Lymecycline 408 Mg Capsule Hard
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Lymecycline 408 mg capsule, hard
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 408mg of lymecycline equivalent to 300mg tetracycline For the full list of excipients, see section 6.1
3 PHARMACEUTICAL FORM
Capsule, hard
Hard gelatin capsule size 0, blue cap and white body
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Lymecycline is indicated for the treatment of moderate to severe acne vulgaris (see
sections 4.4 and 5.1).
Consideration should be given to official guidance on the appropriate use of antibacterial agents
4.2 Posology and method of administration
Posology
Adults:
The usual dosage for the long-term treatment of moderate to severe acne is 1 capsule daily. Treatment should be continued for at least 8 weeks to 12 weeks, however it is important to limit the use of antibiotics to the shortest possible period and discontinue their use when further improvement is unlikely. The treatment should not exceed a duration of 6 months.
Elderly:
As for other tetracyclines, no specific dose adjustment is required.
Paediatric population
Lymecycline is contraindicated in children under the age of 12 years. For children over the age of 12 years the adult dosage may be given.
Renal impairment:
The excretion rate for tetracycline is reduced in case of renal insufficiency and thus normal dosage may lead to accumulation. In case of renal insufficiency it is recommended to lower the dose and possibly to control serum levels.
Method of administration
The capsules must be taken with at least half a glass of water whilst in an upright position. It should be taken with a light meal without dairy products
4.3 Contraindications
Lymecycline is contraindicated in:
- hypersensitivity to the active substance, any other tetracycline or to any of the excipients listed in section 6.1.
- patients with severe renal impairment
- children less than 12 years.
- pregnancy and during breast feeding.
- concurrent treatment with oral retinoids and use in association with systemic retinoids (see sections 4.5 and 4.8).
4.4 Special warnings and precautions for use
Prolonged use of broad spectrum antibiotics may result in the appearance of resistant organisms and superinfections.
Cross-resistance between tetracyclines may develop in micro-organisms, and cross sensitisation in patients.
Tetracyclines should only be used with caution in patients with hepatic dysfunction, lest accumulation occurs with increased toxicity. Careful monitoring of dosage by serum levels is necessary. High dosage of tetracyclines may be hepatotoxic and great care should be used with concurrent administration of other hepatotoxic drugs.
Tetracyclines may cause photosensitivity reactions, manifested by an exaggerated sunburn; however, very rare cases have been reported with lymecycline. Patients should be informed that this reaction may occur and be warned to avoid direct exposure to natural and artificial sunlight and that treatment should be discontinued at the first evidence of skin erythema or skin discomfort.
May cause exacerbation of systemic lupus erythematosus.
Can cause weak neuromuscular blockade so should be used with caution in Myasthenia Gravis.
Tetracyclines are absorbed to some extent by developing bones and teeth and may produce staining and enamel hypoplasia.
Tetracyclines should only be administered with great caution in patients with renal insufficiency lest accumulation occurs with increased toxicity. Dosage may require reduction. High dosage of tetracyclines may be nephrotoxic.
Bulging fontanelles in infants and benign intracranial hypertension in adults has been reported during treatment with tetracyclines. Therefore treatment should cease if evidence of raised intracranial pressure develops during treatment with lymecycline.
Regarding moderate acne vulgaris, lymecycline is indicated only if topical treatment is not effective.
4.5 Interaction with other medicinal products and other forms of interaction
The absorption of tetracyclines may be affected by the simultaneous administration of calcium, aluminium, didanosine, magnesium, bismuth and zinc salts, antacids, Bismuth containing ulcer-healing drugs, iron preparations and quinapril.
The following combinations should therefore be avoided:
Antacids: Antacids containing di- or tri-valent cations form chelate complexes with tetracyclines, resulting in reduced absorption. Sodium bicarbonate has been reported to inhibit the absorption of tetracyclines due to change in pH. Quinapril: Quinapril tablets contain magnesium which forms chelate complexes with tetracycline resulting in reduced absorption.
Didanosine: Didanosine in tablet form contains trivalent cations which form chelate complexes with tetracycline resulting in reduced absorption. There are however no experimental studies.
Combinations where dose adjustment is recommended:
Zinc, calcium, iron: In concomitant treatment, the absorption of tetracyclines is reduced.
These products should not be taken within two to three hours before or after taking lymecycline capsules.
Concomitant use of systemic retinoids including 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 because of their association with rises in blood urea nitrogen levels.
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).
4.6 Fertility, pregnancy and lactation
Pregnancy:
The effect of tetracycline on embryofoetal development in animals has not been reported.
Tetracyclines readily cross the placenta barrier.
