Alendronic acid

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Structural formula
Structure of alendronic acid
General
Non-proprietary name Alendronic acid
other names
  • (4-Amino-1-hydroxybutylidene) diphosphonic acid
  • Alendronate
Molecular formula C 4 H 13 NO 7 P 2
External identifiers / databases
CAS number
  • 66376-36-1 alendronic acid
  • 121268-17-5 (sodium alendronate, monosodium alendronate trihydrate)
EC number 613-929-7
ECHA InfoCard 100.128.415
PubChem 2088
ChemSpider 2004
DrugBank DB00630
Wikidata Q420057
Drug information
ATC code

M05 BA04

Drug class

Bisphosphonates

properties
Molar mass 249.10 g · mol -1
Physical state

firmly

Melting point

234 ° C

pK s value

2.72 (25 ° C)

safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
07 - Warning

Caution

H and P phrases H: 302
P: no P-phrases
Toxicological data

552 mg kg −1 ( LD 50 ,  rat ,  oral )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Alendronic acid is a drug that is used to treat osteoporosis . Chemically, alendronic acid belongs to the group of bisphosphonates ; Its monosodium salt (sodium alendronate) is used medicinally . The salts of alendronic acid are called alendronates; in everyday clinical practice both terms are often used synonymously.

pharmacology

effect

Like the other representatives of bisphosphonates, alendronic acid, with its PCP structure similar to that of pyrophosphate, inhibits various proteins in osteoclasts . This inhibits their ability to resorb bone substance. The effect is based on the inhibition of cholesterol synthesis . According to Galeazzi and Gysling, the drug acts on both the osteoclasts and the osteoblasts. But the increase in bone mass predominates.

Pharmacokinetics

As with other oral bisphosphonates, the active ingredient is only absorbed intestinally to a small extent (approx. 0.5–1%). About 50% of the absorbed active ingredient is incorporated into the bone, the other half is eliminated almost completely unchanged via the kidneys within 6 hours . Presumably the preparation built into the bone substance is excreted with a half-life of about 10 years. Alendronate is contraindicated in renal insufficiency; massive storage of alendronic acid can occur.

Indications

Alendronic acid is approved in the strengths of 10 mg daily and 70 mg weekly for the treatment of postmenopausal osteoporosis in order to reduce the risk of vertebral and hip fractures. Further approvals exist for the 10 mg tablet for corticoid- induced osteoporosis and osteoporosis in men. In clinical studies, administration of alendronate has shown a positive effect on bone density and a reduction in the risk of bone fractures . Despite these good results, it must be pointed out that not all patients benefited from this therapy and that, according to a study from 1998, at least 1,000 osteoporotic women must receive alendronic acid for 3 years in order to avoid 27 fractures. A meta-analysis from 2004 shows a 55% reduction in hip fractures in osteoporosis.

In addition, the preparation is also prescribed for osteodystrophia deformans in the USA . However, alendronic acid in the recommended concentration of around 40 mg per day causes undesirable effects relatively frequently.

Contraindications

Like other bisphosphonates, alendronic acid must not be used in the case of chronic kidney failure or acute infections in the digestive tract . Other diseases, especially in the upper gastrointestinal tract, are contraindications to the administration of alendronic acid.

Due to a lack of data on the effect in pregnancy, breastfeeding and childhood, pregnant or breastfeeding women and children should not take the preparation.

