Didronel tablets contain either 200 mg or 400 mg of etidronate disodium, the disodium salt of (1-hydroxyethylidene) diphosphonic acid, for oral administration. This compound, also known as EHDP, regulates bone metabolism. It is a white powder, highly soluble in water, with a molecular weight of 250 and the following structural formula:

Inactive Ingredients: Each tablet contains magnesium stearate, microcrystalline cellulose, and starch.

Last updated on RxList: 10/3/2008

Didronel 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. Didronel is not approved for the treatment of osteoporosis.

Paget's Disease: Didronel is indicated for the treatment of symptomatic Paget's disease of bone. Didronel therapy usually arrests or significantly impedes the disease process as evidenced by:

--Symptomatic relief, including decreased pain and/or increased mobility (experienced by 3 out of 5 patients).

--Reductions in serum alkaline phosphatase and urinary hydroxyproline levels (30% or more in 4 out of 5 patients).

--Histomorphometry showing reduced numbers of osteoclasts and osteoblasts, and more lamellar bone formation.

--Bone scans showing reduced radionuclide uptake at pagetic lesions.

In addition, reductions in pagetically elevated cardiac output and skin temperature have been observed in some patients.

In many patients, the disease process will be suppressed for a period of at least 1 year following cessation of therapy. The upper limit of this period has not been determined.

The effects of the Didronel treatment in patients with asymptomatic Paget's disease have not been studied. However, Didronel treatment of such patients may be warranted if extensive involvement threatens irreversible neurologic damage, major joints, or major weight-bearing bones.

Heterotopic Ossification: Didronel is indicated in the prevention and treatment of heterotopic ossification following total hip replacement or due to spinal cord injury.

Didronel reduces the incidence of clinically important heterotopic bone by about two-thirds. Among those patients who form heterotopic bone, Didronel retards the progression of immature lesions and reduces the severity by at least half. Follow-up data (at least 9 months posttherapy) suggest these benefits persist.

In total hip replacement patients, Didronel does not promote loosening of the prosthesis or impede trochanteric reattachment.

In spinal cord injury patients, Didronel does not inhibit fracture healing or stabilization of the spine.

Didronel should be taken as a single, oral dose. However, should gastrointestinal discomfort occur, the dose may be divided. To maximize absorption, patients should avoid taking the following items within two hours of dosing:

--Food, especially food high in calcium, such as milk or milk products.

--Vitamins with mineral supplements or antacids which are high in metals such as calcium, iron, magnesium, or aluminum.

Paget's Disease: Initial Treatment Regimens: 5 to 10 mg/kg/day, not to exceed 6 months, or 11 to 20 mg/kg/day, not to exceed 3 months.

The recommended initial dose is 5 mg/kg/day for a period not to exceed 6 months. Doses above 10 mg/kg/day should be reserved for when 1) lower doses are ineffective or 2) there is an overriding need to suppress rapid bone turnover (especially when irreversible neurologic damage is possible) or reduce elevated cardiac output. Doses in excess of 20 mg/kg/day are not recommended.

Retreatment Guidelines: Retreatment should be initiated only after 1) a Didronel-free period of at least 90 days and 2) there is biochemical, symptomatic or other evidence of active disease process. It is advisable to monitor patients 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 for retreatment. If not, consideration should be given to increasing the dose within the recommended guidelines.

Heterotopic Ossification: The following treatment regimens have been shown to be effective:

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

--Spinal Cord Injured Patients: 20 mg/kg/day for 2 weeks followed by 10 mg/kg/day for 10 weeks (12 weeks total). Didronel therapy should begin as soon as medically feasible following the injury, preferably prior to evidence of heterotopic ossification.

Retreatment has not been studied.

Didronel is available as 200-mg, white, rectangular tablets with "P & G" on one face and "402" on the other.

NDC 0149-0405-60 bottle of 60

400-mg, white, scored, capsule-shaped tablets with "N E" on one face and "406" on the other.

