Usual Adult Dose for Paget's Disease

Initial Treatment Regimens:

• 5 to 10 mg/kg/day orally once a day, not to exceed 6 months, or
• 11 to 20 mg/kg/day orally once a day, not to exceed 3 months

• Doses above 10 mg/kg/day should be reserved for when lower doses are ineffective, or if there is an overriding need to suppress rapid bone turnover (especially when irreversible neurologic damage is possible), or to reduce elevated cardiac output.
• Doses above 20 mg/kg/day are not recommended.

• Retreatment should be initiated only after: A drug-free period of at least 90 days; and when there is biochemical, symptomatic, or other evidence of active disease process.
• Patients should be monitored every 3 to 6 months, although some patients may go drug free for extended periods.
• Retreatment regimens are the same as for initial treatment. For most patients the original dose will be adequate. If not, consider increasing the dose within the recommended guidelines.

• Response to therapy may be of slow onset and may continue for months after therapy with this drug is discontinued. In some patients, the disease process will be suppressed for at least one year, or more, following cessation of therapy.
• Dosage should not be increased prematurely nor should treatment be resumed before there is clear evidence of reactivation of the disease process.
• Patients should adhere to the recommended dose regimen to avoid over- treatment with this drug.

• Treatment of symptomatic Paget's disease of bone
• The effects of this drug in patients with asymptomatic Paget's disease have not been studied; however, treatment may be warranted if extensive involvement threatens irreversible neurologic damage, major joints, or major weight-bearing bones.

Usual Adult Dose for Heterotopic Ossification - Spinal Cord Injury

Total Hip Replacement:

• 20 mg/kg/day orally once a day, for 1 month before and 3 months after surgery (4 months total).

• 20 mg/kg/day orally once a day, for 2 weeks followed by 10 mg/kg/day for 10 weeks (12 weeks total).

• Therapy should begin as soon as medically feasible following the injury, preferably prior to evidence of heterotopic ossification.
• Retreatment has not been studied.
• In total hip replacement patients, this drug does not promote loosening of the prosthesis or impede trochanteric reattachment.
• In spinal cord injury patients, this drug does not inhibit fracture healing or stabilization of the spine.

Usual Adult Dose for Heterotopic Ossification - Total Hip Arthroplasty

Total Hip Replacement:

• 20 mg/kg/day orally once a day, for 1 month before and 3 months after surgery (4 months total).

• 20 mg/kg/day orally once a day, for 2 weeks followed by 10 mg/kg/day for 10 weeks (12 weeks total).

• Therapy should begin as soon as medically feasible following the injury, preferably prior to evidence of heterotopic ossification.
• Retreatment has not been studied.
• In total hip replacement patients, this drug does not promote loosening of the prosthesis or impede trochanteric reattachment.
• In spinal cord injury patients, this drug does not inhibit fracture healing or stabilization of the spine.

Renal Dose Adjustments

Dose adjustment may be required; however, no specific guidelines have been suggested.

Dosage should be reduced when reductions in glomerular filtration rates are present; close monitoring is recommended.

Liver Dose Adjustments

Caution recommended.

Dose Adjustments

Dose selection for geriatric patients should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy. Caution is recommended.

Precautions

Safety and efficacy have not been established in patients younger than 18 years.

Pediatric patients have been treated at doses recommended for adults, to prevent heterotopic ossifications or soft tissue calcifications; however, a rachitic syndrome has been reported infrequently at doses of 10 mg/kg/day and more for prolonged periods approaching or exceeding a year.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Administer as a single oral dose; however, if gastrointestinal discomfort occurs, the dose may be divided.
• Take with 6 to 8 ounces of water; patients should not lie down after taking the medication.
• To maximize absorption, avoid taking the following food (especially food high in calcium, such as milk or milk products), vitamins with mineral supplements, or antacids within 2 hours of dosing.

• This drug is indicated for the treatment of symptomatic Paget's disease of bone and in the prevention and treatment of heterotopic ossification following total hip replacement or due to spinal cord injury.
• It is not approved for the treatment of osteoporosis.

• Report any thigh, hip, or groin pain; these symptoms should be evaluated for an incomplete femur fracture.
• Failure to follow administration instructions for this drug may increase the risk of esophageal adverse reactions.
• Discontinue this drug and seek medical attention if dysphagia, odynophagia, retrosternal pain or new or worsening heartburn develop.