Ticarcillin Sodium

(BANM, rINNM)
Synonyms: BRL-2288; Natrii Ticarcillinum; Ticarcilina sódica; Ticarcillin Disodium cillinum natricum; Tikarcilin disodná sůl; Tikarcilin sodná sůl; Tikarcilino natrio druska; Tikarcillinnatrium; Tikarcillin-nátrium; Tikarsilliininatrium; Tykarcylina sodowa. Disodium (6R)-6-[2-carboxy-2(3-thienyl)acetamido]penicillanate.
Cyrillic synonym: Натрий Тикарциллин.

💊 Chemical information

Chemical formula: C15H14N2Na2O6S2 = 428.4.
CAS — 4697-14-7; 29457-07-6.
ATC — J01C A13.
ATC Vet — QJ01C A13.

Pharmacopoeias.

In Eur. and US.

Ph. Eur. 6.2

(Ticarcillin Sodium). A white or slightly yellow, hygroscopic powder. Freely soluble in water; soluble in methyl alcohol. A 5% solution in water has a pH of 5.5 to 7.5. Store in airtight containers at a temperature of 2° to 8°.

USP 31

(Ticarcillin Disodium). A white to pale yellow powder or solid. 1 mg of monograph substance has a potency equivalent to not less than 800 micrograms of ticarcillin, calculated on the anhydrous basis. Freely soluble in water. A 1% solution in water has a pH of 6.0 to 8.0. Store in airtight containers.

Incompatibility.

Ticarcillin sodium has been reported to be incompatible with aminoglycosides. 1. Swenson E, et al. Compatibility of ticarcillin disodium clavulanate potassium with commonly used intravenous solutions. Curr Ther Res 1990; 48: 385–94.

Stability.

References. 1. Zhang Y, Trissel LA. Stability of piperacillin and ticarcillin in AutoDose Infusion System bags. Ann Pharmacother 2001; 35: 1360–3.

💊 Adverse Effects and Precautions

As for Carbenicillin Sodium. Cholestatic jaundice and hepatitis have been reported when ticarcillin was used with clavulanic acid; the clavulanic acid component has been implicated. Ticarcillin should be given with caution to patients with renal impairment.

Breast feeding.

Although ticarcillin is distributed into breast milk in small amounts,1 no adverse effects have been seen in breast-fed infants and the American Academy of Pediatrics considers that it is usually compatible with breast feeding.2
1. von Kobyletzki D, et al. Ticarcillin serum and tissue concentrations in gynecology and obstetrics. Infection 1983; 11: 144–9
2. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001; 108: 776–89. Correction. ibid.; 1029. Also available at: http://aappolicy.aappublications.org/cgi/content/full/ pediatrics%3b108/3/776 (accessed 28/05/04)

Effects on the bladder.

The Australian Adverse Drug Reactions Advisory Committee had received 15 reports of haemorrhagic cystitis associated with ticarcillin or ticarcillin-clavulanic acid between 1980 and June 2002, mainly in paediatric cystic fibrosis patients.1 Almost all patients recovered quickly after the withdrawal of ticarcillin.
1. Adverse Drug Reactions Advisory Committee (ADRAC). Haemorrhagic cystitis with ticarcillin in cystic fibrosis patients. Aust Adverse Drug React Bull 2002; 21: 6–7. Also available at: http:// www.tga.gov.au/adr/aadrb/aadr0206.pdf (accessed 29/07/08)

Effects on the liver.

Cholestatic jaundice and hepatitis have been associated with combined preparations of a penicillin and clavulanic acid and 2 cases had been reported to the UK CSM with ticarcillin and clavulanic acid.1 It appeared that the clavulanic acid was probably responsible.
1. Committee on Safety of Medicines/Medicines Control Agency. Cholestatic jaundice with co-amoxiclav. Current Problems 1993; 19: 2. Available at: http://www.mhra.gov.uk/home/idcplg? IdcService=GET_FILE&dDocName=CON2024454& RevisionSelectionMethod=LatestReleased (accessed 22/07/08)

Sodium content.

