Reclast

Q: Who makes Reclast?

Reclast is listed by 1 labeler in the FDA NDC directory, including Sandoz Inc.

zoledronic acid · Injection, Solution · Intravenous

Uses

Reclast is a bisphosphonate indicated for:
• Treatment and prevention of postmenopausal osteoporosis ( 1.1 , 1.2 )
• Treatment to increase bone mass in men with osteoporosis ( 1.3 )
• Treatment and prevention of glucocorticoid-induced osteoporosis ( 1.4 )
• Treatment of Paget’s disease of bone in men and women ( 1.5 ) Limitations of Use Optimal duration of use has not been determined. For patients at low-risk for fracture, consider drug discontinuation after 3 to 5 years of use ( 1.6 ) 1.1 Treatment of Osteoporosis in Postmenopausal Women Reclast is indicated for treatment of osteoporosis in postmenopausal women. In postmenopausal women with osteoporosis, diagnosed by bone mineral density (BMD) or prevalent vertebral fracture, Reclast reduces the incidence of fractures (hip, vertebral, and non-vertebral osteoporosis-related fractures). In patients at high risk of fracture, defined as a recent low-trauma hip fracture, Reclast reduces the incidence of new clinical fractures [see Clinical Studies ( 14.1 )]. 1.2 Prevention of Osteoporosis in Postmenopausal Women Reclast is indicated for prevention of osteoporosis in postmenopausal women [see Clinical Studies ( 14.2 )]. 1.3 Osteoporosis in Men Reclast is indicated for treatment to increase bone mass in men with osteoporosis [see Clinical Studies ( 14.3 )]. 1.4 Glucocorticoid-Induced Osteoporosis Reclast is indicated for the treatment and prevention of glucocorticoid-induced osteoporosis in men and women who are either initiating or continuing systemic glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and who are expected to remain on glucocorticoids for at least 12 months [see Clinical Studies ( 14.4 )]. 1.5 Paget's Disease of Bone Reclast is indicated for treatment of Paget's disease of bone in men and women. Treatment is indicated in patients with Paget’s disease of bone with elevations in serum alkaline phosphatase of two times or higher than the upper limit of the age-specific normal reference range, or those who are symptomatic, or those at risk for complications from their disease [see Clinical Studies ( 14.5 )]. 1.6 Important Limitations of Use The safety and effectiveness of Reclast for the treatment of osteoporosis is based on clinical data of three years duration. The optimal duration of use has not been determined. All patients on bisphosphonate therapy should have the need for continued therapy reevaluated on a periodic basis. Patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use. Patients who discontinue therapy should have their risk for fracture reevaluated periodically.

Dosage and administration

Infusion given intravenously over no less than 15 minutes:
• Treatment of postmenopausal osteoporosis ( 2.2 ); treatment to increase bone mass in men with osteoporosis ( 2.4 ): treatment and prevention of glucocorticoid-induced osteoporosis ( 2.5 ): 5 mg once a year
• Prevention of postmenopausal osteoporosis: 5 mg once every 2 years ( 2.3 )
• Treatment of Paget’s disease of bone: a single 5 mg infusion. Patients should receive 1500 mg elemental calcium and 800 international units vitamin D daily ( 2.6 ) 2.1 Important Administration Instructions Reclast injection must be administered as an intravenous infusion over no less than 15 minutes.
• Patients must be appropriately hydrated prior to administration of Reclast [see Warnings and Precautions ( 5.3 )] .
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
• Intravenous infusion should be followed by a 10 mL normal saline flush of the intravenous line.
• Administration of acetaminophen following Reclast administration may reduce the incidence of acute-phase reaction symptoms. 2.2 Treatment of Osteoporosis in Postmenopausal Women The recommended regimen is a 5 mg infusion once a year given intravenously over no less than 15 minutes. 2.3 Prevention of Osteoporosis in Postmenopausal Women The recommended regimen is a 5 mg infusion given once every 2 years intravenously over no less than 15 minutes. 2.4 Osteoporosis in Men The recommended regimen is a 5 mg infusion once a year given intravenously over no less than 15 minutes. 2.5 Treatment and Prevention of Glucocorticoid-Induced Osteoporosis The recommended regimen is a 5 mg infusion once a year given intravenously over no less than 15 minutes. 2.6 Treatment of Paget’s Disease of Bone The recommended dose is a 5 mg infusion. The infusion time must not be less than 15 minutes given over a constant infusion rate. Re-treatment of Paget’s Disease After a single treatment with Reclast in Paget’s disease an extended remission period is observed. Specific re-treatment data are not available. However, re-treatment with Reclast may be considered in patients who have relapsed, based on increases in serum alkaline phosphatase, or in those patients who failed to achieve normalization of their serum alkaline phosphatase, or in those patients with symptoms, as dictated by medical practice. 2.7 Laboratory Testing and Oral Examination Prior to Administration
• Prior to administration of each dose of Reclast, obtain a serum creatinine and creatinine clearance should be calculated based on actual body weight using Cockcroft-Gault formula before each Reclast dose. Reclast is contraindicated in patients with creatinine clearance less than 35 mL/min and in those with evidence of acute renal impairment. A 5 mg dose of Reclast administered intravenously is recommended for patients with creatinine clearance greater than or equal to 35 mL/min. There are no safety or efficacy data to support the adjustment of the Reclast dose based on baseline renal function. Therefore, no dose adjustment is required in patients with creatinine clearance greater than or equal to 35 mL/min [see Contraindications ( 4 ), Warnings and Precautions ( 5.3 )].
• A routine oral examination should be performed by the prescriber prior to initiation of Reclast treatment [see Warnings and Precautions ( 5.4 )]. 2.8 Calcium and Vitamin D Supplementation
• Instruct patients being treated for Paget’s disease of bone on the importance of calcium and vitamin D supplementation in maintaining serum calcium levels, and on the symptoms of hypocalcemia. All patients should take 1500 mg elemental calcium daily in divided doses (750 mg two times a day, or 500 mg three times a day) and 800 international units vitamin D daily, particularly in the 2 weeks following Reclast administration [see Warnings and Precautions ( 5.2 )] .
• Instruct patients being treated for osteoporosis to take supplemental calcium and vitamin D if their dietary intake is inadequate. An average of at least 1200 mg calcium and 800-1000 international units vitamin D daily is recommended. 2.9 Method of Administration The Reclast infusion time must not be less than 15 minutes given over a constant infusion rate. The intravenous infusion should be followed by a 10 mL normal saline flush of the intravenous line. Reclast solution for infusion must not be allowed to come in contact with any calcium or other divalent cation-containing solutions, and should be administered as a single intravenous solution through a separate vented infusion line. If refrigerated, allow the refrigerated solution to reach room temperature before administration. After opening, the solution is stable for 24 hours at 2°C to 8°C (36°F to 46°F) [see How Supplied/Storage and Handling ( 16 )].

Dosage forms and strengths

5 mg in a 100 mL ready to infuse solution. 5 mg in a 100 mL ready-to-infuse solution ( 3 )

Contraindications

Reclast is contraindicated in patients with the following conditions:
• Hypocalcemia [see Warnings and Precautions ( 5.2 )]
• Creatinine clearance less than 35 mL/min and in those with evidence of acute renal impairment due to an increased risk of renal failure [see Warnings and Precautions ( 5.3 )] .
• Known hypersensitivity to zoledronic acid or any components of Reclast. Hypersensitivity reactions, including urticaria, angioedema, and anaphylactic reaction/shock have been reported [see Adverse Reactions ( 6.2 )].
• Hypocalcemia ( 4 )
• Patients with creatinine clearance less than 35 mL/min and in those with evidence of acute renal impairment ( 4 , 5.3 )
• Hypersensitivity to any component of Reclast ( 4 , 6.2 )

