Lymecycline 408 mg Capsules, hard

Lymecycline 408 mg Capsule, hard is indicated for the treatment of infections caused by tetracycline sensitive organisms (please see section 4.4 and 5.1) including the following:

• Acne, moderate to severe.

• Acute sinusitis.

• Acute exacerbation of chronic bronchitis.

• Helicobacter pylori infection.

• Urogenital infections caused by Chlamydia trachomatis.

• Trachoma.

• Rickettsial fever.

• Soft tissue infection.

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Posology

Adults:

The usual dosage for the chronic treatment of acne is 1 capsule (408 mg) daily; treatment should be continued for at least eight (8) weeks.

For other infections, the usual dosage is one capsule (408 mg) twice a day. In the event higher doses are required, 3 – 4 capsules (1224 mg – 1632 mg) may be given over 24 hours.

In the management of sexually transmitted disease, both partners should be treated.

Elderly:

As for other tetracyclines, no specific dosage adjustment is required.

Renal impairment:

Lymecycline is contraindicated in patients with overt renal insufficiency (see section 4.3).

Hepatic impairment:

Use with caution; potential for accumulation with increased toxicity (see section 4.4).

Paediatric population:

The safety and efficacy of Lymecycline 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 section 4.3.

Method of administration

Lymecycline 408 mg capsule, hard are for oral administration.

The capsules should always be taken with a glass of water.

• Hypersensitivity to the active substance or any other tetracycline, or to any of the excipients listed in section 6.1.

• Its use is contraindicated in patients with overt renal insufficiency and in children less than 8 years due to the risk of permanent dental staining and enamel hypoplasia

Concurrent treatment with oral retinoids (see Interaction with other Medications).

Oesophageal irritation and ulceration

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 (see section Posology and method of administration).

Caution should be exercised if the product is administered to patients with impaired renal or hepatic functions.

Hepatotoxicity

Overdosage could result in hepatotoxicity

Antibiotic resistance

Prolonged use of broad spectrum antibiotics may result in the appearance of resistant organisms and superinfection.

Phototoxicity

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.

Expired medication

The use of expired tetracyclines can lead to renal tubular acidosis (Pseudo-Fanconi syndrome) readily reversible when treatment is discontinued altogether.

Systemic lupus erythematosus

May cause exacerbation of systemic lupus erythematosus.

Myasthenia Gravis

Can cause weak neuromuscular blockade so should be used with caution in Myasthenia Gravis.

Hepatic impairment

Care should be exercised in administering tetracyclines to patients with hepatic impairment.

Paediatric population

The product should not be used in children below 12 years of age due to the risk of permanent dental staining and enamel hypoplasia (see Contraindications).

Excipients

This medicinal product contains Tartrazine, E 102, 0.066 mg / capsule: this may cause allergic reactions.

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. 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. These products should not be taken within two (2) hours before or after after taking Lymecycline 408 mg capsules hard.

Some adverse effects are reported with tetracycline therapy in general in case of combination with lithium; an interaction between lithium and the tetracycline class is a recognised interaction. A combination of lymecycline with lithium may cause an increase in serum lithium levels.

Unlike earlier tetracyclines, the absorption of Lymecycline is not significantly impaired by moderate amounts of milk.

Concomitant usage of oral retinoids and vitamin A (above 10 000 IU/day) should be avoided as this may increase the risk of benign intracranial hypertension. An increase in the effects of anticoagulants may occur with tetracyclines with an increased risk of haemorrhage. Concomitant use of diuretics should be avoided.

Bacteriostatic medicinal products including lymecycline may interfere with the bacteriocidal action of penicillin and beta-lactam antibiotics. It is advisable that tetracycline-class drugs and penicillin should not therefore be used in combination.

Tetracyclines and methoxyflurane used in combination have been reported to result in fatal renal toxicity.

Paediatric population

Interaction studies have only been performed in adults.

Tetracyclines are selectively absorbed by developing bones and teeth and may cause dental dyschromia and enamel hypoplasia (see section 4.3).

Pregnancy:

Tetracyclines readily cross the placental barrier. Therefore, Lymecycline should not be administered to pregnant women.

Breast-feeding:

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:

No data on the effect on fertility is available.

No studies on the effects on the ability to drive and use machines have been performed.

Tabulated list of adverse reactions

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.

Adverse reactions are ranked by frequency, the most frequent first, 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) and

Not known (cannot be estimated from the available data).

Description of selected adverse reactions

Benign intracranial hypertension and bulging fontanelles in infants were reported with tetracyclines with possible symptoms of headaches, vomiting, 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 eight (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 staphylococcal 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 at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Symptoms

Acute overdosage is rare with antibiotics and there is no specific treatment.

Management

Supportive measures should be instituted, as required and a high fluid intake maintained.

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. The mechanism of action is based on an inhibition of ribosomal protein synthesis. Tetracyclines block access of the bacterial aminoacyl – t RNA 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 effects is limited to the bacterial cells.

The exact mechanism of action by which tetracyclines reduce lesions of acne vulgaris has not been fully elucidated; 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 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, i.e papules, pustules, nodules, cysts, of acne. However, other mechanisms also appear to be involved because e 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:

For tetracycline resistance in anaerobic and most aerobic bacteria, the breakpoints as set by the NCCLS are:

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 infection is questionable.

Susceptibility to tetracyclines of species relevant to the approved indications:

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 gastrointestinal tract than tetracycline, with peak serum concentrations 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.

No specific information is presented given the vast experience gained with the use of tetracyclines in humans over the last forty years.

Environmental Risk Assessment (ERA):

This is a generic medicinal product, containing lymecycline. As such, it will simply replace already existing products in the market, without leading to additional prescribing and usage of lymecycline. As such it will not result in any additional environmental exposure to lymecycline, or the in vitro produced tetracycline. Therefore, there is no requirement for any additional environmental risk assessment.

Capsule contents:

Colloidal anhydrous silica

Magnesium stearate

Capsule cap:

Gelatin

Indigo carmine, E 132

Erythrosine, E 127

Titanium dioxide, E 171

Capsule body:

Gelatin

Tartrazine, E 102

Titanium dioxide, E 171

Not applicable.

2 years

Store below 25°C.

Store in the original package.

Aluminium (Al) – Aluminium (Al) blister strips.

Packs containing 7, 14, 28, 56, and 112 capsules.

Not all pack sizes may be marketed.

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.