Teicoplanin

These indications are based on manufacturer information for both originator and generic products. For product specific registered indications, please refer to product specific manufacturer information

Registered South African indications:

• Serious gram-positive infections, including those which cannot be treated with other antimicrobial agents
• Blood infections
  - Septicaemia due to Staphylococcus aureus, Listeria monocytogenes, Clostridium difficile, coagulase-negative staphylococci (sensitive or resistant to methicillin), streptococci and enterococci
• Respiratory infections
  - Caused by methicillin-resistant Staphylococcus aureus, streptococci and Gram-positive anaerobes including peptococci
• Cardiac infections
  - Endocarditis due to Staphylococcus aureus, Corynebacterium jeikeium, Listeria monocytogenes, coagulase negative staphylococci (sensitive or resistant to methicillin), streptococci and enterococci
• Skin and soft tissue infections
  - Caused by Staphylococcus aureus, coagulase-negative staphylococci (sensitive or resistant to methicillin), streptococci, micrococci and Gram-positive anaerobes including peptococci
• Urinary tract infections
  - Caused by enterococci
• Bone infections
  - Osteomyelitis due to Staphylococcus aureus, coagulase-negative staphylococci (sensitive or resistant to methicillin), streptococci, enterococci and Gram-positive anaerobes
• Peritonitis associated with chronic ambulatory peritoneal dialysis (CAPD)
  - Due to Staphylococcus aureus and enterococci
• Prophylaxis in high risk patients unable to receive penicillin in orthopaedic and vascular surgery at risk of Gram-positive infection
• Antibiotic-associated diarrhoea, including pseudomembranous colitis, caused by Clostridium difficile

Contraindications

South African recommendations

• Hypersensitivity to the active ingredient or any of its excipients
• Safety and efficacy have not been established in children less than 3 years of age
• Pregnancy
• Lactation
• Teicoplanin must not be injected into the subarachnoid space

Recommendations in other jurisdictions

• Hypersensitivity to teicoplanin or to any of the excipients

Cautions

• Known hypersensitivity to vancomycin
• Pregnancy (Recommendations in other jurisdictions) 
• Breastfeeding (Recommendations in other jurisdictions)
• Renal impairment
• Hepatic impairment
• High loading doses (12mg/kg, 12hrly)
• Prolonged use
• Coadministration with ototoxic/neurotoxic/nephrotoxic agents
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inj

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Infections caused by: Gram-positive bacteria such as Staphylococcus aureus, Listeria monocytogenes, Clostridium difficile, coagulase-negative staphylococci (sensitive or resistant to methicillin), Streptococci, Enterococci, Gram-positive anaerobes including peptococci; Corynebacterium jeikeium, Micrococci

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

Serious gram-positive infections, including those which cannot be treated with other antimicrobial agents
Blood infections
- Septicaemia due to Staphylococcus aureus, Listeria monocytogenes, Clostridium difficile, coagulase-negative staphylococci (sensitive or resistant to methicillin), streptococci and enterococci
Respiratory infections
- Caused by methicillin-resistant Staphylococcus aureus, streptococci and Gram-positive anaerobes including peptococci
Cardiac infections
- Endocarditis due to Staphylococcus aureus, Corynebacterium jeikeium, Listeria monocytogenes, coagulase negative staphylococci (sensitive or resistant to methicillin), streptococci and enterococci
Skin and soft tissue infections
- Caused by Staphylococcus aureus, coagulase-negative staphylococci (sensitive or resistant to methicillin), streptococci, micrococci and Gram-positive anaerobes including peptococci
Urinary tract infections
- Caused by enterococci
Bone infections
- Osteomyelitis due to Staphylococcus aureus, coagulase-negative staphylococci (sensitive or resistant to methicillin), streptococci, enterococci and Gram-positive anaerobes

Moderate infections (Skin and soft tissue infections, urinary tract infections, lower respiratory tract infections)

• IV: Loading dose: First day: 400mg, as a single dose; Maintenance: IV/IM: 200mg, daily

Severe infections (Joint and bone infections, septicaemia, endocarditis)

• IV: Loading dose: 400mg, every 12hrs for the first 3 doses; Maintenance: IV/IM: 400mg, daily; In some clinical situations, such as infected, severely burned patients or Staphylococcus aureus endocarditis: Maintenance: Up to 12mg/kg may be required; Treatment duration: Endocarditis and osteomyelitis: 3 weeks or longer