Warnings and precautions

• Products Containing Same Active Ingredient: Patients receiving Zometa should not receive Reclast ( 5.1 )
• Hypocalcemia may worsen during treatment . Patients must be adequately supplemented with calcium and vitamin D ( 5.2 )
• Renal Impairment: A single dose should not exceed 5 mg and the duration of infusion should be no less than 15 minutes. Renal toxicity may be greater in patients with underlying renal impairment or with other risk factors, including advanced age or dehydration. Monitor creatinine clearance before each dose ( 2.7 , 5.3 )
• Osteonecrosis of the Jaw (ONJ) has been reported. All patients should have a routine oral exam by the prescriber prior to treatment ( 5.4 )
• Atypical Fractures Including Femoral Fractures have been reported. Patients with thigh or groin pain should be evaluated to rule out a femoral fracture. Risk/benefit of continuing bisphosphonate therapy should be re-evaluated in these patients and interruption of bisphosphonate therapy should be considered ( 5.5 )
• Severe Bone, Joint, and Muscle Pain may occur. Withhold future doses of Reclast if severe symptoms occur ( 5.6 ) 5.1 Drug Products With Same Active Ingredient Reclast contains the same active ingredient found in Zometa, used for oncology indications, and a patient being treated with Zometa should not be treated with Reclast. 5.2 Hypocalcemia and Mineral Metabolism Preexisting hypocalcemia and disturbances of mineral metabolism (e.g., hypoparathyroidism, thyroid surgery, parathyroid surgery; malabsorption syndromes, excision of small intestine) must be effectively treated before initiating therapy with Reclast. Clinical monitoring of calcium and mineral levels (phosphorus and magnesium) is highly recommended for these patients [see Contraindications ( 4 )]. Hypocalcemia following Reclast administration is a significant risk in Paget’s disease. All patients should be instructed about the symptoms of hypocalcemia and the importance of calcium and vitamin D supplementation in maintaining serum calcium levels [see Dosage and Administration ( 2.8 ), Adverse Reactions ( 6.1 ), Patient Counseling Information ( 17 )]. All osteoporosis patients should be instructed on the importance of calcium and vitamin D supplementation in maintaining serum calcium levels [see Dosage and Administration ( 2.8 ), Adverse Reactions ( 6.1 ), Patient Counseling Information ( 17 )]. 5.3 Renal Impairment A single dose of Reclast should not exceed 5 mg and the duration of infusion should be no less than 15 minutes [see Dosage and Administration ( 2 )]. Reclast is contraindicated in patients with creatinine clearance less than 35 mL/min and in those with evidence of acute renal impairment [see Contraindications ( 4 )]. If history or physical signs suggest dehydration, Reclast therapy should be withheld until normovolemic status has been achieved [see Adverse Reactions ( 6.2 )]. Reclast should be used with caution in patients with chronic renal impairment. Acute renal impairment, including renal failure, has been observed following the administration of zoledronic acid, especially in patients with preexisting renal compromise, advanced age, concomitant nephrotoxic medications, concomitant diuretic therapy, or severe dehydration occurring before or after Reclast administration. Acute renal failure (ARF) has been observed in patients after a single administration. Rare reports of hospitalization and/or dialysis or fatal outcome occurred in patients with underlying moderate to severe renal impairment or with any of the risk factors described in this section [see Adverse Reactions ( 6.2 )] . Renal impairment may lead to increased exposure of concomitant medications and/or their metabolites that are primarily renally excreted [see Drug Interactions ( 7.4 )] . Creatinine clearance should be calculated based on actual body weight using Cockcroft-Gault formula before each Reclast dose. Transient increase in serum creatinine may be greater in patients with impaired renal function; interim monitoring of creatinine clearance should be performed in at-risk patients. Elderly patients and those receiving diuretic therapy are at increased risk of acute renal failure. These patients should have their fluid status assessed and be appropriately hydrated prior to administration of Reclast. Reclast should be used with caution with other nephrotoxic drugs [see Drug Interactions ( 7.3 )] . Consider monitoring creatinine clearance in patients at-risk for ARF who are taking concomitant medications that are primarily excreted by the kidney [see Drug Interactions ( 7.4 )]. 5.4 Osteonecrosis of the Jaw Osteonecrosis of the jaw (ONJ) has been reported in patients treated with bisphosphonates, including zoledronic acid. Most cases have been in cancer patients treated with intravenous bisphosphonates undergoing dental procedures. Some cases have occurred in patients with postmenopausal osteoporosis treated with either oral or intravenous bisphosphonates. A routine oral examination should be performed by the prescriber prior to initiation of bisphosphonate treatment. A dental examination with appropriate preventive dentistry should be considered prior to treatment with bisphosphonates in patients with a history of concomitant risk factors (e.g., cancer, chemotherapy, angiogenesis inhibitors, radiotherapy, corticosteroids, poor oral hygiene, preexisting dental disease or infection, anemia, coagulopathy). The risk of ONJ may increase with duration of exposure to bisphosphonates. Concomitant administration of drugs associated with ONJ may increase the risk of developing ONJ. While on treatment, patients with concomitant risk factors should avoid invasive dental procedures if possible. For patients who develop 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.

