Ibandronic acid: Difference between revisions

Ibandronic acid
Clinical data
Trade names	Boniva, Bonviva, Bondronat, others
AHFS/Drugs.com	Monograph
License data	EU EMA: by INN; US DailyMed: Ibandronate_sodium; US FDA: Ibandronate_sodium;
Pregnancy; category	AU: B3; ;
Routes of; administration	By mouth, intravenous
ATC code	M05BA06 (WHO) ;
Legal status
Legal status	US: ℞-only; EU: Rx-only; In general: ℞ (Prescription only);
Pharmacokinetic data
Bioavailability	0.6%
Protein binding	90.9 to 99.5%; (concentration-dependent)
Metabolism	Nil
Elimination half-life	10 to 60 hours
Excretion	Kidney
Identifiers
	IUPAC name Hydroxy-[1-hydroxy-3-[methyl(pentyl)amino]-1-phosphonopropyl]phosphinate;
CAS Number	114084-78-5 ;
PubChem CID	60852;
IUPHAR/BPS	3059;
DrugBank	DB00710 ;
ChemSpider	54839 ;
UNII	UMD7G2653W;
KEGG	D08056 ; as salt: D04486 ;
ChEBI	CHEBI:93770;
ChEMBL	ChEMBL997 ;
PDB ligand	BFQ (PDBe, RCSB PDB);
CompTox Dashboard (EPA)	DTXSID5048340 ;
ECHA InfoCard	100.214.537
Chemical and physical data
Formula	C9H23NO7P2
Molar mass	319.231 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=P(O)(O)C(O)(CCN(CCCCC)C)P(=O)(O)O;
	InChI InChI=1S/C9H23NO7P2/c1-3-4-5-7-10(2)8-6-9(11,18(12,13)14)19(15,16)17/h11H,3-8H2,1-2H3,(H2,12,13,14)(H2,15,16,17) ; Key:MPBVHIBUJCELCL-UHFFFAOYSA-N ;
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Ibandronic acid is a bisphosphonate medication used in the prevention and treatment of osteoporosis and metastasis-associated skeletal fractures in people with cancer.^[1] It may also be used to treat hypercalcemia (elevated blood calcium levels). It is typically formulated as its sodium salt ibandronate sodium.

It was patented in 1986 by Boehringer Mannheim and approved for medical use in 1996.^[2]

Medical uses

Ibandronate is indicated for the treatment and prevention of osteoporosis in post-menopausal women.^[3] In May 2003, the U.S. Food and Drug Administration (FDA) approved Ibandronate as a daily treatment for post-menopausal osteoporosis. The basis for this approval was a three-year, randomized, double-blind, placebo-controlled trial women with post-menopausal osteoporosis. Every participant also received daily oral doses of calcium and 400IUs [international units] of vitamin D. At the study's conclusion, both doses significantly reduced the occurrence risk of new vertebral fractures by 50–52 percent when compared to the effects of the placebo drug.

Ibandronate is efficacious for the prevention of metastasis-related bone fractures in multiple myeloma, breast cancer, and certain other cancers.^[4]

Adverse effects

In 2008, the U.S. Food and Drug Administration (FDA) issued a communication warning of the possibility of severe and sometimes incapacitating bone, joint or muscle pain.^[5] A study conducted by the American Society of Bone and Mineral Research concluded that long-term use of bisphosphonates, including Boniva, may increase the risk of a rare but serious fracture of the femur. ^[6] The drug also has been associated with osteonecrosis of the jaw, relatively rare but serious condition.^[7]

Pharmacology

Relative potency^[8]
Bisphosphonate	Relative potency
Etidronate	1
Tiludronate	10
Pamidronate	100
Alendronate	100-500
Ibandronate	500-1000
Risedronate	1000
Zoledronate	5000

Brand names

Ibandronic acid is marketed under the trade names Boniva in the US, Bondronat in Europe, Bonviva in Asia, Bandrone in India, Ibandrix in Ecuador, Adronil in Pakistan, Bondrova in Bangladesh and Bonprove in Egypt, Fosfonat in Mexico.

References

^ Bauss F, Schimmer RC (March 2006). "Ibandronate: the first once-monthly oral bisphosphonate for treatment of postmenopausal osteoporosis". Therapeutics and Clinical Risk Management. 2 (1): 3–18. PMC 1661644. PMID 18360577.
^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 523. ISBN 9783527607495.
^ "Boniva". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.
^ Sittig HB (2012). "Pathogenesis and bisphosphonate treatment of skeletal events and bone pain in metastatic cancer: focus on ibandronate". Onkologie. 35 (6): 380–7. doi:10.1159/000338947. PMID 22722461. S2CID 8413102.
^ "Information for Healthcare Professionals: Bisphosphonates (marketed as Actonel, Actonel+Ca, Aredia, Boniva, Didronel, Fosamax, Fosamax+D, Reclast, Skelid, and Zometa)". U.S. Food and Drug Administration. Retrieved 27 October 2010.
^ Shane E, Burr D, Ebeling PR, Abrahamsen B, Adler RA, Brown TD, et al. (American Society for Bone and Mineral Research) (November 2010). "Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research". Journal of Bone and Mineral Research. 25 (11): 2267–2294. doi:10.1002/jbmr.253. PMID 20842676. S2CID 15194275.; Lay summary in: "JBMR Publishes ASBMR Task Force Report on Atypical Femoral Fractures". Journal of Bone and Mineral Research. 14 September 2010. Archived from the original on 9 April 2016. Retrieved 27 October 2010.
^ "Osteonecrosis of the jaw (ONJ) and drug treatments for osteoporosis" (PDF). United Kingdom: The National Osteoporosis Society. Archived from the original (PDF) on 2017-06-17. Retrieved 2018-08-14.
^ Tripathi KD (2013-09-30). Essentials of Medical Pharmacology (Seventh ed.). New Delhi: Jaypee Brothers Medical Publisher. ISBN 9789350259375. OCLC 868299888.

External links

"Ibandronic acid". Drug Information Portal. U.S. National Library of Medicine.

[pmid18360577-1] Bauss F, Schimmer RC (March 2006). "Ibandronate: the first once-monthly oral bisphosphonate for treatment of postmenopausal osteoporosis". Therapeutics and Clinical Risk Management. 2 (1): 3–18. PMC 1661644. PMID 18360577.

[Fis2006-2] Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 523. ISBN 9783527607495.

[AHFS-3] "Boniva". The American Society of Health-System Pharmacists. Retrieved 3 April 2011.

[4] Sittig HB (2012). "Pathogenesis and bisphosphonate treatment of skeletal events and bone pain in metastatic cancer: focus on ibandronate". Onkologie. 35 (6): 380–7. doi:10.1159/000338947. PMID 22722461. S2CID 8413102.

[5] "Information for Healthcare Professionals: Bisphosphonates (marketed as Actonel, Actonel+Ca, Aredia, Boniva, Didronel, Fosamax, Fosamax+D, Reclast, Skelid, and Zometa)". U.S. Food and Drug Administration. Retrieved 27 October 2010.

[pmid20842676-6] Shane E, Burr D, Ebeling PR, Abrahamsen B, Adler RA, Brown TD, et al. (American Society for Bone and Mineral Research) (November 2010). "Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research". Journal of Bone and Mineral Research. 25 (11): 2267–2294. doi:10.1002/jbmr.253. PMID 20842676. S2CID 15194275.; Lay summary in: "JBMR Publishes ASBMR Task Force Report on Atypical Femoral Fractures". Journal of Bone and Mineral Research. 14 September 2010. Archived from the original on 9 April 2016. Retrieved 27 October 2010.

[7] "Osteonecrosis of the jaw (ONJ) and drug treatments for osteoporosis" (PDF). United Kingdom: The National Osteoporosis Society. Archived from the original (PDF) on 2017-06-17. Retrieved 2018-08-14.