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Standard doses of 200mg and 400mg are equivalent to mean doses of 3mg/kg and 6mg/kg respectively

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Monitoring the plasma concentrations: If checks are carried out on the teicoplanin serum level in patients with severe infections, then the minimum serum level should not be below 10mg/l (measured just before the following dose)

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Prophylaxis in high risk patients unable to receive penicillin in orthopaedic and vascular surgery at risk of Gram-positive infection

• IV: 400mg, as a single dose at induction of anaesthesia

Antibiotic-associated diarrhoea, including pseudomembranous colitis, caused by Clostridium difficile

• IV (oral): 200mg, twice a day; After reconstitution, the contents of the vial may be admin. as an oral solution; Treatment duration: 10 days

Peritonitis associated with chronic ambulatory peritoneal dialysis (CAPD)
- Due to Staphylococcus aureus and enterococci

• IV: Loading dose: 400mg, as a single dose; If febrile: First week: 20mg/l, per bag; Second week: 20mg/l, per alternate bags; Third week: 20mg/l, in the overnight dwell bag

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Do not keep mixed solutions for longer than 24 hours

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The majority of patients, with infections caused by organisms sensitive to teicoplanin, show a therapeutic response within 2-3 days. The duration of therapy is determined by the type and severity of the infection, and the clinical response of the patient. Treatment should be continued for at least three days after the disappearance of clinical symptoms and after the patient has become afebrile. In cases of endocarditis or osteomyelitis at least three weeks of teicoplanin treatment is recommended. Teicoplanin should not be administered for longer than four months

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Determination of teicoplanin serum concentrations may optimise therapy. In severe infections, trough serum concentrations should not be less than 10mg/l. Peak concentrations measured 1 hour after a 400mg IV dose are usually in the range of 20-50mg/l; peak serum concentrations of up to 250mg/l have been reported after IV doses of 25mg/kg. No relationship has yet been established between plasma concentration and toxicity

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The reconstituted teicoplanin injection is given intravenously as a bolus or by 30 minute infusion or by intramuscular injection. A once daily dosage regime is usually followed but, in cases of severe infection, a second injection should be administered on the first day in order to reach the required serum concentrations more rapidly

Paed. forms avail. in SA and covered in this monograph: inj

Paed. dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Infections caused by: Gram-positive bacteria such as Staphylococcus aureus, Listeria monocytogenes, Clostridium difficile, coagulase-negative staphylococci (sensitive or resistant to methicillin), Streptococci, Enterococci, Gram-positive anaerobes including peptococci; Corynebacterium jeikeium, Micrococci

Specific doses based on individual indications

Please note that the dosages below should be used in combination with regional guidelines, taking into account local antibiotic sensitivities

Serious gram-positive infections, including those which cannot be treated with other antimicrobial agents
Blood infections
- Septicaemia due to Staphylococcus aureus, Listeria monocytogenes, Clostridium difficile, coagulase-negative staphylococci (sensitive or resistant to methicillin), streptococci and enterococci
Respiratory infections
- Caused by methicillin-resistant Staphylococcus aureus, streptococci and Gram-positive anaerobes including peptococci
Cardiac infections
- Endocarditis due to Staphylococcus aureus, Corynebacterium jeikeium, Listeria monocytogenes, coagulase negative staphylococci (sensitive or resistant to methicillin), streptococci and enterococci
Skin and soft tissue infections
- Caused by Staphylococcus aureus, coagulase-negative staphylococci (sensitive or resistant to methicillin), streptococci, micrococci and Gram-positive anaerobes including peptococci
Urinary tract infections
- Caused by enterococci
Bone infections
- Osteomyelitis due to Staphylococcus aureus, coagulase-negative staphylococci (sensitive or resistant to methicillin), streptococci, enterococci and Gram-positive anaerobes

Moderate infections

Younger than 3 years

• Contraindicated

Older than 3 years

• IV: Loading dose: 10mg/kg, 12hrly for first 3 doses; Maintenance: IV/IM: 6mg/kg, dly

Severe infections and neutropenic patients

Below 3 years

• Contraindicated

Older than 3 years

• IV: Loading dose: 10mg/kg, 12hrly for first 3 doses; Maintenance: 10mg/kg, dly

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The majority of patients, with infections caused by organisms sensitive to teicoplanin, show a therapeutic response within 2-3 days. The duration of therapy is determined by the type and severity of the infection, and the clinical response of the patient. Treatment should be continued for at least three days after the disappearance of clinical symptoms and after the patient has become afebrile. In cases of endocarditis or osteomyelitis at least three weeks of teicoplanin treatment is recommended. Teicoplanin should not be administered for longer than four months 14