Side effects

The following clinically significant adverse drug reactions are described elsewhere in the labeling:
• Drugs with Same Active Ingredient [see Warnings and Precautions ( 5.1 )]
• Hypocalcemia and Mineral Metabolism [see Warnings and Precautions ( 5.2 )]
• Renal Impairment [see Warnings and Precautions ( 5.3 )]
• Osteonecrosis of the Jaw [see Warnings and Precautions ( 5.4 )]
• Atypical Fractures Including Femoral Fractures [see Warnings and Precautions ( 5.5 )]
• Musculoskeletal Pain [see Warnings and Precautions ( 5.6 )]
• Patients with Asthma [see Warnings and Precautions ( 5.7 )] The most common adverse reactions (greater than 10%) were pyrexia, myalgia, headache, arthralgia, pain in extremity ( 6.1 ). Other important adverse reactions were flu-like illness, nausea, vomiting, diarrhea ( 6.2 ), and eye inflammation ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Treatment of Osteoporosis in Postmenopausal Women The safety of Reclast in the treatment of postmenopausal osteoporosis was assessed in Study 1, a large, randomized, double-blind, placebo-controlled, multinational study of 7736 postmenopausal women aged 65 to 89 years with osteoporosis, diagnosed by BMD or the presence of a prevalent vertebral fracture. The duration of the trial was three years with 3862 patients exposed to Reclast and 3852 patients exposed to placebo administered once annually as a single 5 mg dose in 100 mL solution infused over at least 15 minutes, for a total of three doses. All women received 1000 to 1500 mg of elemental calcium plus 400 to 1200 international units of vitamin D supplementation per day. The incidence of all-cause mortality was similar between groups: 3.4% in the Reclast group and 2.9% in the placebo group. The incidence of serious adverse events was 29.2% in the Reclast group and 30.1% in the placebo group. The percentage of patients who withdrew from the study due to adverse events was 5.4% and 4.8% for the Reclast and placebo groups, respectively. The safety of Reclast in the treatment of osteoporosis patients with a recent (within 90 days) low-trauma hip fracture was assessed in Study 2, a randomized, double-blind, placebo-controlled, multinational endpoint-driven study of 2127 men and women aged 50 to 95 years; 1065 patients were randomized to Reclast and 1062 patients were randomized to placebo. Reclast was administered once annually as a single 5 mg dose in 100 mL solution infused over at least 15 minutes. The study continued until at least 211 patients had a confirmed clinical fracture in the study population who were followed for an average of approximately 2 years on study drug. Vitamin D levels were not routinely measured but a loading dose of vitamin D (50,000 to 125,000 international units orally or IM) was given to patients and they were started on 1000 to 1500 mg of elemental calcium plus 800 to 1200 international units of vitamin D supplementation per day for at least 14 days prior to the study drug infusions. The incidence of all-cause mortality was 9.6% in the Reclast group and 13.3% in the placebo group. The incidence of serious adverse events was 38.3% in the Reclast group and 41.3% in the placebo group. The percentage of patients who withdrew from the study due to adverse events was 5.3% and 4.7% for the Reclast and placebo groups, respectively. Adverse reactions reported in at least 2% of patients with osteoporosis and more frequently in the Reclast-treated patients than placebo-treated patients in either osteoporosis trial are shown below in Table 1. Table 1. Adverse Reactions Occurring in Greater Than or Equal to 2.0% of Patients with Osteoporosis and More Frequently Than in Placebo-Treated Patients Abbreviation: IV, intravenous or intravenously. Study 1 Study 2 System Organ Class 5 mg IV Reclast once per year % (N = 3862) Placebo once per year % (N = 3852) 5 mg IV Reclast once per year % (N = 1054) Placebo once per year % (N = 1057) Blood and the Lymphatic System Disorders Anemia 4.4 3.6 5.3 5.2 Metabolism and Nutrition Disorders Dehydration 0.6 0.6 2.5 2.3 Anorexia 2.0 1.1 1.0 1.0 Nervous System Disorders Headache 12.4 8.1 3.9 2.5 Dizziness 7.6 6.7 2.0 4.0 Ear and Labyrinth Disorders Vertigo 4.3 4.0 1.3 1.7 Cardiac Disorders Atrial fibrillation 2.4 1.9 2.8 2.6 Vascular Disorders Hypertension 12.7 12.4 6.8 5.4 Gastrointestinal Disorders Nausea 8.5 5.2 4.5 4.5 Diarrhea 6.0 5.6 5.2 4.7 Vomiting 4.6 3.2 3.4 3.4 Abdominal pain upper 4.6 3.1 0.9 1.5 Dyspepsia 4.3 4.0 1.7 1.6 Musculoskeletal, Connective Tissue and Bone Disorders Arthralgia 23.8 20.4 17.9 18.3 Myalgia 11.7 3.7 4.9 2.7 Pain in extremity 11.3 9.9 5.9 4.8 Shoulder pain 6.9 5.6 0.0 0.0 Bone pain 5.8 2.3 3.2 1.0 Neck pain 4.4 3.8 1.4 1.1 Muscle spasms 3.7 3.4 1.5 1.7 Osteoarthritis 9.1 9.7 5.7 4.5 Musculoskeletal pain 0.4 0.3 3.1 1.2 General Disorders and Administrative-Site Conditions Pyrexia 17.9 4.6 8.7 3.1 Influenza-like illness 8.8 2.7 0.8 0.4 Fatigue 5.4 3.5 2.1 1.2 Chills 5.4 1.0 1.5 0.5 Asthenia 5.3 2.9 3.2 3.0 Peripheral edema 4.6 4.2 5.5 5.3 Pain 3.3 1.3 1.5 0.5 Malaise 2.0 1.0 1.1 0.5 Hyperthermia 0.3 < 0.1 2.3 0.3 Chest Pain 1.3 1.1 2.4 1.8 Investigations Creatinine renal clearance decreased 2.0 2.4 2.1 1.7 Renal Impairment Treatment with intravenous bisphosphonates, including zoledronic acid, has been associated with renal impairment manifested as deterioration in renal function (i.e., increased serum creatinine) and in rare cases, acute renal failure.

