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ZOLEDRONIC ACID CONCENTRATE is a brand name for Zoledronic Acid, supplied as a solution. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: AND CLINICAL USE ................................................................................... 3 CONTRAINDICATIONS ..................................................................................................... 3 WARNINGS AND…
Verbatim from this product's HC label. Tap a section to expand.
Adverse Drug Reaction Overview The most serious adverse drug reactions reported in patients receiving zoledronic acid for injection are: anaphylactic reaction, ocular adverse events, osteonecrosis of the jaw, atypical femoral fracture, atrial fibrillation, renal function deterioration, acute phase reaction, and hypocalcaemia.
Adverse reactions to zoledronic acid for injection are usually mild and transient and similar to those reported for other bisphosphonates. Intravenous administration has been most commonly associated with fever. Within three days after zoledronic acid for injection admin istration, an acute phase reaction has been reported commonly, with symptoms including pyrexia, fatigue, bone pain and/or arthralgias, myalgias, chills, influenza-like illness, arthritis and joint swelling; these symptoms usually resolve within a few days.
Gastrointestinal reactions such as nausea and vomiting have been reported commonly following intravenous infusion of zoledronic acid for injection. Local reactions at the infusion site, such as redness or swelling and/or pain, were observed infrequently.
Rash or pruritis and chest pain have been reported uncommonly following treatment with zoledronic acid for injection. As with other bisphosphonates, isolated cases of hypomagnesaemia have been reported. Isolated cases of episcleritis have been reported, uveitis has been reported rarely, blurred vision has been reported uncommonly and cases of conjunctivitis have been reported commonly.
Cardiac arrhythmias associated with hypocalcaemia have been reported rarely following treatment with zoledronic acid for injection. Atrial fibrillation not associated with hypocalcaemia has been reported following treatment with zoledronic acid.
Cases of interstitial lung disease have been reported rarely following treatment with zoledronic acid for injection. Clinical Trial Adverse Drug Reactions Tumour-Induced Hypercalcaemia Clinical Trials Patients with tumour-induced hypercalcaemia may have numerous confounding medical conditions that make causality of adverse events difficult to assess due to the prevalence and wide variety of symptoms related to the underlying disease, its progression and the side effects of cytotoxic chemotherapy.
In patients treated with Zoledronic Acid Concentrate, serum calcium may fall to asymptomatic hypocalcaemic levels. This frequently leads to a reduction in renal calcium excretion which is accompanied by a fall in serum phosphate levels that does not require treatment.
Serious Warnings and Precautions Osteonecrosis of the jaw (ONJ), (See Musculoskeletal, Osteonecrosis of the Jaw below) Deterioration in renal function (See Renal below) The use of Zoledronic Acid Concentrate is not recommended in patients with severe renal impairment (See Special Populations below) Hypocalcaemia (See General, Hypocalcaemia below) Single doses of Zoledronic Acid Concentrate should not exceed 4 mg and the duration of the infusion should be no less than 15 minutes.
(See Renal and DOSAGE AND ADMINISTRATION below) General Drug Interactions Zoledronic Acid Concentrate contains the same active ingredient that is contained in ACLASTA® (zoledronic acid, 5 mg/100 mL). Patients being treated with Zoledronic Acid Concentrate should not be treated with other drugs containing zoledronic acid concomitantly.
Zoledronic Acid Concentrate should not be given together with other bisphosphonates since the combined effects of these agents are unknown. Zoledronic acid for injection is eliminated by renal excretion. g. g. diuretics, ACE inhibitors, leading to dehydration).
Caution is advised when Zoledronic Acid Concentrate is administered with anti-angiogenic drugs, as the incidence of ONJ is increased when these drugs are used concomitantly (see Osteonecrosis of the Jaw, DRUG INTERACTIONS, Drug-Drug Interactions).
Caution is advised when Zoledronic Acid Concentrate is administered with loop diuretics (particularly in patients treated for TIH), with aminoglycosides, or with calcitonin, since there may be an additive effect on the risk of developing hypocalcaemia.
Zoledronic Acid Concentrate should be used with extreme caution in conjunction with other antineoplastic agents that are known to produce renal dysfunction (it is advised that renal function be monitored) or where the dose depends upon renal function (for example platinum-containing agents).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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0% of patients receiving zoledronic acid for injection 4 mg and pamidronate 90 mg, respectively, in the clinical trials in tumour-induced hypercalcaemia. 0% in patients receiving zoledronic acid for injection 4 mg and pamidronate 90 mg, respectively.
Table 1 lists the adverse events considered to be treatment-related in the tumour-induced hypercalcaemia trials. 2 0 Bone Metastases of Solid Tumours and Osteolytic Lesions of Multiple Myeloma Clinical Trials The adverse event data pertaining to bone metastases of solid tumours and osteolytic lesions of multiple myeloma are based upon the core and extension phases of the three pivotal controlled trials in this indication (see DETAILED PHARMACOLOGY and CLINICAL STUDIES).