Tetracyclines are selectively absorbed by developing bones and teeth and may cause dental staining and enamel hypoplasia. Therefore, lymecycline should not be administered to pregnant women (see section 4.3).
Breastfeeding:
Tetracyclines are distributed into milk.Therefore, lymecycline should not be administered to breast-feeding women (risk of enamel hypoplasia or dental dyschromia in the infant) (see section 4.3).
Fertility:
In humans, the effect of lymecycline on fertility is unknown. In the rat, tetracyclines caused a reduction in the weight of the testis, epididymis and seminal vesicle. In addition a reduction in sperm motility, percentage live spermatozoa and changes in testicular histopathology were noted.
4.7 Effects on ability to drive and use machines
No studies on the effects on the ability to drive and use machines have been performed
4.8 Undesirable effects
The most frequently reported adverse events with lymecycline are gastrointestinal disorders of nausea, abdominal pain, diarrhoea and nervous system disorder of headache.
The most serious adverse events reported with lymecycline are Stevens Johnson syndrome, anaphylactic reaction, angioneurotic oedema and intracranial hypertension.
The following definitions of frequencies are used:
Common (>1/100 to <1/10)
Not known (cannot be estimated from the available data)
|
System Organ Class |
Frequency |
Adverse Reaction |
|
Blood and lymphatic system disorders |
Not known |
Neutropenia Thrombocytopenia |
|
Immune system disorders |
Not known |
Anaphylactic reaction Hypersensitivity Urticaria Angioneurotic oedema |
|
Nervous system disorders |
Common |
Headache |
|
Not known |
Dizziness *Intracranial hypertension | |
|
Eye disorders |
Not known |
Visual disturbance |
|
Gastrointestinal disorders |
Common |
Nausea Abdominal pain Diarrhoea |
|
Not known |
Epigastralgia Glossitis Vomiting Enterocolitis | |
|
Hepatobiliary disorders |
Not known |
Jaundice |
|
Skin and subcutaneous tissues disorders |
Not known |
Erythematous rash Photosensitivity Pruritus Stevens Johnson syndrome |
|
General disorders and administration site conditions |
Not known |
Pyrexia |
|
Investigations |
Not known |
Transaminases increased Blood alkaline phosphatase increased Blood bilirubin increased |
*(N.B. the occurrence of clinical symptoms including visual disturbance or headache should raise the possibility of the diagnosis of cranial hypertension. The treatment should be interrupted if raised intra-cranial pressure is suspected during lymecycline treatment.
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 lymecycline:
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.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme; website: www.mhra.gov.uk/yellowcard
4.9 Overdose
There is no specific treatment, but gastric lavage should be performed as soon as possible. Supportive measure should be instituted as required and a high fluid intake maintained.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Tetracyclines ATC code: J01AA04 Mode of action
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.
Mechanism of resistance
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.
Breakpoints
No breakpoints are listed for Propionibacterium acnes in the current EUCAST tables. Susceptibility to tetracyclines of species relevant to the approved indication
Commonly susceptible species Gram-positive Anaerobes
Propionibacterium acnes (clinicalisolates)*
*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.
5.2 Pharmacokinetic properties
During absorption lymecycline is quickly hydrolysed to active tetracycline and other, inactive, constituents. Free tetracycline, which is quickly absorbed, gives therapeutic serum concentrations (>1microgram/ml) for at least 12 hours. Therapeutic serum concentrations are reached within one hour and maximum serum concentrations (2-3 microgram/ml) are reached within 2-3 hours. Doubling the dose gives 80% increase in serum concentrations.
The serum half-life of lymecycline is approximately 10 hours.
5.3 Preclinical safety data
There are no non-clinical data of relevance to the prescriber which are additional to that already included in other sections of this SmPC
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Silica colloidal, hydrated
Magnesium stearate
Capsule Body:
Titanium dioxide (E171) Gelatine
Capsule Cap:
Indigo carmine (E132) Black iron oxide (E172) Titanium dioxide (E171) Yellow iron oxide (E172) Gelatine
6.2 Incompatibilities
Not applicable
6.3 Shelf life
15 months
6.4 Special precautions for storage
Store below 25 °C
Store in the original package in order to protect from light
6.5 Nature and contents of container
Al/Al blister
Blister: 16, 20, 21, 28, 56 and 100 capsules.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
No special requirements
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
Actavis Group PTC ehf.
Reykjavikurvegi 76-78 220 Hafnarfjordur Iceland
8 MARKETING AUTHORISATION NUMBER(S)
PL 30306/0419
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
21/12/2012
10 DATE OF REVISION OF THE TEXT
12/07/2016