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The reconstituted teicoplanin injection is given intravenously as a bolus or by 30 minute infusion or by IM injection. A once daily dosage regime is usually followed but, in cases of severe infection, a second injection should be administered on the first day in order to reach the required serum concentrations more rapidly

Pregnancy

South African recommendations

• Contraindicated
• The safety of teicoplanin has not been established and it should not be used during pregnancy

Recommendations in other jurisdictions

• Caution; positive evidence of risk in animal studies 
• There are a limited amount of data from the use of teicoplanin in pregnant women
• Studies in animals have shown reproductive toxicity at high doses: in rats, there was an increased incidence of stillbirths and neonatal mortality. The potential risk for humans is unknown
• Therefore, teicoplanin should not be used during pregnancy unless clearly necessary. A potential risk of inner ear and renal damage to the foetus cannot be excluded

Breastfeeding

South African recommendations

• Contraindicated
• It is not known whether teicoplanin passes into breast milk
• The safety of teicoplanin has not been established and it should not be used during lactation

Recommendations in other jurisdictions

• Caution; not recommended
• It is unknown whether teicoplanin is excreted in human milk. There is no information on the excretion of teicoplanin in animal milk  
• A decision on whether to continue/discontinue breastfeeding or to continue/discontinue therapy with teicoplanin should be made taking into account the benefit of breastfeeding to the child and the benefit of teicoplanin therapy to the mother

Fertility

• Animal reproduction studies have not shown evidence of impairment of fertility

Renal Impairment

South African recommendations

• Caution; dose adjustment recommended 

CrCl (ml/min)	Initial: Day 1-3	From the 4th day of treatment
40-60	No adjustment necessary	Reduce dose by half, either by administering dose, 48hrly OR administering half the dose, 24hrly
<40 and in haemodialysed patients	No adjustment necessary	Administer one-third of the normal dose, either by administering the initial unit dose, 72hrly OR administering one-third the unit dose, 24hrly

Unless measurement of the serum concentrations can be guaranteed to accompany the therapy, patients with a creatinine clearance lower than or equal to 20ml/min must be excluded from therapy with teicoplanin. Teicoplanin is not removed by dialysis

Recommendations in other jurisdictions

• Caution; dose adjustment recommended

CrCl (ml/min)	Initial: Day 1-3	From the 4th day of treatment
30-80	No adjustment necessary	Reduce maintenance dose by half, either by administering dose, 48hrly OR administering half the dose, 24hrly
<30 and in haemodialysed patients	No adjustment necessary	Administer one-third of the usual dose, either by administering the initial unit dose, 72hrly OR administering one-third the usual dose, 24hrly

Dose adjustment is not required until the fourth day of treatment, at which time dosing should be adjusted to maintain a serum trough concentration of ≥10mg/l when measured by HPLC, or ≥15mg/l when measured by fluorescence polarisation immunoassay (FPIA) method
Continuous ambulatory peritoneal dialysis (CAPD): After a single IV loading dose of 6mg/kg, administer 20mg/l in the bag of the dialysis solution in the first week; Repeat in different bags during the second week; then administer 20mg/l in the overnight bag during the third week

Hepatic Impairment

• Caution; no information available

Elderly

• No dose adjustment recommended

Obesity

• Caution; dose adjustment recommended
  In overweight patients it is recommended that the dose be adapted to the weight of the patient as follows: Moderate infections 3mg/kg; Severe infections 6mg/kg

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dizziness
• Headache
• Seizures

Cardiovascular Disorders

• Phlebitis
• Thrombophlebitis

Respiratory Disorders

• Bronchospasm

Gastrointestinal Disorders

• Diarrhoea
• Nausea and vomiting

Hepatobiliary Disorders

• Increased transaminases
• Increased blood alkaline phosphatase

Genitourinary Disorders

• Increased blood creatinine
• Renal failure
  - Acute renal failure

Skin and Subcutaneous Tissue Disorders

• Rash
• Erythema
• Pruritus
• Red man syndrome
  - Flushing of the upper part of the body)
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome
• Erythema multiforme
• Angioedema
• Exfoliative dermatitis
• Urticaria

