![\"Zoldric\"](\"https:\/\/i0.wp.com\/www.zuviuslifesciences.in\/media\/34479\/zoledronic-acid.jpg?resize=508%2C330&ssl=1\")
[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Composition” tab_id=”1593180027679-67fc6ad4-ae7e”][vc_column_text]Zoledronic is Lyophilized Injection Each vial contains Zoledronic acid Monohydrate IP equivalent to anhydrous<\/p>\n[vc_row][vc_column][vc_tta_tour color=”peacoc” active_section=”1″][vc_tta_section title=”Description” tab_id=”1584624217032-a15849ed-97bb”][vc_column_text]Zoledronic acid contains a bisphosphonic acid which is an inhibitor of osteoclastic bone resorption. Zoledronic acid is designated chemically as (1Hydroxy-2-imidazol-1-yl-phoshoneothyl) phosphonic acid monohydrate Zoledronic acid is a white crystalline powder. Its molecular formula is C3H10N2O1P2H2O and its molecular weight is 290.1<\/p>\n
Zoledronic acid injection is available in vials as a sterile lyophilized powder or intravenous infusion. Each vials contains Zoledronic acid monohydrate equivalent to anhydrous Zoledronic acid 4 mg.<\/p>\n
Inactive Ingredients: Mannitol, IP, Trisodium Citrate dehydrate.<\/p>\n
[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Composition” tab_id=”1593180027679-67fc6ad4-ae7e”][vc_column_text]Zoledronic is Lyophilized Injection Each vial contains Zoledronic acid Monohydrate IP equivalent to anhydrous<\/p>\n
Zoledronic acid 4 mg.[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Mechanism of Action \/ Pharmcodynamics” tab_id=”1584624217050-ebb8ae5e-43a6″][vc_column_text]Clinical Pharmacology:<\/strong><\/p>\n The principal pharmacology action of Zoledronic acid is inhibition of bone reception. It is one of the most potent inhibitors of osteoclast bone resorption. Although the antiresoptive mechanism is not completely understood, several factors are thought to contribute to this action. In vitro. Zoledronic acid inhibits osteoclastic activity and and induces osteoclast apotopsis. Also blocks the osteoclastic activity and skeletal calcium release included by various stimulatory factors released by tumors. In addition to inhibiting osteoclast bone resorption, Zoledronic acid exerts direct antitumor effects on human myeloma and breast cancer cells, inhibiting their proliferation and including apotosis. Zoledronic acid is antiangiogenic in animal tumor model. This antitumor efficacy may be enhanced when used in combination with other anticancer drugs.[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Pharmacokinetics” tab_id=”1584624459062-96fb7e5b-0e23″][vc_column_text]Clinical studies in patients with hyoercalcemia of malignancy (HCM) showed that single dose infusions of Zoledronic acid are associated with decrease in serum calcium and phosphorus and increase in urinary calcium and phosphorous excretion, Normalisation of serum calcium by day 4 mg was greater for Zoledronic acid and 8 mg doses than pamidronate.<\/p>\n Hypocalcaemia of Malignancy :<\/p>\n Osteoclastic hyperactivity resulting in excessive bone resorption is the underlying pathophysiologic derangement in hypercalcamia of malignancy (HCM), tumor-induced hypercalcamia) and metastatic bone diseases. Excessive release of calcium into the blood as bone is resorbed results in polyuria and gastrointestinal disturbances, with progressive dehydration and decreasing glomerular filtration rate. This is turn results in increased renal resorption of calcium, setting up a cycle of worsening systemic hypercalcaemia. Reducing excessive bone resorption and adequate fluid administration are, therefore, essential to the management of hypocalcemia.<\/p>\n Clinical Pharmacokinetics<\/strong><\/p>\n Single or multiple (q 28 days) 5 minute infusion or 2, 48, or 16mg Zoledronic acid were given to patients with cancer and bone metastases. The post infusion decline of Zoledronic acid concentrations in plasma was consistent with a triphasic process showing a rapid decrease from peak concentrations at end-of-infusion to <1% C max hours and t \u00bd\u00a0 beta 1.87 hours for the early disposition phases of the drug. The terminal elimination phase of Zoledronic acid was 146 hours. There are under the plasma concentration versus time curve (AUCO-24h) of Zoledronic acid measured over three cycles was low, with mean AUCO-24h rations for cycles 2 and 3 versus 1 of 1.13 + 0.30 and 1.16 + 0.36, respectively.