Teicoplanin

Teicoplanin is an antibiotic agent belonging to the pharmacological class of Glycopeptide Antibiotics.

Teicoplanin has been approved to relieve symptoms and also for the treatment and maintenance of Complicated skin and soft tissue infections, Bone and joint infections, Hospital-acquired pneumonia, Community-acquired pneumonia, Complicated urinary tract infections, Infective endocarditis, Peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD), Bacteremia that occurs in association with any of the aforementioned indications.

Teicoplanin, when administered orally, does not undergo significant systemic absorption in the gastrointestinal tract. Instead, approximately 40% of the administered dose is excreted in the feces with microbiological activity. Intravenous administration of teicoplanin at a dose of 3-6 mg/kg results in a biphasic distribution pattern, with a rapid distribution phase (half-life of approximately 0.3 hours) followed by a more prolonged phase (half-life of approximately 3 hours). The elimination half-life is approximately 150 hours, enabling once-daily dosing. However, without a loading dose, it takes 2-3 weeks to reach a steady-state plasma concentration of 14 mg/L. By administering a loading dose of 6 mg/kg every twelve hours, a predicted trough plasma concentration of 10 mg/L can be achieved by the fourth dose. Teicoplanin readily distributes into various tissues, including skin, blister fluid, myocardium, pulmonary tissue, pleural fluid, bone, and synovial fluid, but it does not readily cross the blood-brain barrier to reach cerebrospinal fluid. It exhibits weak affinity for plasma proteins, with approximately 90-95% binding. The steady-state volume of distribution ranges from 0.94 to 1.4 L/kg. Teicoplanin undergoes minor metabolic transformation (about 3%), and approximately 80% of the administered drug is eliminated in the urine. Renal clearance ranges from 10.4 to 12.1 mL/h/kg after intravenous administration of 3-6 mg/kg.

The common side effects involved in using Teicoplanin are Nausea, Vomiting, Diarrhea, Abdominal pain, Gastrointestinal discomfort, Skin rash, Itching, Hives (urticaria), Injection site pain, Injection site redness, Injection site swelling, and Allergic reactions.

Teicoplanin is available in the form of Injections.

Teicoplanin is approved in Germany, Japan, Malaysia, India, the U.K., the U.S., and China.

Teicoplanin belongs to the pharmacological class of Glycopeptide Antibiotics

Teicoplanin works by blocking the process of peptidoglycan polymerization, leading to the inhibition of bacterial cell wall formation and ultimately causing the death of the bacteria.

Teicoplanin has been approved to relieve symptoms and also for the treatment and maintenance of Complicated skin and soft tissue infections, Bone and joint infections, Hospital-acquired pneumonia, Community-acquired pneumonia, Complicated urinary tract infections, Infective endocarditis, Peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD), Bacteremia that occurs in association with any of the aforementioned indications.

Following the administration of six consecutive intramuscular doses of 200 mg, the peak concentration of teicoplanin (Cmax) reaches an average of 12.1 mg/L within 2 hours.

After intravenous administration, teicoplanin reaches peak plasma concentrations within 1 to 2 hours. Teicoplanin has a prolonged half-life, which allows for once-daily dosing. The elimination half-life of teicoplanin is approximately 100 to 170 hours.

Teicoplanin is found to be available in the form of Injections.

Teicoplanin can be used in the following treatment:

• Complicated skin and soft tissue infections
• Bone and joint infections
• Hospital-acquired pneumonia
• Community-acquired pneumonia
• Complicated urinary tract infections
• Infective endocarditis
• Peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD)
• Bacteremia that occurs in association with any of the aforementioned indications.

Teicoplanin is approved for use in the following clinical indications:

• Complicated skin and soft tissue infections
• Bone and joint infections
• Hospital-acquired pneumonia
• Community-acquired pneumonia
• Complicated urinary tract infections
• Infective endocarditis
• Peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD)
• Bacteremia that occurs in association with any of the aforementioned indications