[8] Tripathi KD (2013-09-30). Essentials of Medical Pharmacology (Seventh ed.). New Delhi: Jaypee Brothers Medical Publisher. ISBN 9789350259375. OCLC 868299888.

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@@ Line 1: / Line 1: @@
+{{Short description|Chemical compound}}
-{{Drugbox
+{{Infobox drug
 | Verifiedfields = changed
 | Watchedfields = changed
 | verifiedrevid = 461936767
+| image = Ibandronic acid.svg
-| IUPAC_name = {1-Hydroxy-3-[methyl(pentyl)amino]propane-1,1-diyl}bis(phosphonic acid)
-| image = Ibandronate.svg
 <!--Clinical data-->
-| tradename =
+| tradename = Boniva, Bonviva, Bondronat, others
-| Drugs.com = {{drugs.com|international|ibandronic-acid}}
+| Drugs.com = {{drugs.com|monograph|ibandronate-sodium}}
 | licence_EU = yes
+| DailyMedID = Ibandronate_sodium
-| licence_US = ibandronate_sodium
+| licence_US = Ibandronate_sodium
+| pregnancy_AU = B3
 | pregnancy_US = C
+| legal_US = Rx-only
+| legal_EU = Rx-only
 | legal_status = Rx-only
-| routes_of_administration = Oral, [[intravenous therapy|intravenous]]
+| routes_of_administration = [[Oral administration|By mouth]], [[intravenous therapy|intravenous]]
+| ATC_prefix = M05
+| ATC_suffix = BA06
 <!--Pharmacokinetic data-->
 | bioavailability = 0.6%
-| protein_bound = 90.9 to 99.5%<br>(concentration-dependent)
+| protein_bound = 90.9 to 99.5%<br />(concentration-dependent)
 | metabolism = Nil
 | elimination_half-life = 10 to 60 hours
-| excretion = [[Kidney|Renal]]
+| excretion = [[Kidney]]
 <!--Identifiers-->
+| index2_label = as salt
 | IUPHAR_ligand = 3059
 | CAS_number_Ref = {{cascite|correct|??}}
 | CAS_number = 114084-78-5
-| ATC_prefix = M05
-| ATC_suffix = BA06
 | PubChem = 60852
 | DrugBank_Ref = {{drugbankcite|changed|drugbank}}
@@ Line 34: / Line 42: @@
 | KEGG_Ref = {{keggcite|correct|kegg}}
 | KEGG = D08056
+| KEGG2_Ref = {{keggcite|correct|kegg}}
+| KEGG2 = D04486
+| ChEBI_Ref         =
+| ChEBI             = 93770
 | ChEMBL_Ref = {{ebicite|correct|EBI}}
 | ChEMBL = 997
+| NIAID_ChemDB      =
+| PDB_ligand        = BFQ
+| synonyms          =
 <!--Chemical data-->
+| IUPAC_name        = Hydroxy-[1-hydroxy-3-[methyl(pentyl)amino]-1-phosphonopropyl]phosphinate
 | C=9 | H=23 | N=1 | O=7 | P=2
 | smiles = O=P(O)(O)C(O)(CCN(CCCCC)C)P(=O)(O)O
@@ Line 44: / Line 61: @@
 | StdInChIKey = MPBVHIBUJCELCL-UHFFFAOYSA-N
 }}
 <!-- Definition and medical uses -->
-'''Ibandronic acid''' or '''ibandronate sodium''' is a [[bisphosphonate]] medication used in the prevention and treatment of [[osteoporosis]] and metastasis-associated skeletal fractures in people with cancer.<ref name="pmid18360577">{{cite journal | vauthors = Bauss F, Schimmer RC | title = Ibandronate: the first once-monthly oral bisphosphonate for treatment of postmenopausal osteoporosis | journal = Therapeutics and Clinical Risk Management | volume = 2 | issue = 1 | pages = 3–18 | date = March 2006 | pmid = 18360577 | pmc = 1661644 | doi =  }}</ref> It may also be used to treat [[hypercalcaemia|hypercalcemia]] (elevated blood [[calcium]] levels).
+'''Ibandronic acid''' is a [[bisphosphonate]] medication used in the prevention and treatment of [[osteoporosis]] and metastasis-associated skeletal fractures in people with cancer.<ref name="pmid18360577">{{cite journal | vauthors = Bauss F, Schimmer RC | title = Ibandronate: the first once-monthly oral bisphosphonate for treatment of postmenopausal osteoporosis | journal = Therapeutics and Clinical Risk Management | volume = 2 | issue = 1 | pages = 3–18 | date = March 2006 | pmid = 18360577 | pmc = 1661644 }}</ref> It may also be used to treat [[hypercalcaemia|hypercalcemia]] (elevated blood [[calcium]] levels).  It is typically [[Pharmaceutical formulation|formulated]] as its [[sodium]] [[salt (chemistry)|salt]] '''ibandronate sodium'''.