NDC 0149-0406-60 bottle of 60

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]

Mfg. by: Norwich Pharmaceuticals, Inc. North Norwich, NY 13814. Dist. by: Procter & Gamble Pharmaceuticals, Inc. TM Owner, Cincinnati, OH 45202. REVISED OCTOBER 2007. FDA Rev date: 1/9/2006

Last updated on RxList: 10/3/2008

The incidence of gastrointestinal complaints (diarrhea, nausea) is the same for Didronel at 5 mg/kg/day as for placebo, about 1 patient in 15. At 10 to 20 mg/kg/day the incidence may increase to 2 or 3 in 10. These complaints are often alleviated by dividing the total daily dose.

Paget's Disease: In Paget's patients, increased or recurrent bone pain at pagetic sites, and/or the onset of pain at previously asymptomatic sites has been reported. At 5 mg/kg/day about 1 patient in 10 (versus 1 in 15 in the placebo group) report these phenomena. At higher doses the incidence rises to about 2 in 10. When therapy continues, pain resolves in some patients but persists in others.

Heterotopic Ossification: No specific adverse reactions.

Worldwide Postmarketing Experience: The worldwide postmarketing experience for etidronate disodium reflects its use in the following approved indications: Paget's disease, heterotopic ossification, and hypercalcemia of malignancy. It also reflects the use of etidronate disodium for osteoporosis where approved in countries outside the US. Other adverse events that have been reported and were thought to be possibly related to etidronate disodium include the following: alopecia; arthropathies, including arthralgia and arthritis; bone fracture; esophagitis; glossitis; hypersensitivity reactions, including angioedema, follicular eruption, macular rash, maculopapular rash, pruritus, a single case of Stevens-Johnson syndrome, and urticaria; osteomalacia; neuropsychiatric events, including amnesia, confusion, depression, and hallucination; and paresthesias.

In patients receiving etidronate disodium, there have been rare reports of agranulocytosis, pancytopenia, and a report of leukopenia with recurrence on rechallenge. In addition, there have been rare reports of exacerbation of asthma. Exacerbation of existing peptic ulcer disease has been reported in a few patients. In one patient, perforation also occurred.

In osteoporosis clinical trials, headache, gastritis, leg cramps, and arthralgia occurred at a significantly greater incidence in patients who received etidronate as compared with those who received placebo.

There have been isolated reports of patients experiencing increases in their prothrombin times when etidronate was added to warfarin therapy. The majority of these reports concerned variable elevations in prothrombin times without clinically significant sequelae. Although the relevance of these reports and any mechanism of coagulation alterations is unclear, patients on warfarin should have their prothrombin time monitored.

Last updated on RxList: 10/3/2008

Paget's Disease: In Paget's patients the response to therapy may be of slow onset and continue for months after Didronel therapy is discontinued. Dosage should not be increased prematurely. A 90-day drug-free interval should be provided between courses of therapy.

Heterotopic Ossification: No specific warnings.

General

Patients should maintain an adequate nutritional status, particularly an adequate intake of calcium and vitamin D.

Therapy has been withheld from some patients with enterocolitis since diarrhea may be experienced, particularly at higher doses.

Didronel is not metabolized and is excreted intact via the kidney. Hyperphosphatemia may occur at doses of 10 to 20 mg/kg/day, apparently as a result of drug-related increases in tubular reabsorption of phosphate. Serum phosphate levels generally return to normal 2 to 4 weeks posttherapy. There is no experience to specifically guide treatment in patients with impaired renal function. Didronel dosage should be reduced when reductions in glomerular filtration rates are present. Patients with renal impairment should be closely monitored. In approximately 10% of patients in clinical trials of Didronel® I. V. Infusion (etidronate disodium) for hypercalcemia of malignancy, occasional, mild-to-moderate abnormalities in renal function (increases of > 0.5 mg/dl serum creatinine) were observed during or immediately after treatment.

Didronel suppresses bone turnover, and may retard mineralization of osteoid laid down during the bone accretion process. These effects are dose and time dependent. Osteoid, which may accumulate noticeably at doses of 10 to 20 mg/kg/day, mineralizes normally posttherapy. In patients with fractures, especially of long bones, it may be advisable to delay or interrupt treatment until callus is evident.

Osteonecrosis, primarily in the jaw, has been reported in patients treated with bisphosphonates. Most cases have been in cancer patients undergoing dental procedures such as tooth extraction, but some have occurred in patients with postmenopausal osteoporosis or other diagnoses. Most reported cases have been in patients treated with bisphosphonates intravenously but some have been in patients treated orally.

