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Pivmecillinam
Clinical data
Trade names	Selexid, Melysin, Coactabs, others
Other names	amdinocillin pivoxil (USAN US)
AHFS/Drugs.com	Monograph
License data	US DailyMed: Amdinocillin pivoxil;
Routes of; administration	By mouth
ATC code	J01CA08 (WHO) ;
Legal status
Legal status	UK: POM (Prescription only); US: ℞-only; In general: ℞ (Prescription only);
Pharmacokinetic data
Bioavailability	Low
Protein binding	5 to 10% (as mecillinam)
Metabolism	Pivmecillinam is hydrolyzed to mecillinam
Elimination half-life	1 to 3 hours
Excretion	Kidney and biliary, mostly as mecillinam
Identifiers
	IUPAC name 2,2-dimethylpropanoyloxymethyl (2S,5R,6R)-6-[(azepan-1-ylmethylene)amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate;
CAS Number	32886-97-8 ; 32887-03-9;
PubChem CID	115163; 115162;
DrugBank	DB01605 ; DBSALT001943;
ChemSpider	16735658 ; 19978599;
UNII	1WAM1OQ30B; 48FX7N21H2;
KEGG	D02889 ; D01499;
ChEMBL	ChEMBL1650818 ;
CompTox Dashboard (EPA)	DTXSID7048538 ;
ECHA InfoCard	100.046.600
Chemical and physical data
Formula	C21H33N3O5S
Molar mass	439.57 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1(C(N2C(S1)C(C2=O)N=CN3CCCCCC3)C(=O)OCOC(=O)C(C)(C)C)C;
	InChI InChI=1S/C21H33N3O5S/c1-20(2,3)19(27)29-13-28-18(26)15-21(4,5)30-17-14(16(25)24(15)17)22-12-23-10-8-6-7-9-11-23/h12,14-15,17H,6-11,13H2,1-5H3/t14-,15+,17-/m1/s1; Key:NPGNOVNWUSPMDP-HLLBOEOZSA-N; ; InChI=1S/C21H33N3O5S.ClH/c1-20(2,3)19(27)29-13-28-18(26)15-21(4,5)30-17-14(16(25)24(15)17)22-12-23-10-8-6-7-9-11-23;/h12,14-15,17H,6-11,13H2,1-5H3;1H/t14-,15+,17-;/m1./s1; Key:UHPXMYLONAGUPC-WKLLBTDKSA-N;
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Pivmecillinam (INN), or amdinocillin pivoxil (USAN), sold under the brand name Selexid and Pivya among others, is an orally active prodrug of mecillinam, an extended-spectrum penicillin antibiotic. Pivmecillinam is the pivaloyloxymethyl ester of mecillinam.

The most common side effects include nausea and diarrhea.^[3]

Medical uses

In the US, pivmecillinam is indicated for the treatment of female adults with uncomplicated urinary tract infections caused by susceptible isolates of Escherichia coli, Proteus mirabilis, and Staphylococcus saprophyticus.^[3]

Pivmecillinam is primarily active against Gram-negative bacteria, and is used primarily in the treatment of lower urinary tract infections. In the Nordic countries, it has been widely used in that indication since the 1970s.

Activity

Adverse effects

The adverse effect profile of pivmecillinam is similar to that of other penicillins. The most common side effects of mecillinam use are rash and gastrointestinal upset, including nausea and vomiting.^[4]^[5]

Prodrugs that release pivalate anions when broken down by the body — such as pivmecillinam, pivampicillin and cefditoren pivoxil — have long been known to deplete levels of carnitine.^[6]^[7] 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,^[8] it is unlikely to be of clinical significance;^[7] long-term use, however, appears problematic and is not recommended.^[7]^[9]^[10]

History

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 to placebo, to another oral antibacterial drug and to ibuprofen (an anti-inflammatory drug).^[3] 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).^[3] The composite response rate was assessed approximately 8 to 14 days after participants were enrolled into the studies.^[3] 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.^[3] 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.^[3] 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.^[3]

The US Food and Drug Administration (FDA) granted the application for pivmecillinam priority review and qualified infectious disease product designations.^[3] The FDA granted the approval of Pivya to Utility Therapeutics Ltd.^[3]

Research

Pivmecillinam has been proposed as the first-line drug of choice for empirical treatment of acute cystitis.^[4]^[11] It has also been used to treat paratyphoid fever and shigellosis.^[12]

References

^ "Selexid Summary of Product Characteristics (SmPC)". (emc). 20 March 2024. Archived from the original on 8 November 2023. Retrieved 25 April 2024.
^ https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/216483s000lbl.pdf
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k "FDA Approves New Treatment for Uncomplicated Urinary Tract Infections". U.S. Food and Drug Administration (FDA) (Press release). 24 April 2024. Archived from the original on 25 April 2024. Retrieved 25 April 2024. This article incorporates text from this source, which is in the public domain.
^ ^a ^b Nicolle 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. PMID 10969050.
^ "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. PMID 2570185.
^ ^a ^b ^c Brass EP (December 2002). "Pivalate-generating prodrugs and carnitine homeostasis in man". Pharmacol Rev. 54 (4): 589–98. doi:10.1124/pr.54.4.589. PMID 12429869. Archived from the original on 14 December 2019. Retrieved 29 June 2009.
^ 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. PMID 7551831.
^ 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. PMID 1514015.
^ 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. PMID 17724113.
^ 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. PMID 14527775.
^ 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. PMID 6569851.