Included as part of the PRECAUTIONS section.

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.

Hypocalcemia and Mineral Metabolism

Pre-existing 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 ].

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, ADVERSE REACTIONS, INFORMATION FOR PATIENTS].

All osteoporosis patients should be instructed on the importance of calcium and vitamin D supplementation in maintaining serum calcium levels [see DOSAGE AND ADMINISTRATION, ADVERSE REACTIONS, INFORMATION FOR PATIENTS].

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].

Reclast is not recommended for use in patients with severe renal impairment (creatinine clearance < 35 mL/min) due to lack of adequate clinical experience in this population [see ADVERSE REACTIONS].

To help prevent renal impairment, patients especially those receiving diuretic therapy, should be appropriately hydrated prior to administration of Reclast. Reclast should be used with caution with other nephrotoxic drugs [see DRUG INTERACTIONS].

Renal impairment has been observed following the administration of zoledronic acid, especially in patients with pre-existing renal compromise or additional risk factors (e.g., oncology patients with chemotherapy, concomitant nephrotoxic medications, severe dehydration, etc), the majority of whom received a 4 mg dose every 3-4 weeks, but it has been observed in patients after a single administration.

Monitor serum creatinine before each Reclast dose. Transient increase in serum creatinine may be greater in patients with impaired renal function; consider interim monitoring of serum creatinine in at-risk patients.

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, corticosteroids, poor oral hygiene).

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. The clinical judgment of the treating physician should guide the management plan of each patient based on individual benefit/risk assessment [see ADVERSE REACTIONS].

Pregnancy

RECLAST SHOULD NOT BE USED DURING PREGNANCY. Reclast may cause fetal harm when administered to a pregnant woman. If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while on Reclast therapy [see Use in Specific Populations].

Musculoskeletal Pain

In post-marketing experience, severe and occasionally incapacitating bone, joint, and/or muscle pain have been infrequently reported in patients taking bisphosphonates, including Reclast. The time to onset of symptoms varied from one day to several months after starting the drug. Consider withholding future Reclast treatment if severe symptoms develop. Most patients had relief of symptoms after stopping. A subset had recurrence of symptoms when rechallenged with the same drug or another bisphosphonate [see ADVERSE REACTIONS].

Patients with Asthma

While not observed in clinical trials with Reclast, there have been reports of bronchoconstriction in aspirin-sensitive patients receiving bisphosphonates. Use Reclast with caution in aspirin-sensitive patients.

Patient Counseling Information

See FDA-Approved Patient Labeling .

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.

Before being given Reclast patients should tell their doctor if they have kidney problems and what medications they are taking.

Reclast should not be given if the patient is pregnant or plans to become pregnant, or if she is breast-feeding [see WARNINGS and PRECAUTIONS].

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].

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 800 IU - 1000 IU 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 or ibuprofen following Reclast administration may reduce the incidence of these symptoms.

Physicians should inform their patients there have been reports, primarily in patients treated with bisphosphonates for other illnesses, of persistent pain and/or a non-healing sore of the mouth or jaw, and if they experience these symptoms to tell their physician or dentist.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis: Standard lifetime carcinogenicity bioassays were conducted in mice and rats. Mice were given daily oral doses of zoledronic acid of 0.1, 0.5, or 2.0 mg/kg/day. There was an increased incidence of Harderian gland adenomas in males and females in all treatment groups (at doses ≥ 0.002 times the human intravenous dose of 5 mg, based on mg/m² comparison). Rats were given daily oral doses of zoledronic acid of 0.1, 0.5, or 2.0 mg/kg/day. No increased incidence of tumors was observed (at doses ≤ 0.1 times the human intravenous dose of 5 mg, based on mg/m²comparison).

Mutagenesis: Zoledronic acid was not genotoxic in the Ames bacterial mutagenicity assay, in the Chinese hamster ovary cell assay, or in the Chinese hamster gene mutation assay, with or without metabolic activation. Zoledronic acid was not genotoxic in the in vivo rat micronucleus assay.

Impairment of Fertility: Female rats were given daily subcutaneous doses of zoledronic acid of 0.01, 0.03, or 0.1 mg/kg beginning 15 days before mating and continuing through gestation. Effects observed in the high-dose group (equivalent to human systemic exposure following a 5 mg intravenous dose, based on AUC comparison) included inhibition of ovulation and a decrease in the number of pregnant rats. Effects observed in both the mid-dose group and high-dose group (0.3 to 1 times human systemic exposure following a 5 mg intravenous dose, based on AUC comparison) included an increase in pre-implantation losses and a decrease in the number of implantations and live fetuses.