These trials included 2042 safety evaluable patients treated with either zoledronic acid for injection 4 mg, pamidronate 90 mg, or placebo. Of these 2042 patients who entered the core phase of the trials, 969 completed the core phase, 619 entered the safety extension phase, and 347 completed the extension phase.
8 months for patients with breast cancer and multiple myeloma, and 4 months for pa tients with lung cancer and other solid tumours. 7 months for patients with lung cancer and other solid tumours (see CLINICAL STUDIES). In general, zoledronic acid for injection was well tolerated across all studies for various tumour types in patients with bone metastases and in patients with multiple myeloma.
The proportion of patients experiencing Grade 3 and Grade 4 laboratory abnormalities and adverse events were similar in patients treated with zoledronic acid for injection and pamidronate. 7% of patients receiving zoledronic acid for injection 4 mg, pamidronate 90 mg and placebo, respectively.
4% and 0% of patients receiving zoledronic acid for injection 4 mg, pamidronate 90 mg and placebo, respectively. The most commonly reported (>15%) adverse events occurred with similar frequencies in the zoledronic acid for injection, pamidronate and placebo treatment groups, and most of these events may have been related to the underlying disease state or cancer therapy.
Table 2 lists the events which occurred in ≥ 15% of patients regardless of study drug relationship by preferred term and treatment group, in the bone metastases trials.
Table 2:
Commonly Reported Events in Three Bone […]
Zoledronic Acid Concentrate should not be mixed with calcium-containing intravenous infusions. Effects on ability to drive or use machines In rare cases, somnolence and/or dizziness may occur, in which case the patient should not drive, operate potentially dangerous machinery or engage in other activities that may be hazardous.
Page 5 of 51 Hypocalcaemia Hypocalcaemia has been reported in patients treated with zoledronic acid for injection. QTc prolongation and neurologic adverse events (tonic-clonic seizures, tetany and numbness) have been reported secondary to cases of severe hypocalcaemia.
In some instances, the hypocalcaemia required hospitalization and/or was life-threatening. Caution is advised when Zoledronic Acid Concentrate is administered with other hypocalcaemia-causing drugs (including aminoglycosides, calcitonin, or loop diuretics), as they may have an additive effect resulting in severe hypocalcaemia (see also DRUG INTERACTIONS).
Patients who have undergone thyroid surgery may be particularly susceptible to develop hypocalcaemia due to relative hypoparathyroidism. Serum albumin-corrected calcium should be measured prior to each dose and during therapy with Zoledronic Acid Concentrate (see Monitoring and Laboratory Tests).
Zoledronic Acid Concentrate is contraindicated in patients who have non-corrected hypocalcaemia at the time of infusion (see CONTRAINDICATIONS). Tumour-Induced Hypercalcaemia It is essential in the initial treatment of tumour-induced hypercalcaemia that intravenous rehydration be instituted to restore urine output.
All patients, including patients with mild to moderate renal impairment, should be hydrated adequately throughout treatment, but overhydration must be avoided. In patients with cardiac disease, especially in the elderly, additional saline overload may precipitate cardiac failure (left ventricular failure or congestive heart failure).
Fever (influenza - like symptoms) may also contribute to this deterioration. Carcinogenesis and Mutagenesis In carcinogenicity studies, zoledronic acid was administered orally (gavage) to rats and mice for at least 104 weeks without evidence of carcinogenic potential.
Chronic parenteral administration was not feasible given the potential of the compound to cause severe local irritation. The pharmacological bone changes (nonproliferative hyperostosis) typically observed following long term bisphosphonate administration to young animals with growing skeletons gave clear evidence of systemic exposure to zoledronic acid in both species at all doses.
Six mutagenicity studies were conducted with zoledronic acid: three Ames Assays (using E. coli and/or S. typhimurium), a gene mutation assay using V79 hamster cells, a cytogenetics test with Chinese hamster cells and an in vivo micronucleus assay in rats.
There was no evidence of mutagenic potential. Cardiovascular In a 3-year, randomized, double-blind controlled trial that evaluated the efficacy and safety of zoledronic acid 5 mg dose once yearly vs. 9% (75 out of 3,852) in patients receiving zoledronic acid 5 mg and placebo, respectively.
6% (22 out of 3,852) in patients receiving zoledronic acid 5 mg and placebo, respectively. The imbalance observed in this trial has not been observed in other trials with zoledronic acid, including those with zoledronic acid for injection 4 mg administered every 3 to 4 weeks in oncology patients.
The mechanism behind the increased incidence of atrial fibrillation in this sin gle clinical trial is unknown. Hepatic/Biliary/Pancreatic Hepatic Impairment As only limited clinical data are available for patients with […]