Teicoplanin

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 at least 10 mg/L when measured by HPLC, or at least 15 mg/L when measured by FPIA method.

After the fourth day of treatment:

• In mild and moderate renal insufficiency (creatinine clearance 30-80 mL/min): maintenance dose should be halved, either by administering the dose every two days or by administering half of this dose once a day.
• In severe renal insufficiency (creatinine clearance less than 30 mL/min) and in haemodialysed patients: dose should be one-third the usual dose, either by administering the initial unit dose every third day or by administering one-third of this dose once a day.

Teicoplanin is not removed by haemodialysis.

Teicoplanin and aminoglycoside solutions are incompatible and must not be mixed for injection; however, they are compatible in dialysis fluid and may be freely used in the treatment of CAPD-related peritonitis.

Teicoplanin should be used with care in conjunction with or sequentially with other medicinal products with known nephrotoxic or ototoxic potential. These include aminoglycosides, colistin, amphotericin B, ciclosporin, cisplatin, furosemide, and ethacrynic acid. However, there is no evidence of synergistic toxicity in combinations with teicoplanin.

Thrombocytopenia has been reported with teicoplanin. Periodic haematological examinations are recommended during treatment, including complete cell blood count.

After a single intravenous loading dose of 6 mg/kg bodyweight, 20 mg/L is administered in the bag of the dialysis solution in the first week, 20 mg/L in different bags the second week and then 20 mg/L in the overnight bag in the third week.

As with other glycopeptides, ototoxicity (deafness and tinnitus) has been reported in patients treated with teicoplanin. Patients who develop signs and symptoms of impaired hearing or disorders of the inner ear during treatment with teicoplanin should be carefully evaluated and monitored, especially in case of prolonged treatment and in patients with renal insufficiency. Patients receiving teicoplanin in conjunction with or sequentially with other medicinal products with known neurotoxic/ototoxic potential (aminoglycosides, ciclosporin, cisplatin, furosemide and ethacrynic acid) should be carefully monitored and the benefit of teicoplanin evaluated if hearing deteriorates.

Special precautions must be taken when administering teicoplanin in patients who require concomitant treatment with ototoxic and/or nephrotoxic medicinal products for which it is recommended that regular haematology, liver and kidney function tests are carried out.

Teicoplanin must be administered with caution in patients with known hypersensitivity to vancomycin, as crossed hypersensitivity reactions, including fatal anaphylactic shock, may occur.

However, a prior history of “red man syndrome” with vancomycin is not a contraindication to the use of teicoplanin.

Teicoplanin is not removed by haemodialysis.

Life-threatening or even fatal cutaneous reactions Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) have been reported with the use of teicoplanin. If symptoms or signs of SJS or TEN (e.g. progressive skin rash often with blisters or mucosal lesions) are present teicoplanin treatment should be discontinued immediately.

Serious, life-threatening hypersensitivity reactions, sometimes fatal, have been reported with teicoplanin (e.g. anaphylactic shock). If an allergic reaction to teicoplanin occurs, treatment should be discontinued immediately and appropriate emergency measures should be initiated.

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.

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 breast-feeding or to continue/discontinue therapy with teicoplanin should be made taking into account the benefit of breast-feeding to the child and the benefit of teicoplanin therapy to the mother.

Fertility

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

Teicoplanin has minor influence on the ability to drive and use machines. Teicoplanin can cause dizziness and headache. The ability to drive or use machines may be affected. Patients experiencing these undesirable effects should not drive or use machines.

List of adverse reactions

In the list below all the adverse reactions, which occurred at an incidence greater than placebo and more than one patient are listed using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Adverse reactions should be monitored when teicoplanin doses of 12 mg/kg body weight twice a day are administered.

Infections and infestations

Rare: Abscess

Not known: Superinfection (overgrowth of non-susceptible organisms)

Blood and the lymphatic system disorders

Uncommon: Leucopenia, thrombocytopenia, eosinophilia

Not known: Agranulocytosis, neutropenia

Immune system disorders

Uncommon: Anaphylactic reaction (anaphylaxis)

Not known: Drug reaction with eosinophilia and systemic symptoms (DRESS), anaphylactic shock

Nervous system disorders

Uncommon: Dizziness, headache

Not known: Seizures

Ear and Labyrinth disorders

Not known: Deafness, hearing loss, tinnitus, vestibular disorder

Vascular disorders

Uncommon: Phlebitis

Not known: Thrombophlebitis

Respiratory, thoracic and mediastinal disorders

Uncommon: Bronchospasm

Gastro-intestinal disorders

Uncommon: Diarrhoea, vomiting, nausea

Skin and subcutaneous tissue disorders

Common: Rash, erythema, pruritus

Rare: Red man syndrome (e.g. Flushing of the upper part of the body).

Not known: Toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, angioedema, dermatitis exfoliative, urticaria

Renal and Urinary disorders

Uncommon: Blood creatinine increased

Not known: Renal failure (including renal failure acute)

General disorders and administration site conditions

Common: Pain, pyrexia

Not known: Injection site abscess, chills (rigors)

Investigations

Uncommon: Transaminases increased (transient abnormality of transaminases), blood alkaline phosphatase increased (transient abnormality of alkaline phosphatase), blood creatinine increased (transient rise of serum creatinine)