• Complicated skin and soft tissue infections: The recommended dosage strength of teicoplanin may vary depending on the severity of the infection and other factors. Typical dosages range from 400 mg to 800 mg, administered intravenously once a day or in divided doses.
• Bone and joint infections: The recommended dosage strength for teicoplanin in the treatment of bone and joint infections is typically 400 mg to 800 mg, administered intravenously once a day or in divided doses.
• Hospital-acquired pneumonia: The recommended dosage strength for teicoplanin in the treatment of hospital-acquired pneumonia is typically 400 mg to 800 mg, administered intravenously once a day or in divided doses.
• Community-acquired pneumonia: The recommended dosage strength for teicoplanin in the treatment of community-acquired pneumonia is typically 400 mg to 800 mg, administered intravenously once a day or in divided doses.
• Complicated urinary tract infections: The recommended dosage strength for teicoplanin in the treatment of complicated urinary tract infections is typically 400 mg to 800 mg, administered intravenously once a day or in divided doses.
• Infective endocarditis: The recommended dosage strength for teicoplanin in the treatment of infective endocarditis is typically 400 mg to 800 mg, administered intravenously once a day or in divided doses.
• Peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD): The recommended dosage strength of teicoplanin for peritonitis associated with CAPD may vary. Typical dosages range from 400 mg to 800 mg, administered intravenously once a day or in divided doses.
• Bacteremia associated with the aforementioned indications: The recommended dosage strength of teicoplanin for bacteremia occurring in association with the indicated conditions may vary. Typical dosages range from 400 mg to 800 mg, administered intravenously once a day or in divided doses.

Injection: 200 mg, 400mg.

There are no specific dietary restrictions associated with the use of Teicoplanin.

Teicoplanin may be contraindicated under the following conditions:

• Teicoplanin should not be used in individuals with a known hypersensitivity or allergic reaction to the drug Teicoplanin.

Hypersensitivity Reactions:

• Serious and life-threatening hypersensitivity reactions, including anaphylactic shock, have been reported with teicoplanin.
• Immediate discontinuation of treatment and initiation of emergency measures are necessary if an allergic reaction to teicoplanin occurs.
• Caution should be exercised when administering teicoplanin to patients with known hypersensitivity to vancomycin, as cross-reactivity and fatal anaphylactic shock may occur.
• A history of "red man syndrome" with vancomycin does not contraindicate the use of teicoplanin.

Infusion-Related Reactions:

• In rare cases, infusion-related reactions such as red man syndrome, characterized by symptoms like pruritus, urticaria, erythema, angioneurotic edema, tachycardia, hypotension, and dyspnea, have been observed, even with the first dose.
• Slowing down or stopping the infusion can help alleviate these reactions.
• Infusion-related reactions can be minimized by administering the daily dose of teicoplanin over a 30-minute period rather than as a bolus injection.

Severe Bullous Reactions:

• Life-threatening cutaneous reactions, including Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN), have been reported with the use of teicoplanin.
• Immediate discontinuation of teicoplanin treatment is necessary if symptoms or signs of SJS or TEN, such as progressive skin rash with blisters or mucosal lesions, are present.

The Spectrum of Antibacterial Activity:

• Teicoplanin has a limited spectrum of antibacterial activity, primarily targeting Gram-positive bacteria.
• It may not be suitable as a single agent for treating certain infections unless the pathogen is known to be susceptible to teicoplanin or there is a high suspicion that teicoplanin would be effective.
• The decision to use teicoplanin should consider its bacterial activity, safety profile, and the suitability of standard antibacterial therapy for the individual patient.
• Teicoplanin is typically reserved for severe infections when standard antibacterial agents are deemed unsuitable.

Loading Dose Regimen:

• The safety of teicoplanin doses of 12 mg/kg body weight administered twice a day is limited, and close monitoring of adverse reactions is necessary.
• Alongside recommended periodic hematological examinations, monitoring of blood creatinine levels is also advised under this dosing regimen.
• Teicoplanin should not be administered intraventricularly.

Thrombocytopenia:

• Thrombocytopenia (reduced platelet count) has been reported with teicoplanin use.
• Regular hematological examinations, including complete blood cell count, are recommended during treatment.

Nephrotoxicity:

• Renal failure has been reported in patients treated with teicoplanin, especially in those with renal insufficiency or receiving other nephrotoxic medications.
• Close monitoring, including auditory tests, is necessary in such patients.

Ototoxicity:

• Teicoplanin, like other glycopeptides, has been associated with ototoxicity, including hearing impairment and tinnitus.
• Patients should be carefully evaluated and monitored, particularly during prolonged treatment and in those with renal insufficiency.
• Close monitoring is also required when teicoplanin is used concomitantly with other neurotoxic/ototoxic medications.
• Regular hematological, liver, and kidney function tests are recommended for patients receiving teicoplanin and concomitant ototoxic and/or nephrotoxic medications.

