Zoledronate
Zoledronate Uses, Dosage, Side Effects, Food Interaction and all others data.
Zoledronate belongs to the class of nitrogen-containing bisphosphonates and acts primarily on bone. It is an inhibitor of osteoclast-mediated bone resorption. The action of bisphosphonates on bone is based on their high affinity for mineralized bone. Intravenously administered Zoledronate is rapidly distributed to bone. The main molecular target of Zoledronate in the osteoclast is the enzyme farnesyl pyrophosphate synthase, but this does not exclude other mechanisms. Clinical studies in tumour-induced hypercalcemia demonstrated that the effect of Zoledronate is characterized by decreases in serum calcium and urinary calcium excretion. In addition to its inhibitory activity against bone resorption, Zoledronate also possesses anti-tumour activity, anti-angiogenic activity, anti-pain activity, cytostatic and pro-apoptotic activity on tumour cells and synergistic cytostatic effect with other anti-cancer drugs. There was no accumulation of the active substance in plasma after multiple doses given every 28 days. Zoledronate is not metabolized and is excreted unchanged via the kidney.
Zoledronate is a third generation, nitrogen containing bisphosphonate that inhibits osteoclast function and prevents bone resorption. The therapeutic window is wide as patients are unlikely to suffer severe effects from overdoses and the duration of action is long. Patients should be counselled regarding the risk of electrolyte deficiencies, renal impairment, osteonecrosis of the jaw, atypical femoral fractures, bronchoconstriction, hepatic impairment, hypocalcemia, and embryo-fetal toxicity.
| Trade Name | Zoledronate |
| Generic | Zoledronic acid |
| Zoledronic acid Other Names | ácido zoledrónico, Zoledronate, Zoledronic acid |
| Type | |
| Formula | C5H10N2O7P2 |
| Weight | Average: 272.0896 Monoisotopic: 271.996323708 |
| Protein binding | Zoledronic acid is 23-53% protein bound in plasma. |
| Groups | Approved |
| Therapeutic Class | Bisphosphonate preparations |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Zoledronic Acid is used for:
- Hypercalcaemia of malignancy,
- Bone metastases associated with solid tumours, Osteolytic lesions associated with multiple myeloma,
- Corticosteroid-induced osteoporosis, Increase bone mass in men with osteoporosis, Osteoporosis in postmenopausal women
- Paget's disease of bone
- Prophylaxis of postmenopausal osteoporosis
Zoledronate is also used to associated treatment for these conditions: Bone Metastases, Hypercalcemia of Malignancy, Multiple Myeloma (MM), Osteoporosis, Osteoporosis caused by Glucocorticoid Treatment, Osteoporosis caused by glucocorticoid, Paget's Disease of Bone, Paget’s Disease, Bone Mineral Density
How Zoledronate works
Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis. Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act.
Osteoclasts mediate resorption of bone. When osteoclasts bind to bone they form podosomes, ring structures of F-actin. Etidronic acid also inhibits V-ATPases in the osteoclast, though the exact subunits are unknown, preventing F-actin from forming podosomes. Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption.
Nitrogen containing bisphosphonates such as zoledronate are known to induce apoptosis of hematopoietic tumor cells by inhibiting the components of the mevalonate pathway farnesyl diphosphate synthase, farnesyl diphosphate, and geranylgeranyl diphosphate. These components are essential for post-translational prenylation of GTP-binding proteins like Rap1. The lack of prenylation of these proteins interferes with their function, and in the case of Rap1, leads to apoptosis. zoledronate also activated caspases which further contribute to apoptosis.
Dosage
Zoledronate dosage
Hypercalcemia of malignancy: The maximum recommended dose of Zoledronic Acid in hypercalcemia of malignancy (serum calcium 12 mg/dl or 3.0 mmol/l) is 4 mg. The 4 mg dose must be given as a single-dose intravenous infusion. Dose adjustment of Zoledronic Acid is not necessary in treating patients for hypercalcemia of malignancy presenting with mild-to-moderate renal impairment. Re-treatment with Zoledronic Acid may be considered if serum calcium does not return to normal after initial treatment. It is recommended that a minimum of 7 days elapse before re-treatment, to allow for full response to the initial dose.Multiple myeloma and bone metastases of solid tumors: The recommended dose of Zoledronic Acid in patients with multiple myeloma and metastatic bone lesions from solid tumors is 4 mg infused every 3-4 weeks. Patients should also be administered an oral calcium supplement of 500 mg and 400 IU of Vitamin-D daily.