For patients requiring dental procedures, there are no data available to suggest whether discontinuation of bisphosphonate treatment, prior to the procedure, reduces the risk of osteonecrosis of the jaw. Clinical judgment should guide the management plan of each patient based on individual benefit/risk assessment.

Musculoskeletal Pain: In postmarketing experience, there have been infrequent reports of severe and occasionally incapacitating bone, joint, and/or muscle pain in patients taking bisphosphonates (see ADVERSE REACTIONS). 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 medication. A subset had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate.

Paget's Disease: In Paget's patients, treatment regimens exceeding the recommended (see DOSAGE AND ADMINISTRATION) daily maximum dose of 20 mg/kg or continuous administration of medication for periods greater than 6 months may be associated with osteomalacia and an increased risk of fracture.

Long bones predominantly affected by lytic lesions, particularly in those patients unresponsive to Didronel therapy, may be especially prone to fracture.

Patients with predominantly lytic lesions should be monitored radiographically and biochemically to permit termination of Didronel in those patients unresponsive to treatment.

Carcinogenesis: Long-term studies in rats have indicated that Didronel is not carcinogenic.

Pregnancy: Teratogenic Effects: Pregnancy Category C. In teratology and developmental toxicity studies conducted in rats and rabbits treated with dosages of up to 100 mg/kg (5 to 20 times the clinical dose), no adverse or teratogenic effects have been observed in the offspring. Etidronate disodium has been shown to cause skeletal abnormalities in rats when given at oral dose levels of 300 mg/kg (15 to 60 times the human dose). Other effects on the offspring (including decreased live births) are at dosages that cause significant toxicity in the parent generation and are 25 to 200 times the human dose. The skeletal effects are thought to be the result of the pharmacological effects of the drug on bone.

Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over periods of weeks to years. The amount of bisphosphonate incorporation into adult bone, and hence, the amount available for release back into the systemic circulation, is directly related to the dose and duration of bisphosphonate use. There are no data on fetal risk in humans. However, there is a theoretical risk of fetal harm, predominantly skeletal, 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 studied.

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

Nursing Mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Didronel is administered to a nursing woman.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established. Pediatric patients have been treated with Didronel, at doses recommended for adults, to prevent heterotopic ossifications or soft tissue calcifications. A rachitic syndrome has been reported infrequently at doses of 10 mg/kg/day and more for prolonged periods approaching or exceeding a year. The epiphyseal radiologic changes associated with retarded mineralization of new osteoid and cartilage, and occasional symptoms reported, have been reversible when medication is discontinued.

Geriatric Use: Clinical studies of Didronel did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken when prescribing this drug therapy. As stated in PRECAUTIONS, Didronel dosage should be reduced when reductions in glomerular filtration rates are present. In addition, patients with renal impairment should be closely monitored.

Last updated on RxList: 10/3/2008

Clinical experience with acute Didronel overdosage is extremely limited. Decreases in serum calcium following substantial overdosage may be expected in some patients. Signs and symptoms of hypocalcemia also may occur in some of these patients. Some patients may develop vomiting. In one event, an 18-year-old female who ingested an estimated single dose of 4000 to 6000 mg (67 to 100 mg/kg) of Didronel was reported to be mildly hypocalcemic (7.52 mg/dl) and experienced paresthesia of the fingers. Hypocalcemia resolved 6 hours after lavage and treatment with intravenous calcium gluconate. A 92-year-old female who accidentally received 1600 mg of etidronate disodium per day for 3.5 days experienced marked diarrhea and required treatment for electrolyte imbalance. Orally administered etidronate disodium may cause hematologic abnormalities in some patients (see ADVERSE REACTIONS).

Etidronate disodium suppresses bone turnover and may retard mineralization of osteoid laid down during the bone accretion process. These effects are dose and time dependent. Osteoid which may accumulate noticeably at doses of 10 to 20 mg/kg/day of chronic, continuous dosing mineralizes normally posttherapy.

Prolonged continuous treatment (chronic overdosage) has been reported to cause nephrotic syndrome and fracture.

