Drug/Small Molecule:
alendronate

PharmGKB contains no dosing guidelines for this drug/small molecule. To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB contains no drug labels with pharmacogenomic information for this drug/small molecule. To report a drug label with PGx, click here.

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs1256049 45724051C>T, 64724051C>T, 86218G>A, 984G>A, ESR2:1082G>A, ESR2:Val328Val, ESR2:rs1256049, Val328=
C > T
Not Available
Val328Val
rs1544410 1024+283G>A, 10383141C>T, 1174+283G>A, 48239835C>T, 63980G>A, VDR: BsmI, VDR:BsmI
C > T
Intronic
No VIP available CA No Variant Annotations available
rs2297480 -1-373T>G, -1-98T>G, -175+726T>G, -22-352T>G, 155279482T>G, 6768124T>G
T > G
Intronic
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Acide Alendronique [INN-French]
  • Acido Alendronico [INN-Spanish]
  • Acidum Alendronicum [INN-Latin]
  • Alendronate Sodium
  • Alendronic acid
Trade Names
  • Adronat
  • Alendros
  • Arendal
  • Fosamax
  • Fosamax Plus D
  • Onclast
Brand Mixture Names

PharmGKB Accession Id:
PA448082

Description

Alendronate is a nitrogen-containing, second generation bisphosphonate. Bisphosphonates were first used to treat Paget's disease in 1971. This class of medications is comprised of inorganic pyrophosphate analogues that contain non-hydrolyzable P-C-P bonds. Similar to other bisphosphonates, alendronate has a high affinity for bone mineral and is taken up during osteoclast resorption. Alendronate inhibits farnesyl pyrophosphate synthetase, one of the enzymes in the mevalonic acid pathway involved in producing isoprenoid compounds that are essential for post-translational modification of small guanosine triphosphate (GTP)-binding proteins, such as Rho, Ras and Rab. Inhibition of this process interferes with osteoclast function and survival. Alendronate is used for the treatment of osteoporosis and Paget's disease.

Source: Drug Bank

Indication

For the treatment and prevention of osteoporosis in women and Paget's disease of bone in both men and women.

Source: Drug Bank

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

The action of Alendronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Alendronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.

Source: Drug Bank

Pharmacology

Alendronate, a second-generation bisphosphonate is the first member of a group of drugs which strengthens bone. Alendronate is used to reduce hypercalcemia in tumor-induced bone disease, to treat corticosteroid-induced osteoporosis and Paget's disease, and to prevent osteoporosis in postmenopausal women.

Source: Drug Bank

Food Interaction

Take 30-60 minutes before breakfast.|Take with a full glass of water.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

There is no evidence that alendronate is metabolized in humans or animals.

Source: Drug Bank

Protein Binding

78%

Source: Drug Bank

Absorption

Relative to an intravenous (IV) reference dose, the mean oral bioavailability of alendronate in women was 0.7% for doses ranging from 5 to 40 mg when administered after an overnight fast and two hours before a standardized breakfast. Oral bioavailability of the 10 mg tablet in men (0.59%) was similar to that in women (0.78%) when administered after an overnight fast and 2 hours before breakfast.

Source: Drug Bank

Half-Life

>10 years

Source: Drug Bank

Toxicity

Alendronate can damage the esophagus both by toxicity from the medication itself and by nonspecific irritation secondary to contact between the pill and the esophageal mucosa, similar to other cases of "pill esophagitis."

Source: Drug Bank

Clearance

Source: Drug Bank

Route of Elimination

Following a single IV dose of [14C]alendronate, approximately 50% of the radioactivity was excreted in the urine within 72 hours and little or no radioactivity was recovered in the feces.

Source: Drug Bank

Volume of Distribution

  • 28 L

Source: Drug Bank

Chemical Properties

Chemical Formula

C4H13NO7P2

Source: Drug Bank

Isomeric SMILES

C(CC(O)(P(=O)(O)O)P(=O)(O)O)CN

Source: Drug Bank

NCCCC(O)(P(O)(O)=O)P(O)(O)=O

Source: Drug Bank

Canonical SMILES

NCCCC(O)(P(O)(O)=O)P(O)(O)=O

Source: Drug Bank

Average Molecular Weight

249.096

Source: Drug Bank

Monoisotopic Molecular Weight

249.016724799

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
ESR2
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
FDPS
VDR