Superinfection:

• Prolonged use of teicoplanin may lead to the overgrowth of non-susceptible organisms.

While there is no specific food interaction between Teicoplanin and alcohol, it's generally recommended to avoid alcohol when taking any antibiotic medication. Alcohol can interfere with the effectiveness of the medication and may also exacerbate certain side effects.

The excretion of teicoplanin in human milk is not currently known. There is also a lack of information regarding the excretion of teicoplanin in animal milk. Therefore, when considering the use of teicoplanin while breastfeeding, a careful decision should be made by weighing the benefits of breastfeeding for the child against the benefits of teicoplanin therapy for the mother. It is important to assess the overall situation and make an informed decision regarding the continuation or discontinuation of either breastfeeding or teicoplanin therapy.

Pregnancy Category B

Unless a physician determines that the potential benefits outweigh any potential risks, teicoplanin should not be used during confirmed or presumed pregnancy. Studies conducted on animals regarding reproductive effects have not provided evidence of teratogenic effects.

No food warning has been identified

The adverse reactions related to Teicoplanin can be categorized as follows:

Hypersensitivity:

• Rash
• Pruritus (itching)
• Fever
• Rigors (shivering or trembling)
• Bronchospasm (constriction of the airways)
• Anaphylactic reactions
• Anaphylactic shock
• Urticaria (hives)
• Angioedema (swelling)
• Rare cases of exfoliative dermatitis
• Rare cases of toxic epidermal necrolysis
• Rare cases of erythema multiforme, including Stevens-Johnson syndrome

Infusion-related events:

• Erythema or flushing of the upper body (rare)
• Occurrence without prior teicoplanin exposure history
• Events not recurring with slowed infusion rate or decreased concentration
• No specificity to any concentration or infusion rate

Gastrointestinal:

• Nausea
• Vomiting
• Diarrhea

Blood:

• Rare cases of reversible agranulocytosis (low white blood cell count)
• Leucopenia (low white blood cell count)
• Neutropenia (low neutrophil count)
• Thrombocytopenia (low platelet count)
• Eosinophilia (increased eosinophil count)

Liver function:

• Increases in serum transaminases
• Increases in serum alkaline phosphatase

Renal function:

• Elevations of serum creatinine
• Renal failure

Central nervous system:

• Dizziness
• Headache
• Seizures (with intraventricular use)

Auditory/vestibular:

• Hearing loss
• Tinnitus (ringing in the ears)
• Vestibular disorders

Other:

• Superinfection (overgrowth of non-susceptible organisms)

No specific interaction studies have been conducted.

Teicoplanin and aminoglycoside solutions should not be mixed for injection due to incompatibility. However, they can be safely used together in dialysis fluid for the treatment of CAPD-related peritonitis.

Caution should be exercised when using teicoplanin in conjunction with or sequentially with other medications known to have nephrotoxic or ototoxic effects, such as aminoglycosides, colistin, amphotericin B, ciclosporin, cisplatin, furosemide, and ethacrynic acid (refer to section 4.4). Nevertheless, there is no evidence of synergistic toxicity when combining these medications with teicoplanin.

Clinical studies have shown that teicoplanin can be safely administered to patients already receiving various medications, including other antibiotics, antihypertensives, anesthetic agents, cardiac medicinal products, and antidiabetic agents, without any adverse interactions being observed.

The following are the side effects involving Teicoplanin:

• Nausea
• Vomiting
• Diarrhea
• Swelling
• Rashes
• Fever
• Anaphylactic shock
• Headache
• Dizziness

Pregnancy:

Pregnancy Category B

Unless a physician determines that the potential benefits outweigh any potential risks, teicoplanin should not be used during confirmed or presumed pregnancy. Studies conducted on animals regarding reproductive effects have not provided evidence of teratogenic effects.

Lactation:

The excretion of teicoplanin in human milk is not currently known. There is also a lack of information regarding the excretion of teicoplanin in animal milk. Therefore, when considering the use of teicoplanin while breastfeeding, a careful decision should be made by weighing the benefits of breastfeeding for the child against the benefits of teicoplanin therapy for the mother. It is important to assess the overall situation and make an informed decision regarding the continuation or discontinuation of either breastfeeding or teicoplanin therapy.

