Fampridine

Structural formula
General
Non-proprietary name	Fampridine
other names	Pyridin-4-amine ( IUPAC ) 4-aminopyridine γ-aminopyridine p -aminopyridine 4-pyridylamine Dalfampridine (USAN) 4-AP Avitrol
Molecular formula	C 5 H 6 N 2
Brief description	beige solid with an unpleasant odor
External identifiers / databases
CAS number 504-24-5 EC number 207-987-9 ECHA InfoCard 100.007.262 PubChem 1727 ChemSpider 1664 DrugBank DB06637 Wikidata Q372539
Drug information
ATC code	N07 XX07
Mechanism of action	Potassium channel blockers
properties
Molar mass	94.12 g · mol -1
Physical state	firmly
density	1.26 g cm −3 (25 ° C)
Melting point	158.5 ° C
boiling point	274 ° C
solubility	soluble in water (83 g l −1 at 20 ° 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 danger H and P phrases H: 300-311-331-314-411 P: 301 + 330 + 331 + 310
Toxicological data	6.5 mg kg −1 ( LD 50 ,  rat ,  ip ) 21 mg kg −1 ( LD 50 ,  rat ,  oral ) 7 mg kg −1 ( LD 50 ,  mouse ,  ip ) 19 mg kg −1 ( LD 50 ,  mouse ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Fampridin (trade name Fampyra ^® ; manufacturer Biogen ) is a drug from the group of reversible potassium channel blockers, which is the first drug used in all forms of multiple sclerosis (MS) to improve the walking ability of adult MS patients (EDSS 4–7) becomes.

Chemically, the substance can be assigned to the aminopyridines .

Use as a medicine

Clinical information

Application areas (indications)

If MS is more advanced, people may develop walking difficulties that can be improved by physical therapy and certain, such as B. antispasmodic drugs can be treated. If the walking disability is of a certain severity, treatment with fampridine is an option. Fampridine has been approved in Germany since 2011 for patients with a higher degree of walking disability as a result of multiple sclerosis (MS) (grade 4–7 on the EDSS disability scale).

Type and duration of application

The recommended dose is one 10 mg tablet twice a day, 12 hours apart (one tablet in the morning and one tablet in the evening). Fampyra should not be taken more frequently or in higher doses than recommended.

Contraindications (contraindications)

Contraindications include hypersensitivity to fampridine, seizures , chronic kidney failure or simultaneous treatment with inhibitors of the organic cation transporter 2 (OTC2), e.g. B. cimetidine .

Adverse effects (side effects)

Fampridine is a drug with a narrow therapeutic window. Side effects include paresthesia , urinary tract infections , insomnia , dizziness , headache , nausea , asthenia , back pain , balance disorders and, in rare cases, seizures and atrial fibrillation .

Pharmacological properties

Mechanism of action (pharmacodynamics)

Fampridine is a potassium channel blocker. It acts on damaged nerves, where it prevents potassium ions from escaping from the nerve cells. It is believed that this allows the electrical impulses to travel further down the nerves to stimulate the muscles. This makes walking easier.

Absorption and distribution in the body (pharmacokinetics)

The Fampyra prolonged-release tablet delays the absorption of fampridine, which is noticeable as a slower increase to a lower peak concentration without any effect on the absorption rate.

AMNOG negotiations / reimbursement eligibility

The National Association of Statutory Health Insurance Funds and the company Biogen Idec have agreed on a reimbursement amount for Fampyra (fampridine). The reimbursement amount negotiated reflects the balance of interests between the statutory health insurance companies and Biogen Idec. With him, a negotiation result for a new drug with a non-drug ACT is available for the first time. For the prescribing doctor, this means in the case of fampridine that it can be prescribed in combination with or without physiotherapy and is reimbursable if used appropriately in the approved area of ​​application.

Studies

• After subtracting the response rate under placebo , around 30% of the patients treated with fampridine in the approval studies benefited from improved walking ability: around 20% of the patients were able to cover a certain walking distance 10 to 20% faster and around 10% of the patients improved Walking speed by 20% and more. The patients in these studies were treated with fampridine for a maximum of 14 weeks.
• An interim evaluation of the ongoing ENABLE study (quality of life) showed a significant improvement in the subjective assessment of health-related quality of life through the increase in walking ability with fampridine.
• Another interim evaluation of the ongoing ENABLE study showed that the effect of fampridine on improving walking ability and the associated health-related quality of life persisted for 48 weeks.

History

Fampridine was first synthesized in 1902 by the Karlsruhe chemist Rudolf Camps . The international non-proprietary name (INN) fampridine was granted in 1995. In contrast to this, the non-proprietary name Dalfampridine (USAN) was introduced in the USA in 2010 .

2010 Manufacturer Acorda received an authorization for a Fampridine-containing sustained release medicines to support the treatment of multiple sclerosis . However, a corresponding application for the EU was initially rejected at the beginning of 2011 due to an inadequate benefit-risk ratio . After an objection, Acorda's licensee Biogen received approval in mid-2011 , subject to the condition that further studies be carried out. A decision by the Swiss authorities is still pending.

Parts of this article seem out of date as of 2012 .
Please help to research and insert the missing information .

Trade names

The trade name for the finished medicinal product in the EU and Switzerland is Fampyra and in the USA Ampyra . Fampridine can by even after prescribing doctor in pharmacies to recipe drugs are processed.