Drug Targets

Gene Description
ATP6V1A (source: Drug Bank)
FDPS (source: Drug Bank)
PTPN4 (source: Drug Bank)
PTPRE (source: Drug Bank)
PTPRS (source: Drug Bank)

Drug Interactions

Drug Description
alendronate Formation of non-absorbable complexes (source: Drug Bank)
alendronate Formation of non-absorbable complexes (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Formation of non-absorbable complexes (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gasrtic toxicity (source: Drug Bank)
alendronate Increased risk of gasrtic toxicity (source: Drug Bank)
alendronate Formation of non-absorbable complexes (source: Drug Bank)
alendronate Formation of non-absorbable complexes (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)
alendronate Increased risk of gastric toxicity (source: Drug Bank)

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to alendronate: 18

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The future of pharmacogenetics for osteoporosis. Pharmacogenomics. 2013. Marini Francesca, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Very important pharmacogene summary for VDR. Pharmacogenetics and genomics. 2012. Poon Audrey H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
The effect of vitamin D receptor BsmI genotype on the response to osteoporosis treatment in postmenopausal women: a pilot study. The journal of obstetrics and gynaecology research. 2011. Creatsa Maria, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
BsmI vitamin D receptor's polymorphism and bone mineral density in men and premenopausal women on long-term antiepileptic therapy. European journal of neurology : the official journal of the European Federation of Neurological Societies. 2011. Lambrinoudaki I, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Bisphosphonates pathway. Pharmacogenetics and genomics. 2011. Gong Li, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Common allelic variants of the farnesyl diphosphate synthase gene influence the response of osteoporotic women to bisphosphonates. The pharmacogenomics journal. 2010. Olmos J M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics of osteoporosis-related bone fractures: moving towards the harmonization and validation of polymorphism diagnostic tools. Pharmacogenomics. 2010. Rojo Venegas Karen, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Vitamin D receptor gene polymorphisms predict acquired resistance to clodronate treatment in patients with Paget's disease of bone. Calcified tissue international. 2008. Mossetti Giuseppe, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Vitamin D receptor genotypes and response to zoledronic acid therapy in thalassemia-induced osteoporosis. Annals of hematology. 2008. Otrock Zaher K, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Modulatory effect of farnesyl pyrophosphate synthase (FDPS) rs2297480 polymorphism on the response to long-term amino-bisphosphonate treatment in postmenopausal osteoporosis. Current medical research and opinion. 2008. Marini Francesca, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Dairy products, polymorphisms in the vitamin D receptor gene and colorectal adenoma recurrence. International journal of cancer. Journal international du cancer. 2008. Hubner Richard A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Teriparatide or alendronate in glucocorticoid-induced osteoporosis. The New England journal of medicine. 2007. Saag Kenneth G, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Two single-nucleotide polymorphisms in the human vitamin D receptor promoter change protein-DNA complex formation and are associated with height and vitamin D status in adolescent girls. Human molecular genetics. 2005. d'Al├ęsio Arnold, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
BsmI vitamin D receptor genotypes influence the efficacy of antiresorptive treatments in postmenopausal osteoporotic women. A 1-year multicenter, randomized and controlled trial. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2005. Palomba Stefano, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Effectiveness of alendronate treatment in postmenopausal women with osteoporosis: relationship with BsmI vitamin D receptor genotypes. Clinical endocrinology. 2003. Palomba Stefano, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Two polymorphisms in the vitamin D receptor gene--association with bone mass and 5-year change in bone mass with or without hormone-replacement therapy in postmenopausal women: the Danish Osteoporosis Prevention Study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2002. Tofteng C L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
No major effect of estrogen receptor beta gene RsaI polymorphism on bone mineral density and response to alendronate therapy in postmenopausal osteoporosis. The Journal of steroid biochemistry and molecular biology. 2002. Arko Barbara, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
VDR genotype and response to etidronate therapy in late postmenopausal women. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 1999. Marc J, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0006-0925-31
DrugBank:
DB00630
PDB:
AHD
ChEBI:
2567
KEGG Compound:
C07752
PubChem Compound:
2088
PubChem Substance:
46507199
9954
Drugs Product Database (DPD):
2261715
BindingDB:
25313
ChemSpider:
2004
HET:
AHD
Therapeutic Targets Database:
DAP000182

Clinical Trials

These are trials that mention alendronate and are related to either pharmacogenetics or pharmacogenomics.

Common Searches

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.