Pediatric:

For children between 2 months and 16 years of age, the following dosage recommendations apply:

● Severe infections and infections in neutropenic patients: The initial three doses should be 10mg/kg administered intravenously every 12 hours. Afterward, a single daily dose of 10mg/kg should be given intravenously.

● Moderate infections: The initial three doses should be 10mg/kg administered intravenously every 12 hours. Following that, a single daily dose of 6mg/kg can be given either intravenously or intramuscularly.

Geriatric Use:

Dosage adjustment is unnecessary unless there is impaired renal function. In such cases, the instructions pertaining to impaired renal function should be adhered to.

Physicians should be knowledgeable as well as vigilant about the treatment and identification of Overdosage of Teicoplanin.

Symptoms:

There have been reported instances of accidental administration of excessive doses of teicoplanin to pediatric patients. For example, in one case, a 29-day-old newborn received an intravenous dose of 400 mg (equivalent to 95 mg/kg), which led to agitation.

Management:

In the event of teicoplanin overdose, treatment should focus on addressing the symptoms and providing symptomatic relief. It is important to note that teicoplanin is not effectively eliminated through hemodialysis and is only slowly removed by peritoneal dialysis.

Pharmacodynamics

Teicoplanin, a glycopeptide antibiotic, exhibits bactericidal activity against both aerobic and anaerobic gram-positive bacteria in laboratory settings. It hinders the growth of susceptible organisms by disrupting cell-wall synthesis at a different site compared to beta-lactam antibiotics. Teicoplanin is effective against various bacteria, including methicillin-resistant staphylococci, streptococci, enterococci, Listeria monocytogenes, micrococci, group J/K corynebacteria, gram-positive anaerobes such as Clostridium difficile, and streptococci.

In vitro studies have demonstrated bactericidal synergy between teicoplanin and aminoglycosides against Staphylococcus aureus. Synergistic effects have also been observed when combining teicoplanin with imipenem against these organisms. Additionally, the combination of teicoplanin and rifampin has shown additive and synergistic effects against Staphylococcus aureus. In vitro, synergy with ciprofloxacin against Staphylococcus epidermidis has also been noted.

Teicoplanin has not shown the ability to develop one-step resistance in vitro, although multi-step resistance has been observed after multiple passages in laboratory settings.

There have been reports of increased minimum inhibitory concentrations (MICs) for teicoplanin in certain strains of Staphylococcus haemolyticus. Teicoplanin does not exhibit cross-resistance with other antibiotic classes, but some cross-resistance has been observed between teicoplanin and the glycopeptide vancomycin among enterococci.

Teicoplanin is absorbed by leukocytes and macrophages, and it maintains its anti-staphylococcal activity within these cells.

Absorption:

● Teicoplanin is administered through parenteral routes, either intravenously or intramuscularly.

● When administered intramuscularly, teicoplanin has a high bioavailability of approximately 90% compared to intravenous administration.

● After six daily intramuscular doses of 200 mg, the maximum teicoplanin concentration (Cmax) reaches an average of 12.1 mg/L at 2 hours after administration.

Distribution:

● Teicoplanin binds strongly to human serum proteins, ranging from 87.6% to 90.8%, with albumin being the primary binding protein.

● Teicoplanin does not distribute in red blood cells.

● The volume of distribution at steady-state (Vss) ranges from 0.7 to 1.4 mL/kg, with higher values observed in studies with longer sampling periods.

● Teicoplanin is distributed primarily in the lung, myocardium, and bone tissues, with tissue/serum ratios greater than 1. It has lower distribution ratios in blister fluids, synovial fluid, peritoneal fluid (0.5 to 1), pleural fluid, and subcutaneous fat tissue (0.2 to 0.5). However, it does not readily penetrate into the cerebrospinal fluid (CSF).

Biotransformation:

● Teicoplanin undergoes minimal metabolism, and the unchanged form is the main compound found in plasma and urine.

● Only 2 to 3% of the administered dose is converted into two metabolites, likely through hydroxylation.

Elimination:

● The primary route of elimination for teicoplanin is through the urinary system, with approximately 80% excreted within 16 days.

● A small portion (2.7%) is excreted in feces via bile excretion within 8 days.

● The elimination half-life of teicoplanin varies between 100 to 170 hours, depending on the duration of blood sampling in studies ranging from 8 to 35 days.