Prior to administration, the required amount of concentrate from one vial must be further diluted with 100 ml of calcium-free infusion solution (0.9% w/v sodium chloride solution or 5% w/v glucose solution). The duration of infusion must not be less than 15 minutes. After addition of the solution to the infusion media, the infusion solution should be used as soon as possible. If storage of the infusion solution is necessary, hold at 2-8º C for not more than 24 hours. If refrigerated, the solution must be allowed to reach room temperature before administration.Zoledronic Acid must not be mixed with calcium or other divalent cation-containing infusion solutions, such as Lactated Ringer's solution, and should be administered as a single intravenous solution in a line separate from all other drugs.
Side Effects
The post-dose side-effects are headache, nausea, anorexia, fatigue, osteonecrosis of jaw, anemia, bone pain, constipation, fever, vomiting, flu-like syndrome, hypocalcemia, myalgia, arthralgia and hypophosphataemia.
Toxicity
Patients experiencing an overdose may present with renal impairment, hypocalcemia, hypophosphatemia, and hypomagnesemia. Overdose should be managed through intravenous administration of the insufficient ions.
Precaution
Patients must be appropriately hydrated prior to administration of Zoledronic Acid. This is especially important in the elderly and for patients receiving diuretic therapy. Adequate hydration can be achieved by the patient drinking two glasses of fluid (such as water) before and after the infusion. Serum levels of calcium, phosphate, magnesium and potassium, as well as serum creatinine should be carefully monitored after initiating Zoledronic Acid therapy. If hypocalcemia, hypophosphatemia or hypomagnesemia occurs, short-term supplemental therapy may be necessary. Moreover, careful renal function monitoring should be considered.
Interaction
In clinical studies, Zoledronate has been administered concomitantly with commonly used anticancer agents, diuretics, antibiotics and analgesics without interactions. Caution is advised when Zoledronate are administered with aminoglycosides, since these agents may have an additive effect to lower serum calcium level for prolonged periods. In multiple myeloma patients, the risk of renal dysfunction may be increased when Zoledronate is used in combination with thalidomide. Concomitant use of loop diuretics with Zoledronate increases the risk of hypocalcemia. Caution is indicated when Zoledronate is used with other potentially nephrotoxic drugs.
Food Interaction
No interactions found.Elimination Route
A 4mg intravenous dose reaches a Cmax of 370±78.5ng/mL, with a Tmax of 0.317±0.014h, and an AUC of 788±181ng*h/mL. A 5mg intravenous dose reaches a Cmax of 471±76.1ng/mL, with a Tmax of 0.368±0.005h, and an AUC of 917±226ng*h/mL.
Half Life
Zoledronate has a terminal elimination half life of 146 hours.
Clearance
Zoledronate has a renal clearance of 3.7 ± 2.0 L/h.
Elimination Route
Zoledronate is 39 ± 16% eliminated in the urine as the unmetabolized parent drug.
Pregnancy & Breastfeeding use
Zoledronate is contraindicated during pregnancy and in breast-feeding women. It is also not recommended for use in children and adolescents below 18 years of age.
Contraindication
The drug is contraindicated if patients have hypersensitivity to the active substance or to any of the excipients or to any bisphosphonates; severe renal impairment (Creatinine clearance <30 ml/min); pregnancy and lactation.
Special Warning
Patients with renal impairment: The use of Zoledronic Acid is not recommended in patients with severe renal impairment (Creatinine clearance <30 ml/min). No dose adjustment is necessary in patients with creatinine clearance >60 ml/min. Based on creatinine clearance the following dose should be used in patient with impaired renal function:
- CrCl > 60 ml/min: 4 mg (5 ml)
- CrCl 50-60 ml/min: 3.5 mg (4.4 ml)
- CrCl 40-49 ml/min: 3.3 mg (4.1 ml)
- CrCl 30-39 ml/min: 3 mg (3.8 ml)
Acute Overdose
Clinical experience with acute over dosage is limited. Over dosage may cause hypocalcemia, hypophosphatemia, and hypomagnesemia. In such case, reduction 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.
Storage Condition
Store below 30° C prior to opening. Protect from moisture and light. Zoledronic Acid must be kept out of the reach and sight of children.