<\/p>\n In vitro and ex vivo studies showed low affinity of Zoledronic acid for the cellular, components of human blood, binding to human plasma proteins was approximately 22% and was independent of the concentration of Zoledronic acid.<\/p>\n Metabolism:<\/strong><\/p>\n Zoledronic acid does not inhibit human P450 enzymes in vitro, Zoledronic acid dose not undergo biotransformation in vivo In animal studies <3% of the administered intravenous does was found in the feces, with the balance either recovered in the urine or taken up by bone, indication that the drug is eliminated intact via the kidney.<\/p>\n Excretion:<\/strong><\/p>\n In patients with cancer and bone metastases on average (\u00b1s.d.) 39\u00b116% of the administration Zoledronic acid dose was recovered in the urine within 24 hours, with only trace amounts of drug found in urine post day 2. The cumulative percent of drug excreted in the urine over 0-24 hours was independent of dose. The balance of drug not recovered in urine over 0.-24 hours, representing drug presumably bound to bone is slowly released back into the systemic circulation, giving rise to the observed prolonged low plasma concentrations days 2 to 20 post dose. The 0-24 hours renal clearance 3.7 + 2.0L\/h.<\/p>\n Zoledronic acid clearance was reasonably independent of dose and demographic variables, with effect of bodyweight gender and race, on clearance was dependent or creatinine clearance.<\/p>\n Special Populations:<\/strong><\/p>\n No pharmacokinetics data in patients with hypercalcemia.<\/p>\n Pediatrics:<\/strong>\u00a0No pharmacokinetics data in pediatric patients.<\/p>\n Geratrics:<\/strong>\u00a0the pharmacokinetics of Zoledronic acid were not affected by age in patients with cancer and bone metastases aged 38 years to 84 years.<\/p>\n Race:\u00a0<\/strong>The pharmacokinetics of Zoledronic acid were not affected by race in patients with cancer and bone metastases.<\/p>\n Hepatic Insufficiency:\u00a0<\/strong>There are no pharmacokinetic data in patients with impaired<\/p>\n liver functions :<\/strong>\u00a0Zoledronic acid is not cleared by liver therefore impaired liver function mayno affect the pharmacokinetic of Zoledronic acid.<\/p>\n Renal Insufficiency:<\/strong>\u00a0Patients with mild to moderate (creatinine 50-80 ml \/ min) renal impairment showed an increase in plasma AUC of 26-27 % whereas patients with moderate to severe renal impairment (creatinine clearance 30-50ml\/min) showed an increase I plasma AUC 27-41% Limited pharmacokinetic data are available for Zoledronic acid in patients with severe renal impairment (creatinine clearance <30 ml\/min). Based on population PK\/PD modeling the risk of renal deterioration appears to increase with AUC which is doubled at a creatinine clearance of 10 ml\/min.[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Indications” tab_id=”1584624839401-59481bbb-bdc7″][vc_column_text]Hypercalcemia of Malignany<\/p>\n Zoldric (Zoledronic acid) injection is indicated for the treatment of hypercalcaemia of; malignancy following adequate saline rehydration.<\/p>\n Vigorous saline hydration, and integral part of hypercalcemia therapy, should be intiated promptly and an attempt should be made to restore the urine output to about 2 L\/throughful treatment.<\/p>\n The safety and efficacy of Zoledronic acid in the treatment of hypercalcamia associated<\/p>\n with hyperparathyroidism or with other non-tumor-related conditions have not been established.[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Dosage & Administration” tab_id=”1584625017135-3ffdd9c5-1bd6″][vc_column_text]Hypercalcaemia of Malignancy<\/strong><\/p>\n The recommended dose of Zoledronic acid in hypercalcaemia (albumin corrected serum calcium \u2013 12mg\/dl) is 4 mg. The 4 mg is given as a single dose i.v. infusion over 15 minutes. Patients should be adequately rehydrated prior to administration of Zoledronic acid. Retreatment with Zoledronic acid 4mg, may be considered it serum calcium does no return to normal or remain normal after initial treatment. It is recommended that a minimum of 7 days elapse before retreatment, to allow for full response to the initial dose.