Use In Specific Populations

Pregnancy

Pregnancy Category D [see WARNINGS and PRECAUTIONS].

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 space, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on this risk has not been established.

In female rats given subcutaneous doses of zoledronic acid of 0.01, 0.03, or 0.1 mg/kg/day beginning 15 days before mating and continuing through gestation, the number of stillbirths was increased and survival of neonates was decreased in the mid- and high-dose groups ( ≥ 0.3 times the anticipated human systemic exposure following a 5 mg intravenous dose, based on an AUC comparison). Adverse maternal effects were observed in all dose groups ( ≥ 0.1 times the human systemic exposure following a 5 mg intravenous dose, based on an AUC comparison) and included dystocia and periparturient mortality in pregnant rats allowed to deliver. Maternal mortality was considered related to drug-induced inhibition of skeletal calcium mobilization, resulting in periparturient hypocalcemia. This appears to be a bisphosphonate class effect.

In pregnant rats given daily subcutaneous dose of zoledronic acid of 0.1, 0.2, or 0.4 mg/kg during gestation, adverse fetal effects were observed in the mid- and high-dose groups (about 2 and 4 times human systemic exposure following a 5 mg intravenous dose, based on AUC comparison). These adverse effects included increases in pre- and post-implantation losses, decreases in viable fetuses, and fetal skeletal, visceral, and external malformations. Fetal skeletal effects observed in the high-dose group included unossified or incompletely ossified bones, thickened, curved or shortened bones, wavy ribs, and shortened jaw. Other adverse fetal effects observed in the high-dose group included reduced lens, rudimentary cerebellum, reduction or absence of liver lobes, reduction of lung lobes, vessel dilation, cleft palate, and edema. Skeletal variations were also observed in the low-dose group (about 1.2 times the anticipated human systemic exposure, based on an AUC comparison). Signs of maternal toxicity were observed in the high-dose group and included reduced body weights and food consumption, indicating that maximal exposure levels were achieved in this study.

In pregnant rabbits given subcutaneous doses of zoledronic acid of 0.01, 0.03, or 0.1 mg/kg/day during gestation (at doses ≤ 0.4 times the anticipated human systemic exposure following a 5 mg intravenous dose, based on mg/m² comparison) no adverse fetal effects were observed. Maternal mortality and abortion occurred in all treatment groups (at doses ≥ 0.04 times the human 5 mg intravenous dose, based on mg/m² comparison). Adverse maternal effects were associated with, and may have been caused by, drug-induced hypocalcemia [see WARNINGS and PRECAUTIONS].

RECLAST SHOULD NOT BE USED DURING PREGNANCY. If the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving Reclast [see WARNINGS and PRECAUTIONS].

Nursing Mothers

It is not known whether Reclast is excreted in human milk. Because many drugs are excreted in human milk, and because Reclast binds to bone long-term, Reclast should not be administered to a nursing woman.

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 1-17 years, 55% male, 84% Caucasian, with a mean lumbar spine BMD of 0.431 gm/cm², 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. 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. 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 3-8 years and 6 in the age group of 9-17 years) infused with 0.05 mg/kg dose over 30 minutes. Mean Cmax 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

The combined osteoporosis trials included 4761 Reclast-treated patients who were at least 65 years of age, while 2083 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.

However, because decreased renal function occurs more commonly in the elderly, special care should be taken to monitor renal function.

Phase 3 studies of Reclast in the treatment of Paget's disease of bone included 132 Reclast-treated patients who were at least 65 years of age, while 68 Reclast-treated patients were at least 75 years old. No overall differences in efficacy or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Renal Impairment

Reclast is not recommended for patients with severe renal impairment (creatinine clearance < 35 mL/min) due to lack of adequate clinical experience in this population. No dosage adjustment is required in patients with a creatinine clearance of 35 mL/min [see WARNINGS and PRECAUTIONS, CLINICAL PHARMACOLOGY].

Hepatic Impairment

Reclast is not metabolized in the liver. No clinical data are available for use of Reclast in patients with hepatic impairment.

Bookmark this page: