ZOLEDRONIC ACID FACTS- USE, SIDE EFFECTS, DOSE, PREPARATIONS, ACTIONS
ZOLEDRONIC ACID REVIEW:
Zoledronic acid is a drug of Bisphosphonates group. This drug is mainly used for strengthening bone. Other bisphosphonates include Etidronate, Pamidronate, RIsedronate, Ibandronate and Tilludronate. It is interesting that, bone is always in a constant state of remodeling. New bone tissue is laid down by osteoblast cell and old bone is removed by osteoclast cell. Zoledronic acid acts on osteoclasts and inhibits its action and thus strengthens bone.
ZOLEDRONIC ACID SOLD AS:
Zometa, Zomera, Aclasta, Reclast, Zoldonat, Zoldria etc
Protein binding: 22% (approximately)
Half-life: about 146 hours
Excretion: Renal (partial)
PREPARATIONS OF ZOLEDRONIC ACID:
Solution: 5 mg/100 ml
STORAGE OF ZOLEDRONIC ACID:
Unopened bottles should be kept at room temperature 15-30 C (59-86 F). Opened bottles of solution are stable for 24 hours at 2-8 C (36-46 F).
USE OF ZOLEDRONIC ACID:
This drug is used to prevent skeletal fracture in cancers such as multiple myeloma, prostate cancer, also in osteoporosis, to treat hypercalcemia of malignancy, Paget’s disease.
DOSE OF ZOLEDRONIC ACID:
Zoledronic acid is given intravenously over no less than 15 minutes. Administration of acetaminophen or ibuprofen may reduce infusion related reactions.
- For the treatment of postmenopausal osteoporosis, a single 5 mg infusion once a year is recommended.
- To prevent postmenopausal osteoporosis, the recommended dose is 5 mg in every two years.
- Paget’s disease of bone is treated with a single 5 mg infusion. 1500 mg of elemental calcium and 800 IU vitamin D daily, especially during the two weeks after the injection of zoledronic acid is recommended for the patients with Paget’s disease.
- For prevention or treatment of steroid-induced osteoporosis, the recommended dose is same as the treatment of postmenopausal osteoporosis (5 mg once yearly).
DRUG INTERACTIONS WITH ZOLEDRONIC ACID:
If zoledronic acid is combined with aminoglycoside antibiotics like gentamycin or any loop diuretics like furosemide or bumetanide, it may lead to decreased calcium level in blood. Zoledronic acid should be used with caution in patients who are taking drugs that affect kidney function because zoledronic acid causes reduced kidney function.
ZOLEDRONIC ACID in PREGNANCY and NURSING MOTHERS:
Zoledronic acid should not be administered to pregnant women. Women of childbearing age should be advised to use a reliable method of birth control. It is not established whether zoledronic acid is excreted in human milk or not. Since many drugs are excreted in human milk, and zoledronic acid binds to bone long-term, it is wise to avoid zoledronic acid for nursing women.
SIDE EFFECTS OF ZOLEDRONIC ACID:
The most common adverse reactions of zoledronic acid are
- Fatigue, anemia, muscle pain, fever, swelling of feet, flu like syndrome (after 1st dose)
- pain in hands and feet
- Severe bone, joint, and muscle pain may occur
- Low calcium levels may occur (that’s why adequate calcium and vitamin D intake is recommended)
- Reduced kidney function after administration of zoledronic acid has occurred.
- Osteonecrosis of the jaw
- Delayed healing and infection after tooth extraction
- Rare cases of severe allergic reactions involving shock, swelling of tongue, throat, and closure of airways have been reported.
HOW ZOLEDRONIC ACID WORKS:
- In addition to being a potent inhibitor of bone resorption, zoledronic acid also possesses anticancer properties that could contribute to its overall efficacy in the treatment of metastatic bone disease.
- In vivo, zoledronic acid alters the bone marrow microenvironment to make it less conducive to tumour cell growth, as well as inhibiting angiogenic activity
- In vitro, zoledronic acid inhibits osteoblast proliferation, exerts direct cytostatic and pro-apoptotic activity on tumour cells, produces synergistic effects with other anticancer drugs, and inhibits tumour cell adhesion and invasion
CONTRAINDICATIONS OF ZOLEDRONIC ACID:
It should not be used in reduced renal function or kidney disease. *ACUTE RENAL FAILURE MAY OCCUR, EVEN FATAL OUTCOME IS POSSIBLE. So creatinine clearance must be checked. If it is less than 35 ml/min, this drug must be avoided. It is contraindicated in hypocalcemia as well.
PRECAUTIONS FOR USE OF ZOLEDRONIC ACID:
Renal function should be seen before using zoledronic acid. Creatinine clearance, serum creatinine, SGPT should be checked.
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