ZOLEDRONIC ACID- zoledronic acid injection, solution

Land: Verenigde Staten

Taal: Engels

Bron: NLM (National Library of Medicine)

Werkstoffen:

ZOLEDRONIC ACID (UNII: 6XC1PAD3KF) (ZOLEDRONIC ACID ANHYDROUS - UNII:70HZ18PH24)

Beschikbaar vanaf:

Dr.Reddy's Laboratories Ltd

INN (Algemene Internationale Benaming):

ZOLEDRONIC ACID

Samenstelling:

ZOLEDRONIC ACID ANHYDROUS 5 mg in 100 mL

Toedieningsweg:

INTRAVENOUS

Prescription-type:

PRESCRIPTION DRUG

therapeutische indicaties:

Zoledronic acid injection 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) ]. Zoledronic acid injection 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 zoledronic acid injection. Hypersensitivity reactions including urticaria, angioedema, and anaphylactic reaction/shock have been reported [see Adverse Reactions (6.2) ] . Risk Summary Available data on the use of zoledronic acid in pregnant women are insufficient to inform a drug-associated risk of adverse maternal or fetal outcomes. Discontinue zoledronic acid 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/m2 ), 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 to 4% and 15 to 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/m2 ). 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. Risk Summary There are no data on the presence of zoledronic acid in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for zoledronic acid and any potential adverse effects on the breast-fed child from zoledronic acid or from the underlying maternal condition. Infertility There are no data available in humans. Female fertility may be impaired based on animal studies demonstrating adverse effects of zoledronic acid on fertility parameters [see Nonclinical Toxicology (13.1)]. Zoledronic acid injection 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/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 including osteonecrosis of the jaw (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, zoledronic acid injection 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 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. Of the patients receiving zoledronic acid injection in the Paget’s disease studies, 132 patients, were 65 years of age or over, while 68 patients, were at least 75 years of age. Because decreased renal function occurs more commonly in the elderly, special care should be taken to monitor renal function. Zoledronic acid injection is contraindicated in patients with creatinine clearance less than 35 mL/min and in those with evidence of acute renal impairment. There are no safety or efficacy data to support the adjustment of the zoledronic acid injection dose based on baseline renal function. Therefore, no dosage adjustment is required in patients with a creatinine clearance of greater than or equal to 35 mL/min [see Warnings and Precautions (5.3) , Clinical Pharmacology (12.3) ]. Risk of acute renal failure may increase with underlying renal disease and dehydration secondary to fever, sepsis, gastrointestinal losses, diuretic therapy, advanced age, etc. [see Adverse Reactions (6.2) ]. Zoledronic acid injection is not metabolized in the liver. No clinical data are available for use of zoledronic acid injection in patients with hepatic impairment.

Product samenvatting:

Each bottle contains 5 mg per 100 mL:                     NDC 55111-688 -52 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); [see USP Controlled Room Temperature].   Single dose vial.

Autorisatie-status:

Abbreviated New Drug Application

Bijsluiter

ZOLEDRONIC ACID- ZOLEDRONIC ACID INJECTION, SOLUTION
Dr.Reddy's Laboratories Ltd
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MEDICATION GUIDE
Zoledronic acid Injection
(ZOE-le-DRON-ik AS-id)
Read the Medication Guide that comes with zoledronic acid injection
before you start taking it and each
time you get a refill. There may be new information. This Medication
Guide does not take the place of
talking with your doctor about your medical condition or treatment.
Talk to your doctor if you have any
questions about zoledronic acid injection.
What is the most important information I should know about Zoledronic
acid injection?
You should not receive zoledronic acid injection if you are already
receiving Zometa. Both zoledronic
acid injection and Zometa contain zoledronic acid.
Zoledronic acid injection can cause serious side effects including:
1. Low calcium levels in your blood (hypocalcemia)
2. Severe kidney problems
3. Severe jaw bone problems (osteonecrosis)
4. Unusual thigh bone fractures
5. Bone, joint or muscle pain
1. Low calcium levels in your blood (hypocalcemia).
Zoledronic acid injection may lower the calcium levels in your blood.
If you have low blood calcium
before you start taking zoledronic acid injection, it may get worse
during treatment. Your low blood
calcium must be treated before you take zoledronic acid injection.
Most people with low blood calcium
levels do not have symptoms, but some people may have symptoms. Call
your doctor right away if you
have symptoms of low blood calcium such as:
• Spasms, twitches, or cramps in your muscles
• Numbness or tingling in your fingers, toes, or around your mouth
Your doctor may prescribe calcium and vitamin D to help prevent low
calcium levels in your blood, while
you take zoledronic acid injection. Take calcium and vitamin D as your
doctor tells you to.
2. Severe kidney problems.
Severe kidney problems may happen when you take zoledronic acid
injection. Severe kidney problems
may lead to hospitalization or kidney dialysis and can be
life-threatening. Your risk of kidney problems is
hig

Productkenmerken

ZOLEDRONIC ACID- ZOLEDRONIC ACID INJECTION, SOLUTION
DR.REDDY'S LABORATORIES LTD
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
ZOLEDRONIC ACID
INJECTION SAFELY AND EFFECTIVELY.
SEE FULL PRESCRIBING INFORMATION FOR ZOLEDRONIC ACID INJECTION.
ZOLEDRONIC ACID INJECTION, FOR INTRAVENOUS INFUSION
INITIAL U.S. APPROVAL: 2001
INDICATIONS AND USAGE
Zoledronic acid injection is a bisphosphonate indicated for:
Treatment of Paget’s disease of bone in men and women (1.5)
DOSAGE AND ADMINISTRATION
Infusion given intravenously over no less than 15 minutes:
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)
DOSAGE FORMS AND STRENGTHS
5 mg in a 100 mL ready-to-infuse solution (3)
CONTRAINDICATIONS
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 zoledronic acid injection (4,
6.2)
WARNINGS AND PRECAUTIONS
_Products Containing Same Active Ingredient_: Patients receiving
Zometa should not receive zoledronic
acid injection (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 Femur Fractures_ have been reported. Patients with thigh or
groin pain should be evaluated to
rule out a femoral fracture (5.5).
_Severe Bone, Joint, and Muscle Pain _may occur. Withhold future doses
of zoledronic acid injection if