Drug interactions

No in vivo drug interaction studies have been performed for Reclast. In vitro and ex vivo studies showed low affinity of zoledronic acid for the cellular components of human blood. In vitro mean zoledronic acid protein binding in human plasma ranged from 28% at 200 ng/mL to 53% at 50 ng/mL. In vivo studies showed that zoledronic acid is not metabolized, and is excreted into the urine as the intact drug.
• Aminoglycosides: May lower serum calcium for prolonged periods ( 7.1 )
• Loop Diuretics: May increase risk of hypocalcemia ( 7.2 )
• Nephrotoxic Drugs: Use with caution ( 7.3 )
• Drugs Primarily Excreted by the Kidney: Exposure may be increased with renal impairment. Monitor serum creatinine in patients at risk ( 7.4 ) 7.1 Aminoglycosides Caution is advised when bisphosphonates, including zoledronic acid, are administered with aminoglycosides, since these agents may have an additive effect to lower serum calcium level for prolonged periods. This effect has not been reported in zoledronic acid clinical trials. 7.2 Loop Diuretics Caution should also be exercised when Reclast is used in combination with loop diuretics due to an increased risk of hypocalcemia. 7.3 Nephrotoxic Drugs Caution is indicated when Reclast is used with other potentially nephrotoxic drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs). 7.4 Drugs Primarily Excreted by the Kidney Renal impairment has been observed following the administration of zoledronic acid in patients with preexisting renal compromise or other risk factors [see Warnings and Precautions ( 5.3 )] . In patients with renal impairment, the exposure to concomitant medications that are primarily renally excreted (e.g., digoxin) may increase. Consider monitoring serum creatinine in patients at risk for renal impairment who are taking concomitant medications that are primarily excreted by the kidney.

Use in specific populations

• Pregnancy: Discontinue when pregnancy is recognized ( 8.1 )
• Pediatric Use: Not indicated for use in pediatric patients ( 8.4 )
• Geriatric Use: Special care to monitor renal function ( 8.5 ) 8.1 Pregnancy Risk Summary Available data on the use of Reclast in pregnant women are insufficient to inform a drug-associated risk of adverse maternal or fetal outcomes. Discontinue Reclast when pregnancy is recognized. In animal reproduction studies, daily subcutaneous administration of zoledronic acid to pregnant rats during organogenesis resulted in increases in fetal skeletal, visceral, and external malformations, decreases in postimplantation survival, and decreases in viable fetuses and fetal weight starting at doses equivalent to 2 times the recommended human 5 mg intravenous dose (based on AUC). Subcutaneous administration of zoledronic acid to rabbits during organogenesis did not cause adverse fetal effects at up to 0.4 times the human 5 mg intravenous dose (based on body surface area, mg/m 2 ), but resulted in maternal mortality and abortion associated with hypocalcemia starting at doses equivalent to 0.04 times the human 5 mg intravenous dose. Subcutaneous dosing of female rats from before mating through gestation and lactation and allowed to deliver caused maternal dystocia and periparturient mortality, increases in stillbirths and neonatal deaths, and reduced pup body weight starting at doses equivalent to 0.1 times the human 5 mg intravenous dose (based on AUC) ( see Data ). Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over a period of years. The amount of bisphosphonate incorporated into adult bone, and available for release into the systemic circulation is directly related to the dose and duration of bisphosphonate use. Consequently, based on the mechanism of action of bisphosphonates, there is a potential 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 the risk has not been studied. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Data Animal Data In pregnant rats given daily subcutaneous doses of zoledronic acid of 0.1, 0.2, or 0.4 mg/kg during organogenesis, fetal skeletal, visceral, and external malformations, increases in pre-and post-implantation loss, and decreases in viable fetuses and fetal weight were observed at 0.2 and 0.4 mg/kg/day (equivalent to 2 and 4 times the human 5 mg intravenous dose, based on AUC). Adverse fetal skeletal effects at 0.4 mg/kg/day (4 times the human 5 mg dose) included unossified or incompletely ossified bones, thickened, curved or shortened bones, wavy ribs, and shortened jaw. Other adverse fetal effects at this dose included reduced lens, rudimentary cerebellum, reduction or absence of liver lobes, reduction of lung lobes, vessel dilation, cleft palate, and edema. Skeletal variations were observed in all groups starting at 0.1 mg/kg/day (1.2 times the human 5 mg dose). Signs of maternal toxicity, including reduced body weight and food consumption were observed at 0.4 mg/kg/day (4 times the human 5 mg dose). In pregnant rabbits given daily subcutaneous doses of zoledronic acid of 0.01, 0.03, or 0.1 mg/kg during gestation, no adverse fetal effects were observed up to 0.1 mg/kg/day (0.4 times the human 5 mg intravenous dose, based on body surface area, mg/m 2 ). Maternal mortality and abortion were observed in all dose groups (starting at 0.04 times the human 5 mg dose). Adverse maternal effects were associated with drug-induced hypocalcemia. In female rats given daily subcutaneous doses of 0.01, 0.03, or 0.1 mg/kg, beginning 15 days before mating and continuing through gestation, parturition and lactation, dystocia and periparturient mortality were observed in pregnant rats allowed to deliver starting at 0.01 mg/kg/day (0.1 times the human 5 mg intravenous dose, based on AUC). Also, there was an increase in stillbirths and a decrease in neonate survival starting at 0.03 mg/kg/day (0.3 times the human 5 mg dose), while the number of viable newborns and pup body weight on postnatal Day 7 were decreased at 0.1 mg/kg/day (equivalent to the human 5 mg dose). Maternal and neonatal deaths were considered related to drug-induced periparturient hypocalcemia. 8.2 Lactation Risk Summary There are no data on the presence of zoledronic acid in human milk, the effects on the breast-fed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Reclast and any potential adverse effects on the breast-fed child from Reclast, or from the underlying maternal condition. 8.3 Females and Males of Reproductive Potential Infertility There are no data available in humans. Female fertility may be impaired based on animal studies demonstrating adverse effects of Reclast on fertility parameters [see Nonclinical Toxicology (13.1)] . 8.4 Pediatric Use Reclast is not indicated for use in children. The safety and effectiveness of zoledronic acid was studied in a one-year active controlled trial of 152 pediatric subjects (74 receiving zoledronic acid). The enrolled population was subjects with severe osteogenesis imperfecta, aged 1 to 17 years, 55% male, 84% Caucasian, with a mean lumbar spine BMD of 0.431 gm/cm 2 , which is 2.7 standard deviations below the mean for age-matched controls (BMD Z-score of -2.7).