<\/p>\n Preparation of Solution:<\/strong><\/p>\n Zoledronic Lyophilized powder of infusion is reconstituted by adding 5ml of sterile water for injection to each vial. The resulting concentration allows for withdrawal. The content of the reconstituted vials are withdrawn and further diluted in 100ml of sterile 0.9% sodium chloride or 5% Dextrose injection. Do not store undiluted concentrate in a syringe, to avoid inadvertent injection. The dose must be given as a single intravenous solution infusion over no less than than 15 minutes.<\/p>\n If not used immediately after dilution with infusion media, for microbiological integrity the solution should be refrigerated at 2\u00b0C-8\u00b0 (36\u00b0 F- 46\u00b0 F). Zoledronic acid must not be mixed with calcium \u2013 containing infusion solutions such as Lactated Ringers Solution, and should administered as a single intravenous solution in a line separate from all other drugs.[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Warnings” tab_id=”1587978464677-818e3c8a-8b36″][vc_column_text]<\/p>\n [\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Precautions” tab_id=”1587978466341-e08f7517-4cca”][vc_column_text]<\/p>\n [\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Adverse Reactions (Side Effects)” tab_id=”1587978467943-190d6254-3b32″][vc_column_text]Hypocalcaemia of malignancy<\/p>\n Adverse reactions to Zoledronic acid injection are usually mild an transient and similar to those reported for other bisphosphonates. Intravenous administration has been most commonly associated with fever. Occasionally patients experience a flu like syndrome consisting of fever, chills, bone pain and\/prarthralgias, and myalgias. Gastrointestinal reactions such as nausea and vomiting have been reported following intravenous infusion of Zoledronic acid. Local reactions at the infusion site, such as redness or swelling, were observed infrequently. In most cases, no specific treatment is required and symptoms subside after 24-28 hours.<\/p>\n Rare cases of rash, pruritus and chest pain have been reported following treatment with Zoledronic acid. As with other bisphonates, cases of conjusctivies and hypomagnesemia have been reported following treatment with Zoledronic acid.<\/p>\n Body as a Whole : Asthenia, Chest Pain, leg edema, mucositis, metastases<\/p>\n Digestive System :Dysphapia<\/p>\n Hemic and Lymphic System: Granulocytopenia, Thrombocytopenia, pancytopenia<\/p>\n Infection : non-specific infection<\/p>\n Laboratory Abnormalities: Hypocalcaemia<\/p>\n Metabolic and Nutritional : Dehydration<\/p>\n Musculoskeletal :Arthralgias<\/p>\n Nervous System : Headache, somnolence<\/p>\n Respiratory System: Pleural effusion.<\/p>\n Adverse events are listed regardless of presumed causality to study drug, among the less frequently occurring adverse events (<15% of patients), rigors, hypokalemia, influenza, like illness and hypocalcaemia showed a trend for more events with bisphosphonate administration compared to place bo group.<\/p>\n Less common adverse events reported more often with Zoledronic acid 4 mg than pamidronate included decreased weight, which was reported in 13.0% of patients in the Zoledronic acid 4mg compared with 7.1% in the pamidronate group. The incidence of decreased weight, however was similar for the place bo group (12.5%) and Zoledronic acid, Decreased appetite was reported in slightly are patients in the Zoledronic acid 4mg (10.08%) compared with pamidornate (7.3%) and placebo (8.6%) groups, but the clinical significance or these small differences are not clear.<\/p>\n Single doses of Zoledronic acid should not exceed 4mg and the duration of the intravenous infusion should be no less then 15 minutes.