 <!-- Society and culture -->
-It was patented in 1986 by [[Boehringer Mannheim]] and approved for medical use in 1996.<ref name=Fis2006>{{cite book |last1=Fischer |first1=Jnos |last2=Ganellin |first2=C. Robin | name-list-format = vanc |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=523 |url=https://books.google.ca/books?id=FjKfqkaKkAAC&pg=PA523 |language=en}}</ref>
+It was patented in 1986 by [[Boehringer Mannheim]] and approved for medical use in 1996.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=9783527607495 |page=523 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA523 }}</ref>
 ==Medical uses==
-Ibandronate is indicated for the treatment and prevention of osteoporosis in post-menopausal women.<ref name=AHFS>{{cite web|title=boniva|url=https://www.drugs.com/monograph/boniva.html|work=The American Society of Health-System Pharmacists|access-date=3 April 2011}}</ref> In May 2003, the U.S. [[Food and Drug Administration]] (FDA) approved Ibandronate as a daily treatment for post-menopausal osteoporosis. The basis for this approval was a three-year, [[randomized controlled trial|randomized]], [[double blind|double-blind]], [[placebo]]-controlled [[clinical trial|trial]] women with post-menopausal osteoporosis. Every participant also received daily oral doses of [[calcium]] and 400IUs [international units] of [[vitamin D]]. At the study's conclusion, both doses significantly reduced the occurrence risk of new vertebral fractures by 50–52 percent when compared to the effects of the placebo drug.
+Ibandronate is indicated for the treatment and prevention of osteoporosis in post-menopausal women.<ref name=AHFS>{{cite web|title= Boniva|url=https://www.drugs.com/monograph/boniva.html |work=The American Society of Health-System Pharmacists |access-date=3 April 2011}}</ref> In May 2003, the U.S. [[Food and Drug Administration]] (FDA) approved Ibandronate as a daily treatment for post-menopausal osteoporosis. The basis for this approval was a three-year, [[randomized controlled trial|randomized]], [[double blind|double-blind]], [[placebo]]-controlled [[clinical trial|trial]] women with post-menopausal osteoporosis. Every participant also received daily oral doses of [[calcium]] and 400IUs [international units] of [[vitamin D]]. At the study's conclusion, both doses significantly reduced the occurrence risk of new vertebral fractures by 50–52 percent when compared to the effects of the placebo drug.
-Ibandronate is efficacious for the prevention of metastasis-related bone fractures in multiple myeloma, breast cancer, and certain other cancers.<ref>{{cite journal | vauthors = Sittig HB | title = Pathogenesis and bisphosphonate treatment of skeletal events and bone pain in metastatic cancer: focus on ibandronate | journal = Onkologie | volume = 35 | issue = 6 | pages = 380–7 | year = 2012 | pmid = 22722461 | doi = 10.1159/000338947 }}</ref>