Innovators Monograph
You find simplified version here Zoledronate
Zoledronate contains Zoledronic acid see full prescribing information from innovator Zoledronate Monograph, Zoledronate MSDS, Zoledronate FDA label
FAQ
What is the use of Zoledronate?
Zoledronate is used to treat high blood calcium levels that may occur with cancer.Zoledronate is also used with cancer chemotherapy to treat bone problems that may occur with multiple myeloma and other types of cancer (such as breast, lung) that have spread to the bones.
How safe is Zoledronate?
Zoledronate had an acceptable safety profile; no adverse events were considered to be drug related. Treatment with Zoledronate improved bone health by enhancing bone mineral density and reducing bone turnover, even in high-risk patients.
How effective is Zoledronate?
Zoledronate was significantly more effective than placebo on most efficacy measures in patients with bone metastases secondary to other solid tumours and showed sustained efficacy for up to 15 months.
What are the long term side effects of Zoledronate?
- Blurred vision or other change in vision.
- decreased frequency or amount of urine.
- decreased vision.
- eye pain.
- eye tenderness.
- heavy jaw feeling.
- increased blood pressure.
- increased tearing.
How fast does Zoledronate work?
Zoledronate can take 2 to 3 months before you notice the full effects.
Does Zoledronate affect my teeth?
If you are having dental procedures while receiving this Zoledronate, you may have an increased chance of having a severe problem with your jaw.
Does Zoledronate cause bone pain?
Zoledronate can cause bone, joint and/or muscle pain that can be severe. This can occur from 1 day to several months after starting the medication.
Does Zoledronate affect my immune system?
Zoledronate can affects the immune system and inflammation, and both of those are important in fighting infection and cardiovascular disease.
Does Zoledronate affect kidneys?
Zoledronate is associated with reports of renal impairment and renal failure, especially in patients with pre-existing renal dysfunction or other risk factors. Renal function should be measured before each dose, and patients should be adequately hydrated before treatment.
Does Zoledronate strengthen bones?
Zoledronate is an osteoporosis medication prescribed to help strengthen your bones and reduce your risk of breaking a bone. It is available as an annual intravenous infusion (drip).Brand is a 'bisphosphonate' - a group of medications that work by slowing down the cells that break down bone.
Why is Zoledronate given once a year?
Zoledronate is given once a year as an intravenous (IV) infusion to treat osteoporosis. It is also given every two years as an IV infusion to prevent osteoporosis. Zoledronate increases bone density and reduces the incidence of the spine and non-spine fractures, including hip fractures.
How long does a Zoledronate infusion take?
The infusion time must not be less than 15 minutes and the infusion rate should be constant.
Does Zoledronate cause atrial fibrillation?
Zoledronate is associated with a 25% increased risk of atrial fibrillation during its first year of use for osteoporosis compared to treatment with denosumab.
What happens after Zoledronate infusion?
The majority of the side effects, such as fever and chills, pain in the muscles or joints, and headache, occur within the first three days following the dose of Zoledronate 5 mg. The symptoms are usually mild to moderate and go away within three days.
How long does Zoledronate stay in my body?
Zoledronate medication is a long-acting drug. As such, it stays in your body longer than 12 months (probably more than 24 months).
How do I give Zoledronate injection?
Zoledronate(5 mg in 100 ml ready-to-infuse solution) is administered via a vented infusion line and given slowly at a constant infusion rate. The infusion time must not be less than 15 minutes.
Can Zoledronate be taken orally?
Reclast and Zometa Zoledronate are administered by intravenous (IV) injection once a year. The other bisphosphonates come in pills, taken orally.
Does Zoledronate make me tired?
Zoledronate may cause changes in the blood. For example, it can cause low levels of red blood cells (anaemia). Symptoms of anaemia include feeling very tired and breathless.
Does Zoledronate affect the heart?
Patients treated with Zoledronate had a higher risk for heart failure, among other cardiovascular conditions, according to a study presented at the American Society for Bone and Mineral Research (ASBMR) 2017 Annual Meeting held September 8-11 in Denver, Colorado.
Does Zoledronate cause diarrhea?
Oral non-aminobisphosphonates are known to cause diarrhoea that is usually mild and self-limited.
Is Zoledronate a chemo drug?
Zoledronate is not cancer chemotherapy.Zoledronate is in a class of medications called bisphosphonates.
How soon does Zoledronate start working?
Zoledronate can take 2 to 3 months before you notice the full effects. If you are having Zoledronate to lower calcium levels in your blood, it is usually given as a single dose.