[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Drug Interactions” tab_id=”1587978788920-a652582e-1377″][vc_column_text]No clinically apparent interactions occurred when Zoledronic acid was administered concomitantly with commonly used anticancer drugs, diuretics antibiotics and analgesics, Zoledronic acid shows no apperaciable binding in vitro to plasma protein and a human P450 enzymes, indicating a low likelihood of pharmackinetic drug interactions, However, no formal clinical interactions studies have been performed.<\/p>\n Caution is advised when biophosphonates are administered with amino glycoside, since these agents may have a additive effect to lower serum calcium level of prolonged periods. This has not been reported in Zoledronic acid clinical trials. Caution is adviseed when Zoledronic acid is used with potentially nephrotoxic drugs. (Renal functions be monitored) in multiple myeloma patients the risk of renal daysfunction may be increased when Zoledronic acid used in combination with thaldio<\/p>\n CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY<\/p>\n Carcinogenesis : Zoledronic acid was administered orally (gavage) to rats and mice for a least 104 weeks without evidence of carcinogenic potential. Chronic parenteral administration was not feasible given the potential of the compound to cause serve loyal irritation.<\/p>\n Mutagenesis : Zoledronic acid was not genotoxic in the Ames bacterial mutagenicity assay, in the Chinese hamster over cell assay, or in the Chinese hamster gene mutation assay, with or without metabolic activation. Zoledronic acid was not genotoxic in the vivo rat micronucleus assay.<\/p>\n Impairment of Fertility : Female rats were given subcutaneous doses of Zoledronic acid of 0.01,0.03 or 01 mg \/ kg \/ day beginning of 15 days before mating and continuing through gestation Effects observed in the high-dose group (with systemic exposure of 1.2 time the human systemic exposure following an intravenous dose of 4 mg, based AUC comparision) included inhibition if ovulation and a decrease in the number of pregnant rats.<\/p>\n Pregnancy : Category D. There is no clinical evidence to support the use of Zoledronic acid in pregnant women Therefore, Zoledronic acid should no be administered during pregnancy except for life threating hypocalcaemia.<\/p>\n NURSING MOTHERS :<\/strong><\/p>\n It is not known whether Zoledronic acid is excreted in human milk. Because many drugs are excreted in human milk, and Zoledronic acid binds to bone, it should be administered to a nursing woman.<\/p>\n PredatricUse :<\/strong><\/p>\n The safely and effectiveness of Zoledronic acid in pediatric patients have not been established. Because of long term retention in bone. Zoledronic acid should only be used in children if the potential risk.<\/p>\n Geriatric Use :<\/strong><\/p>\n No significant differences in response rate of adverse reactions were seen in geriatric patients receiving Zoledronic acid as compared to younger patients.[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Overdose & Contradiction” tab_id=”1587978790937-0b0c9a9f-418f”][vc_column_text]There is no experience of acute overdose with Zoledronic acid. Two patients received Zoledronic acid 32mg over 5 minutes in clinical trials. Neither patient experienced any clinical or laboratory toxicity, Over dosage may cause clinically significant hypocalcaemia, hypophoshatemia, and hypomagnesaemia. 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, repectively.<\/p>\n CONTRAINDICATIONS :<\/strong><\/p>\n Zoledronic acid injection is contraindicated in patients with clinically significant<\/p>\n hypersenstivity to Zoledronic acid or other bisphosphonates or any of the excipients[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Storage” tab_id=”1587978793604-7c71901c-62cf”][vc_column_text]Store Below 30\u00b0C[\/vc_column_text][\/vc_tta_section][vc_tta_section title=”Presentation” tab_id=”1587978938510-bff2f998-3197″][vc_column_text]Each vial of Zoledronic contains Zoledronic acid monohydrate equivalent to anhydrous Zoledronic acid 4mg.<\/p>\n Inactive Ingredients: Mannitol, IP, Trisodium citrate dehydrate.<\/p>\n Carton of 1 vial.[\/vc_column_text][\/vc_tta_section][\/vc_tta_tour][\/vc_column][\/vc_row]<\/p>\n","protected":false},"excerpt":{"rendered":"\n
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