+Ibandronate is efficacious for the prevention of metastasis-related bone fractures in multiple myeloma, breast cancer, and certain other cancers.<ref>{{cite journal | vauthors = Sittig HB | title = Pathogenesis and bisphosphonate treatment of skeletal events and bone pain in metastatic cancer: focus on ibandronate | journal = Onkologie | volume = 35 | issue = 6 | pages = 380–7 | year = 2012 | pmid = 22722461 | doi = 10.1159/000338947 | s2cid = 8413102 }}</ref>
 ==Adverse effects==
-In 2008, the U.S [[Food and Drug Administration]] (FDA) issued a communication warning of the possibility of severe and sometimes incapacitating bone, joint or muscle pain.<ref>{{Cite web|url=https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124165.htm|title=Information for Healthcare Professionals: Bisphosphonates (marketed as Actonel, Actonel+Ca, Aredia, Boniva, Didronel, Fosamax, Fosamax+D, Reclast, Skelid, and Zometa)|publisher=U.S. Food and Drug Administration|access-date=27 October 2010}}</ref> A study conducted by the American Society of Bone and Mineral Research concluded that long-term use of [[bisphosphonates]], including Boniva, may increase the risk of a rare but serious fracture of the femur.
+In 2008, the U.S. [[Food and Drug Administration]] (FDA) issued a communication warning of the possibility of severe and sometimes incapacitating bone, joint or muscle pain.<ref>{{Cite web|url=https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm124165.htm|title=Information for Healthcare Professionals: Bisphosphonates (marketed as Actonel, Actonel+Ca, Aredia, Boniva, Didronel, Fosamax, Fosamax+D, Reclast, Skelid, and Zometa)|publisher=U.S. Food and Drug Administration|access-date=27 October 2010}}</ref> A study conducted by the American Society of Bone and Mineral Research concluded that long-term use of [[bisphosphonates]], including Boniva, may increase the risk of a rare but serious fracture of the femur.
-<ref>{{Cite web|url=http://www.asbmr.org/about/pressreleases/detail.aspx?cid=a68f2b70-a117-4094-9f6f-b5993c6a6149|title=Drugs Commonly Prescribed for Osteoporosis Patients are Effective at Reducing Risk of Hip and Spine Fractures, But Panel Says May be Related to Unusual Thigh Bone Fractures When Used Long Term |publisher=Journal of Bone and Mineral Research=27 October 2010}}</ref> The drug also has been associated with [[osteonecrosis of the jaw]], relatively rare but serious condition.<ref>{{Cite web|url=https://nos.org.uk/media/1593/k-drug-treatments-for-osteoporosis-osteonecrosis-of-the-jaw-onj-_.pdf|title=Osteonecrosis of the jaw (ONJ) and drug treatments for osteoporosis|last=|first=|date=|website=nos.org.uk|publisher=The National Osteoporosis Society|archive-url=|archive-date=|access-date=}}</ref>
+<ref name="pmid20842676">{{cite journal | vauthors = Shane E, Burr D, Ebeling PR, Abrahamsen B, Adler RA, Brown TD, Cheung AM, Cosman F, Curtis JR, Dell R, Dempster D, Einhorn TA, Genant HK, Geusens P, Klaushofer K, Koval K, Lane JM, McKiernan F, McKinney R, Ng A, Nieves J, O'Keefe R, Papapoulos S, Sen HT, van der Meulen MC, Weinstein RS, Whyte M | display-authors = 6 | title = Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research | journal = Journal of Bone and Mineral Research | volume = 25 | issue = 11 | pages = 2267–2294 | date = November 2010 | pmid = 20842676 | doi = 10.1002/jbmr.253 | s2cid = 15194275 | collaboration = American Society for Bone and Mineral Research | doi-access = free }}; {{lay source | title = JBMR Publishes ASBMR Task Force Report on Atypical Femoral Fractures |url=http://www.asbmr.org/about/pressreleases/detail.aspx?cid=a68f2b70-a117-4094-9f6f-b5993c6a6149 |publisher=Journal of Bone and Mineral Research | date  = 14 September 2010 |access-date=27 October 2010|archive-date=9 April 2016|archive-url=https://web.archive.org/web/20160409074649/http://www.asbmr.org/about/pressreleases/detail.aspx?cid=a68f2b70-a117-4094-9f6f-b5993c6a6149|url-status=dead}}</ref> The drug also has been associated with [[osteonecrosis of the jaw]], relatively rare but serious condition.