Etidronate

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

Etidronate is used to treat Paget's disease, and to treat conditions of irregular bone growth due to hip fracture or spinal cord injury.

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

You should not take this medicine if you have a condition called osteomalacia (softening of the bones), or a problem with the movement of muscles in your esophagus.

You should not take this medicine if you have a condition called osteomalacia (softening of the bones), or a problem with the movement of muscles in your esophagus.

To make sure etidronate is safe for you, tell your doctor if you have:

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

In rare cases, this medicine may cause bone loss (osteonecrosis) in the jaw. Symptoms include jaw pain or numbness, red or swollen gums, loose teeth, or slow healing after dental work. The longer you use etidronate, the more likely you are to develop this condition.

Osteonecrosis of the jaw may be more likely if you have cancer or received chemotherapy, radiation, or steroids. Other risk factors 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.

It is not known whether etidronate 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 etidronate passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

• Store at room temperature.
• Protect from heat.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Etidronate Disodium Tablets, USP are available containing 200 mg or 400 mg of Etidronate disodium, USP.

The 200 mg tablets are white, rectangular-shaped tablets with ED 200 on one side and G on the other side. They are available as follows:

NDC 0378-3286-91
bottles of 60

The 400 mg tablets are white, capsule-shaped tablets with ED 400 on one side and G on the other side. They are available as follows:

NDC 0378-3288-91
bottles of 60

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Avoid excessive heat (over 104°F or 40°C).

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Manufactured by:
ALPHAPHARM PTY LTD
15 Garnet Street
Carole Park QLD 4300
Australia

ALP:ETDN:R8
Revised: 3/2017

PRINCIPAL DISPLAY PANEL - 200 mg

NDC 0378-3286-91

Etidronate
Disodium
Tablets, USP
200 mg

Rx only     60 Tablets

Each tablet contains:
Etidronate disodium, USP   200 mg

Dispense in a tight, light-resistant
container as defined in the USP
using a child-resistant closure.

Keep container tightly closed.

Keep this and all medication
out of the reach of children.

Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room
Temperature.]

Avoid excessive heat (over 104°F
or 40°C).

Usual Dosage: See accompanying
prescribing information.

Manufactured for:
Mylan Pharmaceuticals Inc.
Morgantown, WV 26505 U.S.A.

Made in Australia

3290/0

RM3286D4

• Bisphosphonate Derivative

No dosage adjustment provided in manufacturer's labeling.

Concerns related to adverse effects:

• Bone/joint/muscle pain: Infrequently, severe (and occasionally debilitating) bone, joint, and/or muscle pain have been reported during bisphosphonate treatment. The onset of pain ranged from a single day to several months. Consider discontinuing therapy in patients who experience severe symptoms; symptoms usually resolve upon discontinuation. Some patients experienced recurrence when rechallenged with same drug or another bisphosphonate; avoid use in patients with a history of these symptoms in association with bisphosphonate therapy.

• Fracture risk: Do not exceed recommended dose or use continuously for >6 months in patients with Paget's disease; risk of osteomalacia or fractures may be increased. Long bones with predominantly lytic lesions may be prone to fracture, particularly in patients unresponsive to treatment.

• Gastrointestinal mucosa irritation: May cause irritation to upper gastrointestinal mucosa. Esophagitis, dysphagia, esophageal ulcers, esophageal erosions, and esophageal stricture (rare) have been reported with oral bisphosphonates; risk increases in patients unable to comply with dosing instructions. Use with caution in patients with dysphagia, esophageal disease, gastritis, duodenitis, or ulcers (may worsen underlying condition). Discontinue use if new or worsening symptoms develop.

• Osteonecrosis of the jaw: Osteonecrosis of the jaw (ONJ), also referred to as medication-related osteonecrosis of the jaw (MRONJ), has been reported in patients receiving bisphosphonates; this has been observed primarily following dental procedures such as tooth extractions and in cancer patients receiving IV bisphosphonates, but has also occurred in patients with postmenopausal osteoporosis and other diagnoses receiving oral bisphosphonates. Risk factors for MRONJ include invasive dental procedures (eg, tooth extraction, dental implants, boney surgery), cancer diagnosis, concomitant chemotherapy, radiotherapy, or corticosteroids; anemia, coagulopathy, infection, ill-fitting dentures, or preexisting dental disease. According to a position paper by the American Association of Maxillofacial Surgeons (AAOMS), MRONJ has been associated with bisphosphonate and other antiresorptive agents (denosumab), and antiangiogenic agents (eg, bevacizumab, sunitinib) used for the treatment of osteoporosis or malignancy. The manufacturer’s labeling states that discontinuing bisphosphonates in patients requiring invasive dental procedures may reduce the risk of ONJ and clinical judgment should guide the decision. However, the AAOMS suggests there is currently no evidence that interrupting oral bisphosphonate therapy alters the risk of ONJ following tooth extraction, and that in patients receiving oral bisphosphonates for <4 years who have no clinical risk factors, no alternations or delay in any procedure common to oral/maxillofacial surgeons, periodontists, and other dental providers is necessary (special considerations apply to patients receiving dental implants). Conversely, in patients receiving oral bisphosphonates for >4 years or in patients receiving oral bisphosphonates for <4 years who have also taken corticosteroids or antiangiogenic medications concomitantly, the AAOMS recommends considering a 2-month drug free period prior to invasive dental procedures (recommendation based on a theoretical benefit). Patients developing ONJ during therapy should receive care by an oral surgeon (AAOMS [Ruggiero 2014]). According to the manufacturer, discontinuation of the bisphosphonate therapy should be considered (based on risk/benefit evaluation) in patients who develop ONJ.

Disease-related concerns:

• Enterocolitis: Use with caution in patients with enterocolitis; diarrhea has been reported at high doses and therapy may need to be withheld.

• Renal impairment: Use with caution in patients with renal impairment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Bone mineralization: May retard mineralization of bone; treatment may need delayed or interrupted until callus is present.

• Calcium/vitamin D intake: Ensure adequate calcium and vitamin D intake.

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

Comments:
-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 Guidelines:
-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.

Comments:
-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.

Uses:
-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.

Total Hip Replacement:
-20 mg/kg/day orally once a day, for 1 month before and 3 months after surgery (4 months total).

Spinal Cord Injury:
-20 mg/kg/day orally once a day, for 2 weeks followed by 10 mg/kg/day for 10 weeks (12 weeks total).

Comment:
-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.

Uses: Prevention and treatment of heterotopic ossification following total hip replacement or due to 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).

Spinal Cord Injury:
-20 mg/kg/day orally once a day, for 2 weeks followed by 10 mg/kg/day for 10 weeks (12 weeks total).

Comment:
-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.

Uses: Prevention and treatment of heterotopic ossification following total hip replacement or due to spinal cord injury.