Zoledronic acid
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| Non-proprietary name | Zoledronic acid | |||||||||||||||
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[1-Hydroxy-2- (imidazol-1-yl) ethylidene] diphosphonic acid ( IUPAC ) |
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| Brief description |
white crystalline powder |
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firmly |
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| Melting point |
239 ° C (zoledronic acid) |
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| As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions . | ||||||||||||||||
Zoledronic acid (also: zoledronate ) is a drug that inhibits the breakdown of bone tissue . It is used in the treatment of skeletal disorders such as osteoporosis and Paget's disease . Zoledronic acid is also indicated for the prevention of bone complications in cancer patients whose disease affects the bones and for the treatment of tumor-related , excessively high calcium levels in the blood.
Chemically, it is a substance from the group of bisphosphonates . Zoledronic acid was developed by Novartis .
Mechanism of action
Zoledronic acid reduces bone breakdown by blocking the osteoclasts . The osteoclasts are responsible for the resorption of the bone substance.
Clinical information
Areas of application and type of application
- Zometa
Zoledronic acid has been approved as Zometa since 2003 for the treatment of tumor-induced hypercalcemia ( TIH ) and for the prevention of skeletal complications in patients with advanced tumor diseases that extend to the skeleton. In addition to the inhibition of bone resorption, various anti-tumor activities have been demonstrated in clinical studies that could contribute to the overall effect. By inhibiting resorption, the susceptibility of the bone marrow to the growth of tumor cells is reduced, and anti-angiogenic and analgesic effects have also been observed. In vitro , among other things, a direct cytostatic activity on tumor cells was determined.
Zometa is usually given as an intravenous infusion every three to four weeks .
- Aclasta
Zoledronic acid has been approved as Aclasta since 2005 for the treatment of osteodystrophia deformans (Paget's disease) and since 2007 for the treatment of postmenopausal osteoporosis in women. Osteodystrophia deformans is the second most common disease of bone metabolism after osteoporosis . It manifests itself through the thickening and deformation of bones and a reduced breaking strength. The cause has not been conclusively clarified - viral infections or genetic factors are assumed.
In the HORIZON-PFT study published in 2007 with 7765 patients with postmenopausal osteoporosis, zoledronic acid 5 mg reduced the relative risk of vertebral body fractures by 70% and the risk of hip fractures by 41% compared with placebo.
In 2008 the approval was extended to include the treatment of men with osteoporosis-related fracture risk . The extension also includes the reduction of fractures in men and postmenopausal women who have recently suffered an osteoporosis-related hip fracture . The latter indication extension is based on a clinical study with 2100 patients. According to these study data, the risk of a re-fracture can be reduced by 35%.
In 2009, the field of application was expanded to include the treatment of patients whose osteoporosis is associated with long-term treatment with glucocorticoids .
In contrast to other bisphosphonates, Aclasta is administered once a year as an intravenous infusion - and not, as usual, in the form of weekly tablets. One Aclasta vial contains 5 milligrams of active ingredient in 100 ml of water for injections.
Side effects
The side effects of zoledronic acid are similar to those of other intravenous bisphosphonates. They usually appear within the first few days after ingestion and subside within a few days. The most common side effects are flu-like symptoms and headaches. In addition, there may be fever, bone and joint pain, fatigue, gastrointestinal complaints in individual cases. According to the HORIZON study, treatment with zoledronic acid also developed atrial fibrillation in not a few patients (1.3%) , which had not previously been observed with bisphosphonates. Atrial fibrillation was below the rate expected for this age group and was not seen in other studies with zoledronic acid.
Since 2003 the occurrence of jaw necrosis after tooth extraction in connection with the administration of aminobisphosphonates has been described. Pine necrosis occurs almost exclusively in connection with the administration of zoledronic acid. In the area of a large west German city with 250,000 inhabitants and a catchment area of 1 million, a total of 169 patients from three oncological practices and the participating specialist clinics of a university clinic were examined. (…) In total, bisphosphonate-associated necroses of the jaw were found in 15 patients (9%). The most common aminobisphosphonate used was zoledronic acid. 47% of the patients received this in isolation, in a further 20% zoledronic acid was given in alternation with other bisphosphonates. 13% had received Aredia, 20% Bondronat. Pine necrosis occurred 50% after tooth extraction or spontaneously. Usually the lower jaw was affected, in 20% the upper and lower jaw.
Because of the occurrence or worsening of renal impairment with zoledronic acid, patients with poor kidney function were excluded from treatment with Aclasta in March 2010 . The Food and Drug Administration extended the warning or ban for its area (USA) in September 2011.
Trade names
Aclasta (D, A, CH), Reclast (USA), Zoledro-Denk (D), Zometa (D, A, CH)
literature
- Kenneth W. Lyles et al .: Zoledronic Acid and Clinical Fractures and Mortality after Hip Fracture . In: NEJM . November 2007, doi : 10.1056 / NEJMoa074941 (English).
- Ian R. Reid et al .: Fracture Prevention with Zoledronate in Older Women with Osteopenia . In: NEJM . October 2018, doi : 10.1056 / NEJMoa1808082 (English).
Web links
- Public Assessment Report (EPAR) of the European Medicines Agency (EMA) for: Zoledronic acid
Individual evidence
- ^ FDA - Full prescribing information for Zometa ® (PDF; 221 kB).
- ^ The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, pp. 1753-1754, ISBN 978-0-911910-00-1 .
- ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
- ↑ Specialist information Zometa ® , July 2009.
- ↑ Black et al. Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis. NEJM 2007; 356; 18; 1809-1822. Abstract PMID 17476007 .
- ↑ Once-yearly Aclasta ® approved in EU to treat osteoporosis in men and to reduce risk of new fractures following hip fracture both in men and postmenopausal women Novartis press release of September 30, 2008 (PDF; 96 kB) .
- ↑ Lyles KW et al .: Zoledronic acid and clinical fractures and mortality after hip fracture. N Engl J Med. 2007 Nov 1; 357 (18): 1799-809. Epub 2007 Sep 17. Full text (HTML) Full text (PDF) , PMID 17878149 .
- ↑ Result of the randomized HORIZON study published in the New England Journal of Medicine (NEJM 2007; 356: 1809-1822), here cited from: Deutsches Ärzteblatt , May 3, 2007 ( online ( Memento from April 3, 2015 in the Internet Archive )) .
- ↑ Gerhards F., Rana M., Maciejewski O., Smeets R .: Prospective cohort study on possible cofactors of bisphosphonate-associated pine necrosis; 59th Annual Meeting of the Working Group on Oral Surgery, Wiesbaden (May 21-23, 2009).
- ^ Red hand letter from Novartis, March 12, 2010.
- ↑ New contraindication and warning for zoledronic acid ( Memento from February 22, 2014 in the Internet Archive ).