<ref>{{Cite web|url=https://nos.org.uk/media/1593/k-drug-treatments-for-osteoporosis-osteonecrosis-of-the-jaw-onj-_.pdf|title=Osteonecrosis of the jaw (ONJ) and drug treatments for osteoporosis | location = United Kingdom |publisher=The National Osteoporosis Society|access-date=2018-08-14|archive-date=2017-06-17|archive-url=https://web.archive.org/web/20170617084719/https://nos.org.uk/media/1593/k-drug-treatments-for-osteoporosis-osteonecrosis-of-the-jaw-onj-_.pdf|url-status=dead}}</ref>
 == Pharmacology ==
 {| class="wikitable"
-|+Relative potency<ref>{{Cite book|title=Essentials of medical pharmacology | vauthors = Tripathi KD |isbn=9789350259375|edition= Seventh|location=New Delhi|oclc=868299888|date = 2013-09-30}}</ref>
+|+Relative potency<ref>{{Cite book|title=Essentials of Medical Pharmacology | vauthors = Tripathi KD |isbn=9789350259375|edition= Seventh|location=New Delhi | publisher = Jaypee Brothers Medical Publisher |oclc=868299888|date = 2013-09-30}}</ref>
 !Bisphosphonate
 !Relative potency
@@ Line 89: / Line 107: @@
 ==Brand names==
-Ibandronic acid is marketed under the trade names Boniva in the USA, Bondronat in Europe, Bonviva in Asia, Bandrone in India, Ibandrix in Ecuador, Adronil in Pakistan, Bondrova in Bangladesh and Bonprove in Egypt.
+Ibandronic acid is marketed under the trade names Boniva in the US, Bondronat in Europe, Bonviva in Asia, Bandrone in India, Ibandrix in Ecuador, Adronil in Pakistan, Bondrova in Bangladesh and Bonprove in Egypt, Fosfonat in Mexico.
 == References ==
@@ Line 95: / Line 113: @@
 == External links ==
+* {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/ibandronic%20acid | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Ibandronic acid }}
-* [http://www.ebi.ac.uk/pdbe-srv/PDBeXplore/ligand/?ligand=BFQ Ibandronate bound to proteins] in the [[Protein Data Bank|PDB]]
-* [http://www.boniva.com Boniva Osteoporosis Treatment by [[GlaxoSmithKline]] and [[Roche Laboratories]]]
-* [http://www.drugcite.com?q=BONIVA Boniva adverse events reported to the FDA]
 {{Bisphosphonates}}
 {{GlaxoSmithKline}}
+{{Portal bar | Medicine}}
 [[Category:Amines]]
 [[Category:Bisphosphonates]]
 [[Category:Farnesyl pyrophosphate synthase inhibitors]]
-[[Category:Hoffmann-La Roche brands]]
+[[Category:Drugs developed by Hoffmann-La Roche]]
-[[Category:Genentech brands]]
+[[Category:Drugs developed by Genentech]]
-[[Category:GlaxoSmithKline brands]]
+[[Category:Drugs developed by GSK plc]]

v t e Drugs for treatment of bone diseases (M05)
Bisphosphonates	Nitrogenous Alendronic acid Ibandronic acid Incadronic acid Minodronic acid Neridronic acid Pamidronic acid Risedronic acid Zoledronic acid Non-nitrogenous Etidronic acid Clodronic acid Tiludronic acid
Bone morphogenetic proteins	Dibotermin alfa Eptotermin alfa
Other	Resorption inhibitor Ipriflavone Aluminium chlorohydrate Dual action bone agent Strontium ranelate RANKL inhibitor Denosumab Sclerostin inhibitor Romosozumab Cathepsin K inhibitor Odanacatib Parathyroid hormone-related protein analogues Abaloparatide Teriparatide Calcitonin Calcium Vitamin D