Gastric lavage may remove unabsorbed drug. Standard procedures for treating hypocalcemia, including the administration of Ca⁺⁺ intravenously, would be expected to restore physiologic amounts of ionized calcium and relieve signs and symptoms of hypocalcemia. Such treatment has been effective.

Didronel tablets are contraindicated in patients with known hypersensitivity to etidronate disodium or in patients with clinically overt osteomalacia.

Last updated on RxList: 10/3/2008

Didronel acts primarily on bone. It can inhibit the formation, growth, and dissolution of hydroxyapatite crystals and their amorphous precursors by chemisorption to calcium phosphate surfaces. Inhibition of crystal resorption occurs at lower doses than are required to inhibit crystal growth. Both effects increase as the dose increases.

Didronel is not metabolized. The amount of drug absorbed after an oral dose is approximately 3%. In normal subjects, plasma half-life (t_1/2) of etidronate, based on non- compartmental pharmacokinetics is 1 to 6 hours. Within 24 hours, approximately half the absorbed dose is excreted in urine; the remainder is distributed to bone compartments from which it is slowly eliminated. Animal studies have yielded bone clearance estimates up to 165 days. In humans, the residence time on bone may vary due to such factors as specific metabolic condition and bone type. Unabsorbed drug is excreted intact in the feces. Preclinical studies indicate etidronate disodium does not cross the blood-brain barrier.

Didronel therapy does not adversely affect serum levels of parathyroid hormone or calcium.

Paget's Disease: Paget's disease of bone (osteitis deformans) is an idiopathic, progressive disease characterized by abnormal and accelerated bone metabolism in one or more bones. Signs and symptoms may include bone pain and/or deformity, neurologic disorders, elevated cardiac output and other vascular disorders, and increased serum alkaline phosphatase and/or urinary hydroxyproline levels. Bone fractures are common in patients with Paget's disease.

Didronel slows accelerated bone turnover (resorption and accretion) in pagetic lesions and, to a lesser extent, in normal bone. This has been demonstrated histologically, scintigraphically, biochemically, and through calcium kinetic and balance studies. Reduced bone turnover is often accompanied by symptomatic improvement, including reduced bone pain. Also, the incidence of pagetic fractures may be reduced, and elevated cardiac output and other vascular disorders may be improved by Didronel therapy.

Heterotopic Ossification: Heterotopic ossification, also referred to as myositis ossificans (circumscripta, progressiva or traumatica), ectopic calcification, periarticular ossification, or paraosteoarthropathy, is characterized by metaplastic osteogenesis. It usually presents with signs of localized inflammation or pain, elevated skin temperature, and redness. When tissues near joints are involved, functional loss may also be present.

Heterotopic ossification may occur for no known reason as in myositis ossificans progressiva or may follow a wide variety of surgical, occupational, and sports trauma (e.g., hip arthroplasty, spinal cord injury, head injury, burns, and severe thigh bruises). Heterotopic ossification has also been observed in non-traumatic conditions (e.g., infections of the central nervous system, peripheral neuropathy, tetanus, biliary cirrhosis, Peyronie's disease, as well as in association with a variety of benign and malignant neoplasms).

Clinical trials have demonstrated the efficacy of Didronel in heterotopic ossification following total hip replacement, or due to spinal cord injury.

--Heterotopic ossification complicating total hip replacement typically develops radiographically 3 to 8 weeks postoperatively in the pericapsular area of the affected hip joint. The overall incidence is about 50%; about one-third of these cases are clinically significant.

--Heterotopic ossification due to spinal cord injury typically develops radiographically 1 to 4 months after injury. It occurs below the level of injury, usually at major joints. The overall incidence is about 40%; about one-half of these cases are clinically significant.

Didronel chemisorbs to calcium hydroxyapatite crystals and their amorphous precursors, blocking the aggregation, growth, and mineralization of these crystals. This is thought to be the mechanism by which Didronel prevents or retards heterotopic ossification. There is no evidence Didronel affects mature heterotopic bone.