Immune, Blood and Lymphatic System Disorders

• Abscess
• Superinfection (overgrowth of non-susceptible organisms)
• Leucopenia
• Thrombocytopenia
• Eosinophilia
• Agranulocytosis
• Neutropenia
• Anaphylactic reaction
  - Anaphylaxis
• Drug reaction with eosinophilia and systemic symptoms
• Anaphylactic shock
• Fever
• Chills

Sensory Disorders

• Deafness
• Hearing loss  
• Tinnitus
• Vestibular disorder

Other

• Pain
• Injection site abscess

• Nephrotoxic agents
• Ototoxic agents
• Neurotoxic agents
• Aminoglycosides
• Colistin
• Amphotericin B
• Ciclosporin
• Cisplatin
• Furosemide
• Ethacrynic acid

Other interactions

• Aminoglycoside solutions (when mixed for injections; however teicoplanin and aminoglycoside solutions are compatible in dialysis fluid)

• Serum trough concentrations
  - Trough serum concentrations should be monitored at steady state after completion of loading dose regimen
  - During maintenance treatment, trough serum concentrations can be performed weekly
• Renal function

Specific cases may require

• Audiometry

Additional observations

• Adverse reactions should be monitored when teicoplanin doses of 12mg/kg, 12hrly are administered

Administration directions

• The entire contents (3.2ml water for injection) of the solvent in the accompanying ampoule is used to reconstitute the lyophilised teicoplanin to produce the ready-to-use solution by slowly injecting the solvent into the vial with the dry substance
• The vial is then rolled, not shaken, until the lyophilised powder is completely dissolved
• Care must be taken to avoid the formation of foam. The solution must be left to stand for approximately 15min if foam develops during the preparation of the injection solution, to allow for the foam to disappear
• For intravenous injection, teicoplanin is injected either directly intravenously; or into the proximal end of a drip line after clamping the line
• Teicoplanin can be injected as a bolus within one minute
• Teicoplanin can be administered by infusion, it is dissolved in 20-50ml of infusion solution and administered over 20-30min by the infusion route
• Teicoplanin can also be injected intramuscularly

Teicoplanin can be administered in the following infusion solutions:

• 0.9% sodium chloride solution (saline)
• Ringer's lactate solution
• Hartman solution
• 5% glucose solution
• 0.18% sodium chloride and 4% dextrose solution
• Reconstituted solutions of teicoplanin should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would not be longer than 24 hours at 2-8°C, unless reconstitution/dilution has taken place under controlled and validated aseptic conditions

Incompatibilities

• Solutions of teicoplanin and aminoglycosides are incompatible and should not be mixed before injection

Teicoplanin inhibits the growth of susceptible organisms by interfering with cell-wall biosynthesis at a site different from that affected by beta-lactams. Peptidoglycan synthesis is blocked by specific binding to D-alanyl-D-alanine residues.

Spectrum of activity: Aerobic gram positive bacteria such as Corynebacterium jeikeium; Enterococcus faecalis; Staphylococcus aureus (including methicillin-resistant strains); Streptococcus agalactiae; Streptococcus dysgalactiae subsp. equisimilis; (Group C & G streptococci); Streptococcuspneumoniae; Streptococcus pyogenes; Streptococci in the viridans group; Anaerobic gram positive bacteria such as Clostridium difficile; Peptostreptococcus spp.; Staphylococcus epidermis; Staphylococcus sp., coagulase negative

Injection (per vial) 200mg

• Aspen teicoplanin 200 (Pharmacare)
• Dyna teicoplanin (Pharma Dynamics)
• Litha Teicoplanin 200 (Litha Pharma)
• Planitec 200 (Sandoz)
• Spec teicoplanin 200 (Specpharm) 
• Tarbact (Ranbaxy)
• Targocid 200 (Sanofi) originator
• Tegorid IV 200 (Ranbaxy)
• Teicowin 200 (Zentiva)

Injection (per vial) 400mg

• Aspen teicoplanin 400 (Pharmacare)
• Cipla teicoplanin (Cipla)
• Dyna teicoplanin (Pharma Dynamics)
• Litha Teicoplanin 400 (Litha Pharma)
• Spec teicoplanin 400 (Specpharm) 
• Targocid 400 (Sanofi) originator
• Tarbact (Ranbaxy)
• Tegorid IV 400 (Ranbaxy)
• Teicowin 400 (Zentiva)