Ibandronic acid

Structural formula
General
Non-proprietary name	Ibandronic acid
other names	[1-Hydroxy-3- (methylpentylamino) propylidene] diphosphonic acid ( IUPAC ); Ibandronate;
Molecular formula	C 9 H 23 NO 7 P 2 (ibandronic acid) ; C 9 H 22 NNaO 7 P 2 (ibandronic acid sodium salt) ;
External identifiers / databases
ECHA InfoCard	100.214.537
PubChem	60852
DrugBank	DB00710
Wikidata	Q166825
Drug information
ATC code	M05 BA06
Drug class	Bisphosphonates
Mechanism of action	Osteolysis inhibitors
properties
Molar mass	319.23 g mol −1 (ibandronic acid) ; 341.21 g mol −1 (ibandronic acid sodium salt) ;
Physical state	firmly
Melting point	84 ° C (decomposition)
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances	no GHS pictograms
	no GHS pictograms
H and P phrases	H: no H-phrases
	P: no P-phrases
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Ibandronic acid (syn. Ibandronate ) is a drug from the bisphosphonate group and is used in the therapy of postmenopausal osteoporosis and for the treatment of bone metastases in breast cancer .

Clinical information

Indications / possible uses

Ibandronic acid is approved for the treatment of osteoporosis in postmenopausal women with an increased risk of fractures, osteodystrophia deformans and tumor-associated hypercalcemia . It is also used for bone metastases. A reduction in the risk of vertebral fractures has been shown; efficacy in relation to femoral neck fractures has not been established. Ibandronic acid leads to a progressive net increase in bone mass and a decrease in the incidence of fractures by reducing the increased bone turnover towards premenopausal values in postmenopausal women.

Type and duration of application

The drug Bonviva ( Roche ) has been available as a monthly pill or as a 3-month injection since 2004 . It should significantly improve reliability ( compliance ) compared to daily use. Bondronat has been approved for the prevention of skeletal events in patients with breast cancer and bone metastases since October 2003. It can be administered orally in tablet form or intravenously as an infusion, including a 15-minute short infusion. The therapeutic goal of treating patients with breast cancer and bone metastases is to inhibit bone destruction by reducing fractures in the spine and the rest of the skeleton. In addition, bone pain is permanently relieved.

Contraindications (contraindications)

Hypersensitivity to ibandronic acid
The safety and effectiveness when used in children and adolescents under the age of 18 have not been studied.
Hypocalcaemia : Any existing hypocalcaemia must be corrected before starting ibandronic acid therapy. Other disorders of bone and mineral metabolism should also be effectively treated. A sufficient intake of calcium and vitamin D is important for all patients.

Drug interactions

Interactions with polyvalent cations

Concomitant intake with polyvalent cations can impair the effectiveness of ibandronic acid. It is a pharmacokinetic mechanism . The bioavailability of the drug is very low. When taken at the same time as polyvalent cations, stable, difficult-to-absorb complexes are formed, which can seriously worsen absorption.

Ibandronic acid should usually be taken on an empty stomach half an hour to an hour (depending on the preparation) before breakfast or at another time two hours apart from any food or drink with a glass of tap water. Calcium-containing foods including mineral water, antacids and mineral supplements should be avoided within 2 hours before and after taking ibandronic acid.

Use during pregnancy and breastfeeding

pregnancy

There are insufficient data from the use of ibandronic acid in pregnant women. Studies in laboratory rats have shown reproductive toxicity . The potential risk to humans is unknown. Therefore, its use is contraindicated during pregnancy .

Lactation

It is not known whether ibandronic acid is excreted in breast milk . Studies in lactating rats have shown low levels of ibandronic acid in milk after intravenous administration - it should not be used during breastfeeding.

Adverse effects (side effects)

Gastrointestinal problems are the main side effects. Some patients suffered damage to the jawbone. These so-called bisphosphonate-associated jaw osteonecrosis are a rare class effect of bisphosphonates. Tooth extractions under bisphosphonate therapy are often the decisive trigger for jaw necrosis. They mostly occur with parenteral administration, but there are also some cases described in the literature under oral therapy.

Pharmacological properties

Mechanism of action (pharmacodynamics)

Bisphosphonates such as ibandronic acid are analogues of pyrophosphate (POP) in which the oxygen atom is replaced by a carbon atom. They bind specifically to hydroxyapatite , are - when the bone is broken down - taken up by osteoclasts , inhibit their functions and thus bone breakdown. Since new bone formation is not impaired and continues, there is a gain in bone mass and a reduction in increased Ca ²⁺ concentrations in the blood. Ibandronic acid is a nitrogen- containing bisphosphonate and inhibits cholesterol biosynthesis , thereby interfering with the prenylation of small G-proteins such as Ras and Rho and thus permanently disrupting signal processing and the function of the osteoclasts.

Trade names

Monopreparations

Bondenza (A), Bondronat (A, CH, D), Bonviva (A, CH, D), Destara (A), various generics

Web links

Public Assessment Report (EPAR) of the European Medicines Agency (EMA) for: Bonviva
Public Assessment Report (EPAR) of the European Medicines Agency (EMA) for: Bondronat

literature

W. Forth, D. Henschler, W. Rummel: General and special pharmacology and toxicology . 9th edition. Urban & Fischer, Munich 2005, ISBN 3-437-42521-8 .
Christine Vetter: Osteoporosis: New bisphosphonate as a monthly tablet . In: Deutsches Ärzteblatt . tape 102 , no. 44 , 2005, pp. A-3043 ( online ).

Individual evidence

^ The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, p. 845, ISBN 978-0-911910-00-1 .
↑ Data sheet Ibandronate sodium salt from Sigma-Aldrich , accessed on April 4, 2011 ( PDF ).
↑ ^a ^b ^c ^d Bonviva: Summary of Product Characteristics, as of May 19, 2009 on the website of the European Medicines Agency (PDF; 484 kB).

[MerckIndex-1] The Merck Index . An Encyclopaedia of Chemicals, Drugs and Biologicals . 14th edition, 2006, p. 845, ISBN 978-0-911910-00-1 .

[Sigma-2] Data sheet Ibandronate sodium salt from Sigma-Aldrich , accessed on April 4, 2011 ( PDF ).

[Bonviva-3] Bonviva: Summary of Product Characteristics, as of May 19, 2009 on the website of the European Medicines Agency (PDF; 484 kB).