Last updated on RxList: 10/3/2008

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last updated on RxList: 10/3/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

ETIDRONATE DISODIUM - ORAL

(eh-TIDD-row-nate dye-SO-dee-um)

COMMON BRAND NAME(S): Didronel

USES: Etidronate is used to treat a certain type of bone disease called Paget's disease. This medication may also be used to treat bone problems that may occur after hip replacement or spinal cord injury. Etidronate belongs to a class of drugs known as bisphosphonates. It works by slowing bone loss, thereby helping your bones grow stronger and less likely to break.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

Etidronate may also be used for other bone problems such as brittle bones (osteoporosis) caused by the long-term use of corticosteroid medications (e.g., prednisone). This medication may also used to treat high blood calcium levels (hypercalcemia) that may occur with cancer.

HOW TO USE: Take this medication by mouth without food, on an empty stomach 2 hours before a meal, usually once daily or as directed by your doctor.

Take with a full glass of water (6 to 8 ounces/180 to 240 milliliters) unless your doctor directs you otherwise. After taking etidronate, do not lie down for at least 30 minutes.

Avoid taking etidronate 2 hours before or 2 hours after food or any products containing iron, magnesium, calcium, or aluminum (e.g., antacids, laxatives, vitamins, dairy products). Doing so may cause less drug to be absorbed by your body. If stomach upset occurs, it may help to divide your dose and take part of it 2 or more times during the day instead of in one daily dose. Talk to your doctor about the correct way to do this.

It is important to get enough vitamin D and calcium in your diet while taking this medication. Consult your doctor or pharmacist for more details.

For Paget's disease and bone problems after hip replacement or spinal cord injury, treatment with this medication usually lasts 3-6 months. For Paget's disease, your doctor may direct you to repeat treatment but start the repeat treatment at least 90 days after your last course of treatment.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time(s) each day.

SIDE EFFECTS: Nausea, stomach upset, diarrhea, or headache 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 immediately if any of these unlikely but serious side effects occur: increased or severe bone/joint/muscle pain, jaw pain, painful swallowing, vomiting, leg cramps, skin numbness/tingling, stomach/abdominal pain, vomit that is bloody or looks like coffee grounds, black/tarry stools, hair loss, mental/mood changes (e.g., confusion, depression), bent bones, easily broken bones.

Tell your doctor immediately if any of these rare but very serious side effects occur: signs of infection (e.g., fever, persistent sore throat), unusual bruising/bleeding, unusual tiredness.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, 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.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking etidronate, tell your doctor or pharmacist if you are allergic to it; or to other bisphosphonates such as tiludronate; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: a condition that causes soft/painful bones and weak/stiff muscles (osteomalacia).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney disease, asthma, difficult/painful swallowing, history of ulcer in the esophagus/stomach, colitis, digestive disorders, broken bones, high phosphate levels, low calcium levels, vitamin D deficiency.

Infrequently, serious jawbone problems (osteonecrosis) have occurred in people taking this medication. Most people were also using other medications or had conditions which might have actually caused the jawbone problem. If you have cancer, anemia, blood clotting disorders, infections/other diseases of the mouth, or poor dental hygiene, see your dentist for a full examination/treatment before you start etidronate. Make sure your dentist knows your entire medical history, including any cancer radiation treatments, and also knows of all the medications you are using, especially corticosteroids such as prednisone, cancer chemotherapy, and etidronate. Consult your dentist for more details.

Kidney function declines as you grow older. This medication is removed by the kidneys. Therefore, elderly people may be at greater risk for side effects while using this drug.

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. Consult your doctor before breast-feeding.

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.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: "blood thinners" (warfarin), vitamins that contain minerals, calcium supplements, laxatives that contain magnesium, antacids, aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs such as indomethacin, ibuprofen).

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: vomiting, diarrhea, numb/tingling fingers, muscle spasms, seizures.

NOTES: Do not share this medication with others.

Lifestyle changes that help promote healthy bones include increasing weight-bearing exercise, stopping smoking, limiting alcohol, and eating well-balanced meals that contain adequate calcium and vitamin D. Since you may also need to take calcium and vitamin D supplements and make lifestyle changes, consult your doctor for specific advice.

Laboratory and/or medical tests (e.g., calcium, phosphate, and magnesium levels, albumin, serum creatinine) will be performed 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. 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 between 59 to 86 degrees F (15 to 30 degrees C) away from light and moisture. Do not store in the bathroom. 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 July 2008 Copyright(c) 2008 First DataBank, Inc.