Pregnancy

8.1 Pregnancy Risk Summary Available data on the use of Reclast in pregnant women are insufficient to inform a drug-associated risk of adverse maternal or fetal outcomes. Discontinue Reclast when pregnancy is recognized. In animal reproduction studies, daily subcutaneous administration of zoledronic acid to pregnant rats during organogenesis resulted in increases in fetal skeletal, visceral, and external malformations, decreases in postimplantation survival, and decreases in viable fetuses and fetal weight starting at doses equivalent to 2 times the recommended human 5 mg intravenous dose (based on AUC). Subcutaneous administration of zoledronic acid to rabbits during organogenesis did not cause adverse fetal effects at up to 0.4 times the human 5 mg intravenous dose (based on body surface area, mg/m 2 ), but resulted in maternal mortality and abortion associated with hypocalcemia starting at doses equivalent to 0.04 times the human 5 mg intravenous dose. Subcutaneous dosing of female rats from before mating through gestation and lactation and allowed to deliver caused maternal dystocia and periparturient mortality, increases in stillbirths and neonatal deaths, and reduced pup body weight starting at doses equivalent to 0.1 times the human 5 mg intravenous dose (based on AUC) ( see Data ). Bisphosphonates are incorporated into the bone matrix, from which they are gradually released over a period of years. The amount of bisphosphonate incorporated into adult bone, and available for release into the systemic circulation is directly related to the dose and duration of bisphosphonate use. Consequently, based on the mechanism of action of bisphosphonates, there is a potential 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 the risk has not been studied. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. Data Animal Data In pregnant rats given daily subcutaneous doses of zoledronic acid of 0.1, 0.2, or 0.4 mg/kg during organogenesis, fetal skeletal, visceral, and external malformations, increases in pre-and post-implantation loss, and decreases in viable fetuses and fetal weight were observed at 0.2 and 0.4 mg/kg/day (equivalent to 2 and 4 times the human 5 mg intravenous dose, based on AUC). Adverse fetal skeletal effects at 0.4 mg/kg/day (4 times the human 5 mg dose) included unossified or incompletely ossified bones, thickened, curved or shortened bones, wavy ribs, and shortened jaw. Other adverse fetal effects at this dose included reduced lens, rudimentary cerebellum, reduction or absence of liver lobes, reduction of lung lobes, vessel dilation, cleft palate, and edema. Skeletal variations were observed in all groups starting at 0.1 mg/kg/day (1.2 times the human 5 mg dose). Signs of maternal toxicity, including reduced body weight and food consumption were observed at 0.4 mg/kg/day (4 times the human 5 mg dose). In pregnant rabbits given daily subcutaneous doses of zoledronic acid of 0.01, 0.03, or 0.1 mg/kg during gestation, no adverse fetal effects were observed up to 0.1 mg/kg/day (0.4 times the human 5 mg intravenous dose, based on body surface area, mg/m 2 ). Maternal mortality and abortion were observed in all dose groups (starting at 0.04 times the human 5 mg dose). Adverse maternal effects were associated with drug-induced hypocalcemia. In female rats given daily subcutaneous doses of 0.01, 0.03, or 0.1 mg/kg, beginning 15 days before mating and continuing through gestation, parturition and lactation, dystocia and periparturient mortality were observed in pregnant rats allowed to deliver starting at 0.01 mg/kg/day (0.1 times the human 5 mg intravenous dose, based on AUC). Also, there was an increase in stillbirths and a decrease in neonate survival starting at 0.03 mg/kg/day (0.3 times the human 5 mg dose), while the number of viable newborns and pup body weight on postnatal Day 7 were decreased at 0.1 mg/kg/day (equivalent to the human 5 mg dose). Maternal and neonatal deaths were considered related to drug-induced periparturient hypocalcemia.

