Ticarcillin + Clavulanic acid

Intravenous
Bone and joint infections, Intra-abdominal infections, Peritonitis, Respiratory tract infections, Septicaemia, Skin and soft tissue infections, Urinary tract infections

Administer 3 g as loading dose followed by succeeding doses based on CrCl and type of dialysis as indicated below.
Patient on haemodialysis: 2 g 12 hourly or 3 g 24 hourly given via infusion or 1 g 6 hourly via IM inj; administer supplemental doses of 3 g via IV infusion after each dialysis session.

CrCl (mL/min)	Dosage
<10 (with hepatic impairment)	2 g 24 hourly given via IV infusion or 1 g 12 hourly via IM inj.
<10 or patient in peritoneal dialysis	2 g 12 hourly or 3 g 24 hourly given via infusion or 1 g 6 hourly via IM inj.
10-30	2 g 8 hourly or 3 g 12 hourly given via IV infusion.
30-60	2 g 4 hourly or 3 g 8 hourly given via IV infusion.
>60	3 g 4 hourly or 5 g 6 hourly given via IV infusion.

Reconstitute vial labelled as containing a combined potency of 1.6 g or 3.2 g with approx 5 mL or 10 mL of compatible diluent, respectively. Further dilute solution prior to infusion. Refer to detailed product guideline for further information.

Incompatible with proteinaceous fluids (e.g. protein hydrolysates), blood plasma, IV lipids, Na bicarbonate, and aminoglycosides.

History of hypersensitivity to ticarcillin, clavulanic acid, or other β-lactam antibiotics (e.g. cephalosporins, penicillins).

Patient with asthma, fluid and electrolyte imbalance, heart failure, history of seizure disorders. Renal and hepatic impairment. Children. Pregnancy and lactation.

Significant: Changes in LFTs, hypokalaemia, bleeding disorders (particularly in renally impaired patients); fungal or bacterial superinfection (prolonged use). Rarely, hypokalaemia.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea.
General disorders and administration site conditions: Local reactions (e.g. burning, induration, pain, swelling) and thrombophlebitis at the infusion site.
Hepatobiliary disorders: Very rarely, hepatitis and cholestatic jaundice.
Nervous system disorders: Rarely, convulsions (specifically in renally impaired patients or those receiving high doses).
Skin and subcutaneous tissue disorders: Rash, pruritus, urticaria.
Potentially Fatal: Anaphylaxis, pseudomembranous colitis and Clostridium difficile-associated diarrhoea.

Parenteral: B

Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Monitor serum electrolytes, bleeding time; renal, hepatic, and haematologic functions (periodically during long-term use). Observe for signs and symptoms of anaphylaxis during initial dose.

Symptoms: Gastrointestinal effects (e.g. nausea, vomiting, diarrhoea), disturbances of fluid and electrolyte balances; neuromuscular hyperirritability or convulsive seizures. Management: Symptomatic treatment. May initiate removal by haemodialysis.

Synergistic action with aminoglycosides against several organisms including Pseudomonas. May reduce the efficacy of hormonal oral contraceptives (e.g. estrogen).
Ticarcillin: Decreased renal tubular secretion with probenecid. May reduce the excretion of methotrexate which may increase the risk of toxicity.

May result in false-positive Coombs' test, and urinary proteins.

Description:
Mechanism of Action: Ticarcillin and clavulanic acid have distinctive activities of a broad-spectrum antibiotic and β-lactamase inhibitor.
Ticarcillin, a carboxypenicillin, has a broad-spectrum bactericidal activity against many Gram-positive and Gram-negative anaerobic and aerobic bacteria. It binds to 1 or more penicillin binding proteins (PBPs) which inhibits the final transpeptidation step of bacterial peptidoglycan cell wall synthesis, thus resulting in bacterial cell lysis and death.
Clavulanic acid is a β -lactam that has the ability to inhibit a wide range of β-lactamase enzymes usually found in microorganisms resistant to penicillins and cephalosporins. It protects ticarcillin from degradation by β-lactamase enzymes and extends the antibacterial spectrum of ticarcillin against many strains of β-lactamase-producing bacteria.
Pharmacokinetics:
Absorption: Time to peak plasma concentrations: Immediate (after completion of 30-minute infusion).
Distribution: Well distributed in body tissues and fluids. Crosses the placenta; enters breast milk (small amounts).
Ticarcillin: Distributed at low concentrations into CSF but may increase when meninges are inflamed. Plasma protein binding: 45-65%.
Clavulanic acid: Plasma protein binding: 22-30%.
Metabolism: Clavulanic acid: Metabolised in the liver.
Excretion: Ticarcillin: Via urine (approx 60-70% as unchanged drug). Elimination half-life: 66-72 minutes.
Clavulanic acid: Via urine (35-45% as unchanged drug). Elimination half-life: 66-90 minutes.

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 36921, Ticarcillin. https://pubchem.ncbi.nlm.nih.gov/compound/Ticarcillin. Accessed Nov. 25, 2021.

Source: National Center for Biotechnology Information. PubChem Database. Clavulanic acid, CID=5280980, https://pubchem.ncbi.nlm.nih.gov/compound/Clavulanic-acid (accessed on Apr. 28, 2020)

Store intact vials below 24°C.

Penicillin

J01CR03 - ticarcillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.

Anon. Ticarcillin and Clavulanate Potassium. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 04/11/2021.

Anon. Ticarcillin/Clavulanate. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 04/11/2021.

Buckingham R (ed). Clavulanic acid. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/11/2021.

Buckingham R (ed). Ticarcillin Monosodium. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/11/2021.

Timentin 0.8 g, 1.6 g, 3.2 g Powder for Solution for Infusion (Laboratoires Delbert). MHRA. https://products.mhra.gov.uk. Accessed 04/11/2021.