Each g of ticarcillin sodium contains about 4.7 mmol of sodium.

💊 Interactions

💊 Antimicrobial Action

Ticarcillin is bactericidal and has a mode of action and range of activity similar to that of carbenicillin, but is reported to be 2 to 4 times more active against Pseudomonas aeruginosa. Combinations of ticarcillin and aminoglycosides have been shown to be synergistic in vitro against Ps. aeruginosa and Enterobacteriaceae. The activity of ticarcillin against organisms usually resistant because of the production of certain beta-lactamases is enhanced by clavulanic acid, a beta-lactamase inhibitor. Such organisms have included staphylococci, many Enterobacteriaceae, Haemophilus influenzae, and Bacteroides spp.; the activity of ticarcillin against Ps. aeruginosa is not enhanced by clavulanic acid. Resistance to ticarcillin with clavulanic acid has been reported. There is cross-resistance between carbenicillin and ticarcillin.
1. Pulverer G, et al. In-vitro activity of ticarcillin with and without clavulanic acid against clinical isolates of Gram-positive and Gram-negative bacteria. J Antimicrob Chemother 1986; 17 (suppl C): 1–5
2. Masterton RG, et al. Timentin resistance. Lancet 1987; ii: 975–6
3. Fass RJ, Prior RB. Comparative in vitro activities of piperacillintazobactam and ticarcillin-clavulanate. Antimicrob Agents Chemother 1989; 33: 1268–74
4. Kempers J, MacLaren DM. Piperacillin/tazobactam and ticarcillin/clavulanic acid against resistant Enterobacteriaceae. J Antimicrob Chemother 1990; 26: 598–9
5. Klepser ME, et al. Comparison of the bactericidal activities of piperacillin-tazobactam, ticarcillin-clavulanate, and ampicillinsulbactam against clinical isolates of Bacteroides fragilis, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa. Antimicrob Agents Chemother 1997; 41: 435–9.

💊 Pharmacokinetics

Ticarcillin is not absorbed from the gastrointestinal tract. After intramuscular injection of 1 g peak plasma concentrations in the range of 22 to 35 micrograms/mL are achieved after 0.5 to 1 hour. About 50% of ticarcillin in the circulation is bound to plasma proteins. A plasma half-life of 70 minutes has been reported. A shorter half-life in patients with cystic fibrosis (about 50 minutes in one study) has been attributed to increased renal and non-renal elimination. The half-life is prolonged in neonates and also in patients with renal impairment, especially if hepatic function is also impaired. A half-life of about 15 hours has been reported in severe renal impairment. Distribution of ticarcillin in the body is similar to that of carbenicillin. Relatively high concentrations have been reported in bile, but ticarcillin is excreted principally by glomerular filtration and tubular secretion. Concentrations of 2 to 4 mg/mL are achieved in the urine after the intramuscular injection of 1 or 2 g. Ticarcillin is metabolised to a limited extent. Up to 90% of a dose is excreted unchanged in the urine, mostly within 6 hours after a dose. Plasma concentrations are enhanced by probenecid. Ticarcillin is removed by haemodialysis and, to some extent, by peritoneal dialysis. Ticarcillin crosses the placenta and small amounts are distributed into breast milk. Ticarcillin with clavulanic acid. The pharmacokinetics of ticarcillin and clavulanic acid are broadly similar and neither appears to affect the other to any great extent.
1. Staniforth DH, et al. Pharmacokinetics of parenteral ticarcillin formulated with clavulanic acid: Timentin. Int J Clin Pharmacol Ther Toxicol 1986; 24: 123–9
2. Brogard JM, et al. Biliary elimination of ticarcillin plus clavulanic acid (Claventin ): experimental and clinical study. Int J Clin Pharmacol Ther Toxicol 1989; 27: 135–44
3. de Groot R, et al. Pharmacokinetics of ticarcillin in patients with cystic fibrosis: a controlled prospective study. Clin Pharmacol Ther 1990; 47: 73–8
4. Wang J-P, et al. Disposition of drugs in cystic fibrosis IV: mechanisms for enhanced renal clearance of ticarcillin. Clin Pharmacol Ther 1993; 54: 293–302
5. Burstein AH, et al. Ticarcillin-clavulanic acid pharmacokinetics in preterm neonates with presumed sepsis. Antimicrob Agents Chemother 1994; 38: 2024–8.