Pediatric use

8.4 Pediatric Use Reclast is not indicated for use in children. The safety and effectiveness of zoledronic acid was studied in a one-year active controlled trial of 152 pediatric subjects (74 receiving zoledronic acid). The enrolled population was subjects with severe osteogenesis imperfecta, aged 1 to 17 years, 55% male, 84% Caucasian, with a mean lumbar spine BMD of 0.431 gm/cm 2 , which is 2.7 standard deviations below the mean for age-matched controls (BMD Z-score of -2.7). At one year, increases in BMD were observed in the zoledronic acid treatment group. However, changes in BMD in individual patients with severe osteogenesis imperfecta did not necessarily correlate with the risk for fracture or the incidence or severity of chronic bone pain. The adverse events observed with zoledronic acid use in children did not raise any new safety findings beyond those previously seen in adults treated for Paget’s disease of bone and treatment of osteoporosis, including ONJ and renal impairment. However, adverse reactions seen more commonly in pediatric patients included pyrexia (61%), arthralgia (26%), hypocalcemia (22%), and headache (22%). These reactions, excluding arthralgia, occurred most frequently within three days after the first infusion and became less common with repeat dosing. No cases of ONJ or renal impairment were observed in this study. Because of long-term retention in bone, Reclast should only be used in children if the potential benefit outweighs the potential risk. Plasma zoledronic acid concentration data was obtained from 10 patients with severe osteogenesis imperfecta (4 in the age group of 3 to 8 years and 6 in the age group of 9 to 17 years) infused with 0.05 mg/kg dose over 30 minutes. Mean C max and AUC (0-last) was 167 ng/mL and 220 ng.h/mL, respectively. The plasma concentration time profile of zoledronic acid in pediatric patients represent a multi-exponential decline, as observed in adult cancer patients at an approximately equivalent mg/kg dose.

Geriatric use

8.5 Geriatric Use The combined osteoporosis trials included 4863 Reclast-treated patients who were at least 65 years of age, while 2101 patients were at least 75 years old. No overall differences in efficacy or safety were observed between patients under 75 years of age with those at least 75 years of age, except that the acute phase reactions occurred less frequently in the older patients. Of the patients receiving Reclast in the osteoporosis study in men, glucocorticoid-induced osteoporosis, and Paget’s disease studies, 83, 116, and 132 patients, respectively were 65 years of age or over, while 24, 29, and 68 patients, respectively were at least 75 years of age. However, because decreased renal function occurs more commonly in the elderly, special care should be taken to monitor renal function.

Overdosage

Clinical experience with acute overdosage of zoledronic acid (Reclast) solution for intravenous infusion is limited. Patients who have received doses higher than those recommended should be carefully monitored. Overdosage may cause clinically significant renal impairment, hypocalcemia, hypophosphatemia, and hypomagnesemia. Clinically relevant reductions in serum levels of calcium, phosphorus, and magnesium should be corrected by intravenous administration of calcium gluconate, potassium or sodium phosphate, and magnesium sulfate, respectively. Single doses of Reclast should not exceed 5 mg and the duration of the intravenous infusion should be no less than 15 minutes [see Dosage and Administration ( 2 )].

Description

Reclast contains zoledronic acid, a bisphosphonic acid which is an inhibitor of osteoclastic bone resorption. Zoledronic acid is designated chemically as (1-Hydroxy-2-imidazol-1-yl-phosphonoethyl) phosphonic acid monohydrate and its structural formula is: Zoledronic acid monohydrate is a white crystalline powder. Its molecular formula is C 5 H 10 N 2 O 7 P 2
• H 2 O and a molar mass of 290.1 g/mol. Zoledronic acid monohydrate is highly soluble in 0.1N sodium hydroxide solution, sparingly soluble in water and 0.1N hydrochloric acid, and practically insoluble in organic solvents. The pH of the Reclast solution for infusion is approximately 6.0–7.0. Reclast Injection is available as a sterile solution in bottles for intravenous infusion. One bottle with 100 mL solution contains 5.330 mg of zoledronic acid monohydrate, equivalent to 5 mg zoledronic acid on an anhydrous basis. Inactive Ingredients : 4950 mg of mannitol, USP; and 30 mg of sodium citrate, USP. Zoledronic acid structural formula

Mechanism of action

12.1 Mechanism of Action Reclast is a bisphosphonate and acts primarily on bone. It is an inhibitor of osteoclast-mediated bone resorption. The selective action of bisphosphonates on bone is based on their high affinity for mineralized bone. Intravenously administered zoledronic acid rapidly partitions to bone and localizes preferentially at sites of high bone turnover. The main molecular target of zoledronic acid in the osteoclast is the enzyme farnesyl pyrophosphate synthase. The relatively long duration of action of zoledronic acid is attributable to its high binding affinity to bone mineral.

How supplied

Each bottle contains 5 mg per 100 mL NDC 66758-155-46 Handling After opening the solution, it is stable for 24 hours at 2°C to 8°C (36°F to 46°F). If refrigerated, allow the refrigerated solution to reach room temperature before administration. Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Patient information

Advise the patient to read the FDA-approved patient labeling (Medication Guide). Information for Patients Patients should be made aware that Reclast contains the same active ingredient (zoledronic acid) found in Zometa ® , and that patients being treated with Zometa should not be treated with Reclast. Reclast is contraindicated in patients with creatinine clearance less than 35 mL/min [see Contraindications ( 4 )]. Before being given Reclast, patients should tell their doctor if they have kidney problems and what medications they are taking [see Warnings and Precautions ( 5.3 )] . Reclast should not be given if the patient is pregnant or plans to become pregnant, or if she is breastfeeding [see Use in Specific Populations ( 8.1 , 8.2 , 8.3 )] . There have been reports of bronchoconstriction in aspirin-sensitive patients receiving bisphosphonates, including Reclast. Before being given Reclast, patients should tell their doctor if they are aspirin-sensitive. If the patient had surgery to remove some or all of the parathyroid glands in their neck, or had sections of their intestine removed, or are unable to take calcium supplements they should tell their doctor. Reclast is given as an infusion into a vein by a nurse or a doctor, and the infusion time must not be less than 15 minutes. On the day of treatment the patient should eat and drink normally, which includes drinking at least 2 glasses of fluid, such as water within a few hours prior to the infusion, as directed by their doctor, before receiving Reclast. After getting Reclast it is strongly recommended patients with Paget’s disease take calcium in divided doses (for example, 2 to 4 times a day) for a total of 1500 mg calcium a day to prevent low blood calcium levels. This is especially important for the two weeks after getting Reclast [see Warnings and Precautions ( 5.2 )]. Adequate calcium and vitamin D intake is important in patients with osteoporosis and the current recommended daily intake of calcium is 1200 mg and vitamin D is 800 international units to 1000 international units daily. All patients should be instructed on the importance of calcium and vitamin D supplementation in maintaining serum calcium levels. Patients should be aware of the most commonly associated side effects of therapy. Patients may experience one or more side effects that could include: fever, flu-like symptoms, myalgia, arthralgia, and headache. Most of these side effects occur within the first 3 days following the dose of Reclast. They usually resolve within 3 days of onset but may last for up to 7 to 14 days. Patients should consult their physician if they have questions or if these symptoms persist. The incidence of these symptoms decreased markedly with subsequent doses of Reclast. Administration of acetaminophen following Reclast administration may reduce the incidence of these symptoms. Physicians should inform their patients that there have been reports of persistent pain and/or a non-healing sore of the mouth or jaw, primarily in patients treated with bisphosphonates for other illnesses. During treatment with zoledronic acid, patients should be instructed to maintain good oral hygiene and undergo routine dental check-ups. If they experience any oral symptoms, they should immediately report them to their physician or dentist. Severe and occasionally incapacitating bone, joint, and/or muscle pain have been infrequently reported in patients taking bisphosphonates, including Reclast. Consider withholding future Reclast treatment if severe symptoms develop. Atypical femur fractures in patients on bisphosphonate therapy have been reported; patients with thigh or groin pain should be evaluated to rule out a femoral fracture.

Label text from the FDA structured product label by Sandoz Inc (revised Feb 3, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Zoledronic Acid in 1 product

Reclast NDC products (1)

NDC	Strength & form	Labeler	Type
66758-155	Zoledronic Acid 5 mg/100mL Injection, Solution	Sandoz Inc	NDA