. If your doctor has prescribed low doses of aspirin to prevent heart attack or stroke (usually at dosages of 81-325 milligrams a day), you should continue to take the aspirin. Consult your doctor or pharmacist for more details.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: muscle spasms, mental/mood changes.

NOTES: Do not share this medication with others.

Eat well-balanced meals that contain adequate calcium and vitamin D. You may also need to take calcium and vitamin D supplements. Consult your doctor for specific advice.

Laboratory and/or medical tests (such as X-rays, height, blood mineral levels) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember, following the dose-timing instructions in the How to Use section. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Do not remove the tablets from the packaging until you are ready to use them. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised December 2011. Copyright(c) 2011 First Databank, Inc.

Skelid Patient Information Including Side Effects

Brand Names: Skelid

Generic Name: tiludronate (Pronunciation: til UD ro nayt)

What is tiludronate (Skelid)?

Tiludronate is in the group of medicines called bisphosphonates (bis FOS fo nayts). It alters the cycle of bone formation and breakdown in the body.

Tiludronate is used to treat Paget's disease of bone.

Tiludronate may also be used for purposes not listed in this medication guide.

What are the possible side effects of tiludronate (Skelid)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Stop using tiludronate and call your doctor at once if you have any of these serious side effects:

  • painful or difficult swallowing;
  • severe heartburn, burning pain in your upper stomach, or coughing up blood;
  • severe joint, bone, or muscle pain;
  • jaw pain, numbness, or swelling;
  • severe diarrhea;
  • bone fracture; or
  • a red, blistering, peeling skin rash.

Less serious side effects may include:

  • nausea, vomiting, upset stomach;
  • mild diarrhea; or
  • runny or stuffy nose.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Skelid (tiludronate) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about tiludronate (Skelid)?

Take tiludronate with a full glass (6 to 8 ounces) of water. Use only plain water (not mineral water) when taking a tiludronate tablet.

For at least the first 2 hours after taking tiludronate, do not eat or drink anything other than plain water, and do not take any other medicines including vitamins or mineral supplements.

Especially avoid drinking milk or eating dairy products within 2 hours after taking tiludronate. Also avoid taking supplements that contain calcium, magnesium, iron, or aluminum (such as in multivitamins with iron, and in many types of antacids).

Some people using medicines similar to tiludronate have developed bone loss in the jaw, also called osteonecrosis of the jaw. Symptoms may include jaw pain, swelling, numbness, loose teeth, gum infection, or slow healing after injury or surgery involving the gums. You may be more likely to develop osteonecrosis of the jaw if you have cancer or have been treated with chemotherapy, radiation, or steroids. Other conditions associated with osteonecrosis of the jaw include blood clotting disorders, anemia (low red blood cells), and a pre-existing dental problem.

If you need to have any dental work (especially surgery), tell the dentist ahead of time that you are using tiludronate. You may need to stop using the medicine for a short time.

Talk with your doctor about the risks and benefits of using this medication.

Side Effects Centers

Skelid Patient Information including How Should I Take

What should I discuss with my healthcare provider before taking tiludronate (Skelid)?

Do not take a tiludronate tablet if you cannot sit upright or stand for at least 30 minutes. Tiludronate can cause serious problems in the stomach or esophagus (the tube that connects your mouth and stomach). You will need to stay upright for at least 30 minutes after taking this medication.

To make sure you can safely take tiludronate, tell your doctor if you have any of these other conditions:

  • diarrhea;
  • a bone fracture;
  • trouble swallowing;
  • a stomach or esophageal ulcer or disease; or
  • kidney disease.

Some people using medicines similar to tiludronate have developed bone loss in the jaw, also called osteonecrosis of the jaw. Symptoms may include jaw pain, swelling, numbness, loose teeth, gum infection, or slow healing after injury or surgery involving the gums.

You may be more likely to develop osteonecrosis of the jaw if you have cancer or have been treated with chemotherapy, radiation, or steroids. Other conditions associated with osteonecrosis of the jaw include blood clotting disorders, anemia (low red blood cells), and a pre-existing dental problem.

Talk with your doctor about the risks and benefits of using this medication.

FDA pregnancy category C. It is not known whether tiludronate will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication..

It is not known whether tiludronate passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take tiludronate (Skelid)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Do not crush, chew, or suck the pill. Swallow it whole.

Take each tiludronate tablet with a full glass (6 to 8 ounces) of water. Use only plain water (not mineral water) when taking a tiludronate tablet.

For at least the first 2 hours after taking tiludronate, do not eat or drink anything other than plain water, and do not take any other medicines including vitamins or mineral supplements.

Use tiludronate regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

If you need to have any dental work (especially surgery), tell the dentist ahead of time that you are using tiludronate. You may need to stop using the medicine for a short time.

Your doctor will need to check your progress on a regular basis. Do not miss any scheduled appointments.

Tiludronate is only part of a complete program of treatment that may also include taking calcium and vitamin supplements. Follow your diet, medication, and exercise routines very closely.

Store at room temperature away from moisture and heat.

Side Effects Centers

Skelid Patient Information including If I Miss a Dose

What happens if I miss a dose (Skelid)?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Skelid)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include vomiting, numbness or tingly feeling around your mouth, fast or slow heart rate, muscle tightness or contraction, overactive reflexes.

What should I avoid while taking tiludronate (Skelid)?

Avoid drinking milk or eating dairy products within 2 hours after taking tiludronate. Also avoid taking supplements that contain calcium, magnesium, iron, or aluminum (such as in multivitamins with iron, and in many types of antacids).

What other drugs will affect tiludronate (Skelid)?

There may be other drugs that can interact with tiludronate. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about tiludronate.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 3.01. Revision date: 7/25/2011.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

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