💊 Uses and Administration

Ticarcillin is a carboxypenicillin used in the treatment of severe Gram-negative infections, especially those due to Pseudomonas aeruginosa. Pseudomonal infections where ticarcillin is used include those in cystic fibrosis (respiratory-tract infections), immunocompromised patients (neutropenia), peritonitis, and septicaemia. Other infections that may be due to Ps. aeruginosa include bone and joint infections, meningitis, otitis media (chronic), skin infections. Ticarcillin is given to adults and children in a dose of 200 to 300 mg/kg daily by intravenous infusion in divided doses every 4 or 6 hours. In adults the use of probenecid 500 mg four times daily by mouth may produce higher and more prolonged plasma concentrations of ticarcillin, but caution is advised in patients with renal impairment. In the treatment of complicated urinary-tract infections, adults and children may be given a dose of ticarcillin 150 to 200 mg/kg daily by intravenous infusion in divided doses every 4 or 6 hours. In uncomplicated urinary-tract infections, the usual adult dose is ticarcillin 1 g every 6 hours intramuscularly or by slow intravenous injection. Children with uncomplicated urinary-tract infections may be given 50 to 100 mg/kg daily in divided doses every 6 or 8 hours. Not more than 2 g of ticarcillin should be injected intramuscularly into one site. In patients with cystic fibrosis, ticarcillin has been given by nebuliser in the management of respiratory-tract infections. Ticarcillin is often used with an aminoglycoside but the injections must be given separately because of possible incompatibility. Ticarcillin with clavulanic acid. Ticarcillin may be used with clavulanic acid, a beta-lactamase inhibitor, to widen its antibacterial spectrum to organisms usually resistant because of the production of beta-lactamases. This combination is given by intravenous infusion in a ratio of 15 or 30 parts of ticarcillin (as the sodium salt) to 1 part of clavulanic acid (as the potassium salt). Doses are according to the content of ticarcillin, and usual adult doses range from 9 to 18 g daily in 3 to 6 divided doses.

Administration in renal impairment.

Doses of ticarcillin may need to be reduced in patients with renal impairment. After an initial intravenous loading dose of 3 g, the intravenous maintenance dosage should be adjusted according to the patient’s creatinine clearance (CC):
CC 30 to 60 mL/minute: 2 g every 4 hours
CC 10 to 30 mL/minute: 2 g every 8 hours
CC less than 10 mL/minute: 2 g every 12 hours (or 1 g intramuscularly every 6 hours)
CC less than 10 mL/minute in presence of hepatic impairment: 2 g intravenously every 24 hours or 1 g intramuscularly every 12 hours
peritoneal dialysis patients: 3 g every 12 hours
haemodialysis patients: 2 g every 12 hours plus an additional dose of 3 g after each dialysis session

💊 Preparations

USP 31: Ticarcillin and Clavulanic Acid for Injection; Ticarcillin and Clavulanic Acid Injection; Ticarcillin for Injection.

Proprietary Preparations

Fr.: Ticarpen; Neth.: Ticarpen; Spain: Ticarpen; USA: Ticar. Multi-ingredient: Austral.: Timentin; Belg.: Timentin; Braz.: Timentin; Canad.: Timentin; Cz.: Timentin; Fr.: Claventin; Gr.: Timentin; Hong Kong: Timentin; India: Timentin; Irl.: Timentin†; Israel: Timentin; Ital.: Clavucar†; Timentin; Mex.: Timentin; Neth.: Timentin; NZ: Timentin; Philipp.: Timentin; Pol.: Timentin; Rus.: Timentin (Тиментин); Switz.: Timenten†; UK: Timentin; USA: Timentin.
Published May 08, 2019.