Tetralysal

Tetralysal 300 contains a quantity of lymecycline equivalent to 300mg of tetracycline base as the active ingredient in a mixture of magnesium stearate (lubricant) and levilite (lubricant). Lymecycline is a water-soluble combination of tetracycline, lysine and formaldehyde.

Pharmacology: Pharmacodynamics: Lymecycline is an antibiotic belonging to the tetracycline family (group of the semi-synthetic cyclines).
Antibacterial activity: The natural antibacterial spectrum of lymecycline is that of cyclines: Sensitive species: Brucella, Pasteurella, Chlamydiae, Propionibacterium acnes, Gonococci, Haemophilus, Leptospira, Mycoplasma, Pneumoniae, Ureaplasma urealyticum, Rickettsiae, Treponema pallidum, Vibrio cholerae.
Species with variable sensitivity (10 to 40% resistant strains): Anaerobic organism (Clostridium, Bacteroides, Fusobacterium), Escherichia coli, Klebsiella, Legionella pneumophila, Pneumococci, Proteus morganii, Shigella, staphylococci, streptococci, streptococci groups A, C and G.
Resistant species (MIC ≥ 16 mg/L): Enterobacter, Mycobacterium tuberculosis, Proteus rettgeri, Providencia, Pseudomonas, Serratia, Streptococci groups B and D.
Effects on acne: The exact mechanisms by which tetracyclines reduce lesions of acne vulgaris have not been fully elucidated; however, the effect appears to result in part from the antibacterial activity of the drugs. Following oral administration, the drugs inhibit the growth of susceptible organisms (mainly Propionibacterium acnes) on the surface of the skin and reduce the concentration of free fatty acids in sebum. The reduction in free fatty acids in sebum may be an indirect result of the inhibition of lipase-producing organisms which convert triglycerides into free fatty acids or may be a direct result of interference with lipase production in these organisms. Free fatty acids are comedogenic and are believed to be a possible cause of the inflammatory lesions, e.g. papules, pustules, nodules, cysts, of acne. However, other mechanisms also appear to be involved because clinical improvement of acne vulgaris with oral tetracycline therapy does not necessarily correspond with a reduction in the bacterial flora of the skin or a decrease in the free fatty acid content of sebum.
Pharmacokinetics: Absorption: Absorption is rapid. Effective plasma levels are reached within the first hour following drug intake. The peak plasma level is reached within 3 to 4 hours after oral administration. Concurrent food intake, milk in particular, does not significantly modify the absorption of lymecycline.
Distribution: Oral administration of 300 mg, in the adult, gives rise to: a peak plasma level of 1.6 to 4 μg/mL; a highly variable residual concentration (0.29 to 2.19 μg/mL); a plasma half-life of approximately 10 hours.
Repeated administration results in a steady mean plasma concentration between 2.3 and 5.8 μg/ml. Wide intra and extra-cellular diffusion, under normal dosage conditions, results in effective concentrations in most body tissues and fluids, and notably in the lungs, bones, muscles, liver, bladder, prostate, bile and urine.
Excretion/elimination: The product is principally excreted in urine and secondarily in the bile. About 65% of the administered dose is eliminated within 48 hours.

The therapeutic indications of Tetralysal 300 are derived from the antibacterial and pharmacokinetic properties of lymecycline. They take into account the place of this antibiotic within all antimicrobial agents available as well as the current knowledge of lymecycline-resistant organisms. The product should be reserved for the treatment of Brucella infection, Pasteurellae infection, pulmonary, genito-urinary and ophthalmologic infections due to Chlamydiae, pulmonary and genito-urinary infections due to Mycoplasma, Rickettsiae infection, Coxiella burnetti (Q fever), Gonococci infection, respiratory, broncho-pulmonary infections due to Haemophilus influenzae, particularly when there is an acute exacerbation of chronic bronchitis, Treponema (tetracyclines are indicated in syphilis only when the patient is allergic to β-lactamines), Spirochetes (lyme disease, leptospirosis), cholera, acne (cutaneous manifestations in relation with Propionibacterium acnes).

Adults: The usual dosage for the chronic treatment of acne is 1 capsule daily (300 mg/day). Treatment should be continued for at least 8 weeks. For other infections, the usual dosage is 1 capsule b.d. (600 mg/day). If higher doses are required, 3-4 capsules (900-1200 mg) may be given over 24 hours. Lower doses may be given for prophylaxis. In the management of sexually transmitted disease both partners should be treated.
Elderly: As for other tetracyclines, no specific dose adjustment is required.
Paediatric population: The safety and efficacy of Tetralysal in children aged under 12 years of age have not been established. No data are available. For children over the age of 12 years, the adult dosage may be given. For children under the age of 8 years, see Contraindications.
Methods of administration: It should be taken with an adequate amount of fluid in order to reduce the risk of esophageal irritation and ulceration.

Acute overdosage is rare with antibiotics and there is no specific treatment. Should this happen gastric emptying should be considered. Supportive measures should be instituted as required and a high fluid intake maintained.

Patients hypersensitive to the active substance or, to other tetracycline or to any of the excipients.
The use of this product to be avoided in children under 8 years of age due to the risk of permanent dental staining and enamel hypoplasia.
Concurrent treatment with retinoids (see Interactions).

Solid dosage forms of the tetracyclines may cause oesophageal irritation and ulceration. To avoid oesophageal irritation and ulceration, adequate fluids (water) should be taken with this medicinal product.
Caution should be exercised if the product is administered to patients with impaired renal or hepatic functions.
Overdosage could result in hepatotoxicity.
Due to the risks of photosensitivity, it is recommended to avoid exposure to direct sunlight and ultraviolet light during the treatment which should be discontinued if erythematous cutaneous manifestations occur.
The use of expired tetracyclines can lead to renal tubular acidosis (Pseudo-Fanconi syndrome) readily reversible when treatment is discontinued altogether.
Effects on the ability to drive and use machines: Not applicable.

Tetracyclines readily cross the placental barrier and are distributed into milk. Therefore, Tetralysal should not be administered to pregnant or breast-feeding women. Tetracyclines are selectively absorbed by developing bones and teeth and may cause dental staining and enamel hypoplasia in embryos and children.

See table.

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Some adverse effects are reported with tetracycline therapy in general: Dental dyschromia and/or enamel hypoplasia may occur if the product is administered in children younger than 8 years of age.
Haemolytic anaemia, eosinophilia and other hematologic disorders have been reported with tetracycline therapy.
Extra-renal hyperazotemia linked to an anti-anabolic effect which may be intensified by the association with diuretics has been reported with tetracycline therapy.
Treatment should cease if any evidence of raised intracranial pressure develop during treatment with Tetralysal.

Oral Retinoids and Vitamin A (above 10,000 IU/day): risk of intracranial hypertension.
Simultaneous administration of iron preparations and anti-acids, magnesium/aluminium and calcium hydroxides, oxides, salts, cholestyramine, bismuth chelates, sucralfate and quinapril may decrease cycline absorption. Medicinal products which increase gastric pH may reduce the absorption of tetracyclines. Enzyme inducers such as barbiturates, carbamazepine, phenytoin may accelerate the decomposition of tetracycline due to enzyme induction in the liver thereby decreasing its half-life. Consequently, a minimum 2-hour gap is necessary between the two treatments.
The effect of oral coumarin-type anticoagulants could be increased with an increased risk of haemorrhage.
Bacteriostatic medicinal products including lymecycline may interfere with the bactericidal action of penicillin and beta-lactam antibiotics. It is advisable that tetracycline-class drugs and penicillin should not therefore be used in combination.
Tetracylcines and methoxyflurane used in combination have been reported to result in fatal renal toxicity.
Some adverse effects have been reported with tetracycline therapy when used in combination with lithium; an interaction between lithium and the tetracycline class is a recognized interaction. Specifically, a combination of lymecycline with lithium may cause an increase in serum lithium levels.
Laboratory test interferences: Lymecycline could cause false positive urine glucose determinations. It could also interfere with fluorometric determinations of urine catecholamines resulting in falsely increased values (Hingerty's method).

Tetralysal 300 should be stored in a cool dry place.

Tetracyclines / Acne Treatment Preparations

J01AA04 - lymecycline ; Belongs to the class of tetracyclines. Used in the systemic treatment of infections.

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