Pivmecillinam
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| Trade names | Selexid, Melysin, Coactabs, others |
| Other names | amdinocillin pivoxil (USANUS) |
| AHFS/Drugs | Micromedex Detailed Consumer Information |
| License data | |
| Routes of administration | By mouth |
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| Pharmacokineticdata | |
| Bioavailability | Low |
| Protein binding | 5 to 10% (as mecillinam) |
| Metabolism | Pivmecillinam ishydrolyzedto mecillinam |
| Eliminationhalf-life | 1 to 3 hours |
| Excretion | Kidneyand biliary, mostly as mecillinam |
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| CompTox Dashboard(EPA) | |
| ECHA InfoCard | 100.046.600 |
| Chemical and physical data | |
| Formula | C21H33N3O5S |
| Molar mass | 439.57g·mol−1 |
| 3D model (JSmol) | |
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Pivmecillinam(INN), oramdinocillin pivoxil(USAN), sold under the brand nameSelexidandPivyaamong others, is an orally activeprodrugofmecillinam,an extended-spectrumpenicillinantibiotic.Pivmecillinam is thepivaloyloxymethylesterof mecillinam.
The most common side effects includenauseaanddiarrhea.[2]
Medical uses
[edit]In the US, pivmecillinam isindicatedfor the treatment of female adults with uncomplicated urinary tract infections caused by susceptible isolates ofEscherichia coli,Proteus mirabilis,andStaphylococcus saprophyticus.[2]
Pivmecillinam is primarily active againstGram-negative bacteria,and is used primarily in the treatment of lowerurinary tract infections.In theNordic countries,it has been widely used in that indication since the 1970s.
Activity
[edit]Adverse effects
[edit]Theadverse effectprofile of pivmecillinam is similar to that of other penicillins. The most common side effects of mecillinam use arerashand gastrointestinal upset, includingnauseaandvomiting.[3][4]
Prodrugs that releasepivalate anionswhen broken down by the body — such as pivmecillinam,pivampicillinandcefditoren pivoxil— have long been known to deplete levels ofcarnitine.[5][6]This is not due to the drug itself, but to the pivalate anion, which is mostly removed from the body by forming a conjugate with carnitine. Although short-term use of these drugs can cause a marked decrease in blood levels of carnitine,[7]it is unlikely to be of clinical significance;[6]long-term use, however, appears problematic and is not recommended.[6][8][9]
History
[edit]The efficacy of pivmecillinam in treating females eighteen years of age or older with uncomplicated UTIs was assessed in three controlled clinical trials comparing different pivmecillinam dosing regimens toplacebo,to another oral antibacterial drug and toibuprofen(an anti-inflammatory drug).[2]The primary measure of efficacy for the three trials was the composite response rate, which included clinical cure (resolution of the symptoms of the uncomplicated UTI that were present in participants at trial entry and no new symptoms) and microbiological response (demonstration that the bacteria cultured from participants' urine at trial entry was reduced).[2]The composite response rate was assessed approximately 8 to 14 days after participants were enrolled into the studies.[2]In the clinical trial comparing pivmecillinam to placebo, 62% of the 137 participants who received pivmecillinam achieved the composite response compared to 10% of the 134 who received placebo.[2]In the clinical trial comparing pivmecillinam to another oral antibacterial drug, 72% of the 127 participants who received pivmecillinam achieved composite response compared to 76% of the 132 who received the comparator drug.[2]In the clinical trial comparing pivmecillinam to ibuprofen, 66% of the 105 participants who received pivmecillinam achieved composite response compared to 22% of the 119 who received ibuprofen.[2]
The USFood and Drug Administration(FDA) granted the application for pivmecillinampriority reviewand qualified infectious disease product designations.[2]The FDA granted the approval of Pivya to Utility Therapeutics Ltd.[2]
Research
[edit]Pivmecillinam has been proposed as thefirst-line drugof choice forempirical treatmentof acutecystitis.[3][10]It has also been used to treatparatyphoid feverand shigellosis.[11]
References
[edit]- ^"Selexid Summary of Product Characteristics (SmPC)".(emc).20 March 2024.Archivedfrom the original on 8 November 2023.Retrieved25 April2024.
- ^abcdefghijk"FDA Approves New Treatment for Uncomplicated Urinary Tract Infections".U.S.Food and Drug Administration(FDA)(Press release). 24 April 2024.Archivedfrom the original on 25 April 2024.Retrieved25 April2024.
This article incorporates text from this source, which is in thepublic domain.
- ^abNicolle LE (August 2000)."Pivmecillinam in the treatment of urinary tract infections".J Antimicrob Chemother.46(Suppl A): 35–39.doi:10.1093/jac/46.suppl_1.35.PMID10969050.
- ^"Selexid Tablets".electronic Medicines Compendium. 5 June 2008.[permanent dead link]Retrieved on 31 August 2008.
- ^Holme E, Greter J, Jacobson CE, et al. (August 1989). "Carnitine deficiency induced by pivampicillin and pivmecillinam therapy".Lancet.2(8661): 469–73.doi:10.1016/S0140-6736(89)92086-2.PMID2570185.
- ^abcBrass EP (December 2002)."Pivalate-generating prodrugs and carnitine homeostasis in man".Pharmacol Rev.54(4): 589–98.doi:10.1124/pr.54.4.589.PMID12429869.Archivedfrom the original on 14 December 2019.Retrieved29 June2009.
- ^Abrahamsson K, Holme E, Jodal U, Lindstedt S, Nordin I (June 1995). "Effect of short-term treatment with pivalic acid containing antibiotics on serum carnitine concentration—a risk irrespective of age".Biochem. Mol. Med.55(1): 77–9.doi:10.1006/bmme.1995.1036.PMID7551831.
- ^Holme E, Jodal U, Linstedt S, Nordin I (September 1992). "Effects of pivalic acid-containing prodrugs on carnitine homeostasis and on response to fasting in children".Scand J Clin Lab Invest.52(5): 361–72.doi:10.3109/00365519209088371.PMID1514015.
- ^Makino Y, Sugiura T, Ito T, Sugiyama N, Koyama N (September 2007). "Carnitine-associated encephalopathy caused by long-term treatment with an antibiotic containing pivalic acid".Pediatrics.120(3): e739–41.doi:10.1542/peds.2007-0339.PMID17724113.
- ^Graninger W (October 2003). "Pivmecillinam—therapy of choice for urinary tract infection".Int J Antimicrob Agents.22. Suppl 2: 73–8.doi:10.1016/S0924-8579(03)00235-8.PMID14527775.
- ^Tanphaichitra D, Srimuang S, Chiaprasittigul P, Menday P, Christensen OE (1984). "The combination of pivmecillinam and pivampicillin in the treatment of enteric fever".Infection.12(6): 381–3.doi:10.1007/BF01645219.PMID6569851.