Use outside of human medicine

• 4-aminopyridine is u. a. used for the production of 4-halopyridines or the active ingredient pinacidil. 4- (Dimethylamino) pyridine (DMAP), a derivative of fampridine that is dimethylated on the amino group, is a catalyst that is frequently used in preparative chemistry. Fampridine is domestic and farm animals in combination with yohimbine as Aufwachbeschleuniger after Xylazine - and ketamine - anesthesia ( " Hella Brunner mixture used").
• 4-aminopyridine is used as a bird poison and repellent under the trade name Avitrol . 4-aminopyridine drives away birds by paralyzing the animals that have ingested the poison bait and screaming for distress, after which the rest of the flock is hoped and scared.

Web links

• Public Assessment Report (EPAR) of the European Medicines Agency (EMA) for: Fampridine

Individual evidence

1. ↑ ^{a b c d e f} Entry on 4-aminopyridine in the GESTIS substance database of the IFA , accessed on January 8, 2020(JavaScript required) .
2. ↑ Data sheet 4-aminopyridine from Sigma-Aldrich , accessed on January 27, 2020 ( PDF ).
3. ↑ ^{a b c d} Entry on fampridine in the ChemIDplus database of the United States National Library of Medicine (NLM) .
4. ↑ ^{a b c d e} Fampyra specialist information. Red list, specialist information service; accessed on February 27, 2014.
5. ↑ T. Pickett, R. Enns: Atypical presentation of 4-aminopyridine overdose. In: Ann Emer Med. 27, 1996, pp. 382-385. PMID 8599505 .
6. ↑ N. Johnson, M. Morgan: An unusual case of 4-aminopyridine toxicity. In: J Emer Med. 30, 2006, pp. 175-177. PMID 16567254 .
7. ↑ Summary of the EPAR for the public. (PDF) Website of the European Health Authority (EMA); accessed on February 27, 2014.
8. ↑ AMNOG negotiations for MS therapeutic agent successfully concluded , joint press release by National Association of Statutory Health Insurance Funds and Biogen Idec from March 1, 2013, accessed on February 27, 2014.
9. ^ AD Goodman, TR Brown, LB Krupp et al. a .: Sustained-release oral fampridine in multiple sclerosis: a randomized, double-blind, controlled trial. In: The Lancet . 373, 2009, pp. 732-738. PMID 19249634 .
10. ^ AD Goodman, TR Brown, KR Edwards et al. a .: A phase 3 trial of extended release oral dalfampridine in multiple sclerosis. In: Ann Neurol . 68, 2010, pp. 494-502. PMID 20976768 .
11. ↑ Richard Macdonnell, Guy Nagels, Per Solberg Sorensen, David Laplaud, Carlo Pozzilli, Ana Silva, Richard Nicholas, Mathias Niedhammer, Julia Gaebler, Sonalee Agarwal and James Potts: Change in Quality of Life Outcomes with Prolonged-Release Fampridine Treatment: Interim Analysis of the ENABLE Study . In: Neurology . tape 80 , supp. 7, 2013, p. P03.218-P03.218 ( neurology.org ).
12. ^ R. Macdonell: Long-term prolonged-release fampridine treatment and health-related quality of life outcomes: 12-month analysis of the ENABLE study. In: ECTRIMS Online Library , 3 Oct 2013, 34145; accessed on February 27, 2014.
13. ↑ R. Camps: About some ureas, thioureas and urethanes of pyridine. In: Arch Pharm . 240, 1902, pp. 345-365. doi: 10.1002 / ardp.19022400505 .
14. ^ Recommended International Nonproprietary Names for Pharmaceutical Substances. INN List 35 . In: WHO Drug Information . tape 9 , no. 3 , 1995, p. 174 ( who.int [PDF]).
15. ↑ Raymond Lamore III, Elsen Jacob, Susan C. Jacob, Olga Hilas: Dalfampridine (Ampyra) . In: Pharmacy and Therapeutics . tape 35 , no. 12 , 2010, p. 665-669 , PMC 3008376 (free full text).
16. ↑ US Food and Drug Administration (January 22, 2010): FDA Approves Ampyra to Improve Walking in Adults with Multiple Sclerosis. Retrieved January 26, 2010.
17. ^ Refusal of the marketing authorization for Fampyra (fampridine) . (PDF; 51 kB) European Medicines Agency, January 20, 2011; Retrieved January 30, 2011.
18. ↑ Fampyra: EPAR - Summary for the public . European Medicines Agency (EMA); Retrieved December 1, 2011.
19. ↑ “New Medicines” Fampyra ^® To improve the walking ability of adult patients with multiple sclerosis (MS) with walking difficulties (EDSS 4–7) . (PDF; 318 kB) Drugs Commission of the German Medical Association (AkdÄ); Retrieved December 1, 2011.
20. ↑ Biogen Idec receives conditional marketing approval for FAMPYRA® in the European Union to improve the walking ability of adult multiple sclerosis patients . Businesswire, July 25, 2011; Retrieved July 26, 2011.
21. ↑ Michael Linnebank: Fampridine to improve walking ability . In: Forte . No. 4 , November 2012, ZDB -ID 2412672-X ( multiplesklerose.ch [PDF]).
22. ↑ © Copyright Swissmedic 2019: Fampyra®, prolonged-release tablets (Fampridinum). Retrieved December 11, 2019 . 
23. ^ Federal Association of German Pharmacists' Associations: New Formulation Form. Recipe information: 3,4-diaminopyridine and 4-aminopyridine. Govi, Eschborn 2009.
24. ↑ Wolfgang Löscher, Fritz Rupert Ungemach, Reinhard Kroker: Pharmacotherapy for pets and farm animals. Thieme, Stuttgart 2006, ISBN 3-8304-4160-6 , p. 101.
25. ^ EXTOXNET: Pesticide Information Profile .

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !