Tetralysal
Yellow and red hard gelatin capsules containing lymecycline equivalent to 300mg tetracycline base.
ATC code: J01AA04 Tetracyclines provide bacteriostatic action at the available plasma and tissue concentrations and are effective against intracellular and extracellular organisms. Their mechanism of action is based on an inhibition of ribosomal protein synthesis. Tetracyclines block the access of the bacterial aminoacyl-tRNA to the mRNA- ribosome complex by binding to the 30S subunit of the ribosome, thus preventing the addition of amino acids to the growing peptide chain in protein synthesis. When given at therapeutically attainable concentrations their toxic effect is limited to the bacterial cells. 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.
Tetracycline resistance in propionibacteria is usually associated with a single point mutation within the gene encoding 16S rRNA. Clinical isolates resistant to tetracycline were found to have cytosine instead of guanine at a position cognate with Escherichia coli base 1058. There is no evidence that ribosome mutations can be transferred between different strains or species of propionibacteria, or between propionibacteria and other skin commensals. Resistance to the tetracyclines is associated with mobile resistance determinants in both staphylococci and coryneform bacteria. These determinants are potentially transmissible between different species and even different genera of bacteria. In all three genera, cross-resistance with the macrolide-lincosamide-streptogramin group of antibiotics cannot be ruled out. Strains of propionibacteria resistant to the hydrophilic tetracyclines are cross- resistant to doxycycline and may or may not show reduced susceptibility to minocycline.
For tetracycline resistance in anaerobic and most aerobic bacteria, the breakpoints as set by the NCCLS are: Susceptible MIC < 4 mg/L Intermediate MIC 8 mg/L Resistant MIC > 16 mg/L In cutaneous propionibacteria, mutational resistance is associated with MICs of tetracycline > 2mg/L. Susceptibility table The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable. Susceptibility to tetracyclines of species relevant to the approved indication
| Commonly susceptible species |
| Gram-positive aerobes |
| None of relevance |
| Gram-negative aerobes |
| None of relevance |
| Anaerobes |
| Propionbacterium acnes (clinical isolates) * |
| Other |
| None of relevance |
| Species for which acquired resistance may be a problem (defined as >10% resistant within any European country) |
| Gram-positive aerobes |
| S. aureus (methicillin susceptible) |
| S. aureus (methicillin resistant) + |
| Coagulase-negative staphylococci (methicillin susceptible) |
| Coagulase-negative staphylococci (methicillin resistant) + |
| Corynebacterium spp |
| Species for which acquired resistance may be a problem (defined as >10% resistant within any European country) |
| Gram-negative aerobes |
| None of relevance |
| Anaerobes |
| Propionibacterium acnes (isolates from acne) * + |
| Other (microaerophile) |
| None of relevance |
| Inherently resistant species |
| None of relevance |
However, even if resistance to cutaneous propionibacteria is detected, this does not automatically translate into therapeutic failure, since the anti-inflammatory activity of the tetracyclines is not compromised by resistance in the target bacteria.
Lymecycline is more readily absorbed from the gastro-intestinal tract than tetracycline, with a peak serum concentration of approximately 2mg/L after 3 hours following a 300 mg dose. In addition, similar blood concentrations are achieved with small doses. When the dose is doubled an almost correspondingly higher blood concentration has been reported to occur. The serum half-life of lymecycline is approximately 10 hours.
Tetralysal is a broad spectrum antibiotic and is recommended for the treatment of all infections caused by tetracycline sensitive organisms and may be utilised in all conditions where tetracycline therapy is indicated. In common with other tetracyclines it is indicated in penicillin-sensitive patients for the treatment of staphylococcal infections. Typical infections include: Ear, nose and throat infections; Acute and chronic bronchitis (including prophylaxis); Infections of the gastrointestinal and urinary tracts; Non-gonococcal urethritis of chlamydial origin; and other chlamydial infections such as trachoma; acne; rickettsial fevers; soft tissue infections.
One capsule morning or night with or without milk or food. If higher doses are required 3-4 capsules of 300 mg may be given over 24 hours. Lower doses may be given for prophylaxis and for the treatment of recalcitrant acne; in such cases treatment should be continued for at least eight weeks. In the management of sexually transmitted diseases both partners should be treated.
Tetralysal should not be administered to children under the age of 8 years.
Hypersensitivity to lymecycline or any other tetracycline or to any of the excipients. Tetracyclines are selectively absorbed by developing bones and teeth and may cause dental staining and enamel hypoplasia. In addition these compounds readily cross the placental barrier and therefore Tetralysal should not be administered to pregnant women or children below the age of 8 years. As Tetralysal is mainly excreted by the kidneys it should not be administered to patients with overt renal insufficiency.
Prolonged use of broad spectrum antibiotics may result in the appearance of resistant organisms and superinfection. Care should be exercised in administering tetracyclines to patients with hepatic impairment. Tetracyclines may cause photosensitivity reactions; however, very rare cases have been reported with lymecycline. May cause exacerbation of systemic lupus erythematosus. Can cause weak neuromuscular blockade so should be used with caution in Myasthenia Gravis.
Tetracyclines are selectively absorbed by developing bones and teeth and may cause dental staining and enamel hypoplasia. In addition these compounds readily cross the placental barrier and therefore Tetralysal 300 should not be given to pregnant or lactating women.
No studies on the effects on the ability to drive and use machines have been performed
The most frequently reported adverse events with Tetralysal are gastrointestinal disorders of nausea, abdominal pain, diarrhoea and nervous system disorder of headache. The most serious adverse events reported with Tetralysal are Stevens Johnson syndrome, anaphylactic reaction, angioneurotic oedema and intracranial hypertension.
| System Organ Class | Frequency | Adverse Reaction |
| Blood and lymphatic system disorders | Unknown | Neutropenia Thrombocytopenia |
| Eye disorders | Unknown | Visual disturbance |
| Gastrointestinal disorders | Common | Nausea |
| ( 1/100 and <1/10) | Abdominal pain Diarrhoea | |
| Unknown | Epigastralgia Glossitis Vomiting Enterocolitis | |
| General disorders and administration site conditions | Unknown | Pyrexia |
| Hepatobiliary disorders | Unknown | Jaundice |
| Immune system disorder | Unknown | Anaphylactic reaction Hypersensitivity Urticaria Angioneurotic oedema |
| Investigations | Unknown | Transaminases increased Blood alkaline phosphatase increased Blood bilirubin increased |
| Nervous system disorders | Common ( 1/100 and <1/10) | Headache |
| Unknown | Dizziness Intracranial hypertension | |
| Skin and subcutaneus tissues disorders | Unknown | Erythematous rash Photosensitivity Pruritus Stevens Johnson syndrome |
General tetracyclines adverse events:
Benign intracranial hypertension and bulging fontanelles in infants were reported with tetracyclines with possible symptoms of headaches, visual disturbances including blurring of vision, scotomata, diplopia or permanent visual loss. The following adverse effects were reported with tetracyclines in general and may occur with Tetralysal: dysphagia, oesophagitis, oesophageal ulceration, pancreatitis, teeth discolouration, hepatitis, hepatic failure. Dental dyschromia and/or enamel hypoplasia may occur if the product is administered in children younger than 8 years of age As with all antibiotics overgrowth of non-susceptible organisms may cause candidiasis, pseudomembranous colitis (Clostridium Difficile overgrowth), glossitis, stomatitis, vaginitis or staphyloccocal enterocolitis.
The absorption of tetracyclines may be affected by the simultaneous administration of calcium, aluminium, magnesium, bismuth and zinc salts, antacids, Bismuth containing ulcer-healing medicines, iron preparations and quinapril. Unlike earlier tetracyclines, absorption of Tetralysal 300 is not significantly impaired by moderate amounts of milk. Concomitant use of oral retinoids should be avoided as this may increase the risk of benign intracranial hypertension. An increase in the effects of anticoagulants may occur with tetracyclines. Concomitant use of diuretics should be avoided. Although not reported for Tetralysal 300, a few cases of pregnancy or breakthrough bleeding have been attributed to the concurrent use of tetracycline or oxytetracycline with oral contraceptives.
There is no specific treatment but gastric lavage should be performed as soon as possible. Supportive measures should be instituted as required and a high fluid intake maintained.
Tetralysal 300mg should be stored at or below 25degC protected from light.
Prescription Medicine.
Capsule, 300mg, 28's.
Magnesium stearate Colloidal hydrated silica The capsule shells contain: gelatin titanium dioxide (E171) erythrosine (E127) quinoline yellow (E104) indigotine (E132)
No specific information is presented given the vast experience gained with the use of tetracyclines in humans over the last forty years.
Galderma Australia Pty Ltd 9 Rodborough Road,
Frenchs Forest, NSW 2086 Distributed in New Zealand by: Healthcare Logistics 58 Richard Pearse Drive Airport Oaks Auckland Ph (09) 918 5100 Fax (09) 918 5101
9 April 2010