Precautions

Like other bisphosphonates, alendronic acid can cause local irritation of the mucous membrane of the upper gastrointestinal tract . Side effects of the esophagus - such as inflammation, ulceration, and esophageal erosion, rarely followed by strictures or perforations - have been reported during therapy with alendronic acid. In some cases, these side effects were severe and required hospitalization. Physicians should therefore be vigilant for signs or symptoms of a possible esophageal reaction and patients should be instructed to discontinue alendronic acid and contact their doctor if swallowing difficulties, swallowing pain, sternum pain, or worsening heartburn worsen . The risk of adverse effects on the esophagus appears to be greater in patients who do not take alendronic acid according to the instructions or who continue to take alendronic acid after they experience symptoms of the esophagus. For efficacy and tolerability, it is therefore particularly important that the dosage instructions are explained to the patient and that they have understood them. Due to the possible irritation of the mucous membrane of the gastrointestinal tract and the potential for worsening an existing disease, alendronic acid should only be given with caution in the presence of problems in the upper gastrointestinal tract - such as swallowing difficulties, esophageal diseases, gastric mucosal inflammation , duodenitis or ulcers. In chronic kidney failure with a creatinine clearance of <30 ml / min, regular controls of kidney function, blood count and serum phosphate level are indicated. In addition to hormone deficiency, age, and glucocorticoid treatment , other causes of osteoporosis should also be considered. A hypocalcemia must be corrected with alendronate before initiation of treatment. Therefore, an adequate calcium intake must be ensured in these patients. Other mineral metabolism disorders (such as vitamin D deficiency) should also be treated.

Side effects

There are numerous possible side effects of treatment with alendronic acid. They occur particularly in the gastrointestinal tract and in the musculoskeletal system. At higher doses, they resemble the general side effects of bisphosphonates , also in the dental field. The following are the most common side effects:

Gastrointestinal tract
Esophagus
Musculature and skeletal system
Nervous system
Other symptoms

application

Alendronic acid requires a prescription and is given once a week in the form of a tablet (alendronate amount 70 mg) or once a day (10 mg alendronate). Since the active ingredient forms insoluble complexes with calcium and other mineral salts, it is necessary to take the drug alone at least 30 minutes before eating, preferably in the morning with sufficient liquid (about 200 ml of tap water, no fruit juice, no milk), in an upright position. Subsequently, do not assume a lying posture for about 30 minutes, as undesirable effects on the gullet ( esophagus ) can occur. One recommendation is to take the drug before washing in the morning.

Chemical properties

Alendronic acid belongs to the group of bisphosphonates. It is a white crystalline powder and decomposes at a temperature of 230 ° C. The derived sodium alendronate (C 4 H 12 NNaO 7 P 2 · 3H 2 O, monosodium salt ) has similar properties and the CAS number 121268-17-5.

Trade names

Monopreparations

Fosamax (D, CH), Tevanate (D), numerous generics (D, CH)

Combination preparations

Fosavance (D, CH), Tevabone (D)

Web links

Wiktionary: alendronic acid  - explanations of meanings, word origins, synonyms, translations

Individual evidence

  1. ↑ a b Entry on alendronic acid in the ChemIDplus database of the United States National Library of Medicine (NLM)
  2. ↑ a b c data sheet Alendronate sodium trihydrate from Sigma-Aldrich , accessed on March 20, 2011 ( PDF ).
  3. ↑ a b c Michael Freissmuth, Stefan Böhm: Pharmacology and Toxicology From the Molecular Basics to Pharmacotherapy . Springer-Verlag, 2012, ISBN 978-3-642-12354-2 , pp. 594 ( limited preview in Google Book search).
  4. ↑ a b c d e G.K. Stalla: Endocrinology and Metabolic Diseases Therapy Dictionary . Springer-Verlag, 2007, ISBN 978-3-540-30033-5 , pp. 42 ( limited preview in Google Book search).
  5. ↑ der-arzneimittelbrief.de: Therapy with bisphosphonates for bone diseases. Effects, indications, side effects (part 2), AMB 1998, 32, 49 , accessed on May 7, 2016
  6. ^ Socrates E. Papapoulos, Sara A. Quandt, Uri A. Liberman, Marc C. Hochberg, Desmond E. Thompson: Meta-analysis of the efficacy of alendronate for the prevention of hip fractures in postmenopausal women. In: Osteoporosis International. 16, 2005, p. 468, doi : 10.1007 / s00198-004-1725-z .
  7. ↑ Lippincott: Nursing 2015 Drug Handbook . Lippincott Williams & Wilkins, 2014, ISBN 978-1-4698-3744-4 , pp. 95 ( limited preview in Google Book search).
This text is based in whole or in part on the entry alendronic acid in Flexikon , a wiki from DocCheck . The takeover took place on July 21, 2004 under the then valid GNU license for free documentation .