REMYCIN Hard capsule Ref.[28312] Active ingredients: Doxycycline

Paediatric population

The use of drugs of the tetracycline class during tooth development (last half of pregnancy; infancy and childhood to the age of 8 years) may cause permanent discolouration of the teeth (yellow-grey-brown). This adverse reaction is more common during long-term use of the drugs but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Use doxycycline in paediatric patients aged younger than 8 years only when the potential benefits are expected to outweigh the risks in severe or life-threatening conditions (e.g. Rocky Mountain spotted fever), only when there are no adequate alternative therapies.

Although the risk of permanent teeth staining is rare in children aged 8 years to less than 12 years, the use of doxycycline should be carefully justified in situations where other drugs are not available, are not likely to be effective or are contraindicated.

Use in Patients with Impaired Hepatic Function

Remycin should be administered with caution to patients with hepatic impairment or those receiving potentially hepatotoxic drugs.

Abnormal hepatic function has been reported rarely and has been caused by both the oral and parenteral administration of tetracyclines, including doxycycline.

Use in Patients with Renal Impairment

Excretion of doxycycline by the kidney is about 40%/72 hours in individuals with normal renal function. This percentage excretion may fall to a range as low as 1-5%/72 hours in individuals with severe renal insufficiency (creatinine clearance below 10 ml/min). Studies have shown no significant difference in the serum half-life of doxycycline in individuals with normal and severely impaired renal function. Haemodialysis does not alter the serum half-life of doxycycline. The anti-anabolic action of the tetracyclines may cause an increase in blood urea. Studies to date indicate that this anti-anabolic effect does not occur with the use of Remycin in patients with impaired renal function.

General

Severe skin reactions, such as exfoliative dermatitis, erythema multiforme, Stevens- Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in patients receiving doxycycline (see section 4.8). If severe skin reactions occur, doxycycline should be discontinued immediately and appropriate therapy should be instituted.

Photosensitivity

Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines, including doxycycline. Patients likely to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracycline drugs and treatment should be discontinued at the first evidence of skin erythema.

Microbiological overgrowth

The use of antibiotics may occasionally result in over-growth of non-susceptible organisms. Constant observation of the patient is essential. If a resistant organism appears, the antibiotic should be discontinued and appropriate therapy instituted.

General

Benign intracranial hypertension (pseudotumor cerebri) has been associated with the use of tetracyclines including doxycycline. Benign intracranial hypertension (pseudotumor cerebri) is usually transient, however cases of permanent visual loss secondary to benign intracranial hypertension (pseudotumor cerebri) have been reported with tetracyclines including doxycycline. If visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted. Since intracranial pressure can remain elevated for weeks after drug cessation patients should be monitored until they stabilize. Concomitant use of isotretinoin and doxycycline should be avoided because isotretinoin is also known to cause benign intracranial hypertension (pseudotumor cerebri).

Pseudomembranous colitis has been reported with nearly all antibacterial agents, including doxycycline, and has ranged in severity from mild to life-threatening. It is important to consider this diagnosis in patients who present with diarrhoea subsequent to the administration of antibacterial agents.

Clostridium difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including doxycycline, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

Oesophagitis

Cases of oesophageal injuries (oesophagitis and ulceration), sometimes serious, have been reported. Patients should be instructed to take doxycycline capsules with plenty of water (at least 100 ml), remain upright and not take their treatment before going to bed (see section 4.2). Withdrawal of doxycycline and investigation of oesophageal disorder should be considered if symptoms such as dyspepsia or retrosternal pain occur. Caution is required in the treatment of patients with known oesophageal reflux disorders.

Venereal disease

When treating venereal disease, where co-existent syphilis is suspected, proper diagnostic procedures, including dark-field examinations should be utilised. In all such cases monthly serological tests should be made for at least four months.

Beta-haemolytic streptococci infections

Infections due to a group A beta-haemolytic streptococci should be treated for at least 10 days.

Jarisch-Herxheimer reaction

Some patients with spirochete infections may experience a Jarisch-Herxheimer reaction shortly after doxycycline treatment is started. Patients should be reassured that this is a usually self-limiting consequence of antibiotic treatment of spirochete infections.

Myasthenia gravis

Due to a potential for weak neuromuscular blockade, care should be taken in administering tetracyclines to patients with myasthenia gravis.

This product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

This medicine contains sodium. This medicine contains less than 1 mmol sodium (23 mg) per capsule, that is to say essentially ‘sodium-free’.

There have been reports of prolonged prothrombin time in patients taking warfarin and doxycycline. Because the tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.

Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving Remycin in conjunction with penicillin.

The absorption of doxycycline is impaired by concurrently administered antacids containing aluminium, calcium, magnesium or other drugs containing these cations; oral zinc, iron salts or bismuth preparations.

The serum half-life of doxycycline is shortened when patients are concurrently receiving alcohol, barbiturates, carbamazepine or phenytoin.

A few cases of pregnancy or breakthrough bleeding have been attributed to the concurrent use of tetracyclines with oral contraceptives.

The concurrent use of tetracyclines and methoxyflurane has been reported to result in fatal renal toxicity.

Laboratory test interactions

False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test.

Pregnancy

Remycin has not been studied in pregnant patients. It should not be used in pregnancy unless, in the judgement of the physician, it is essential for the welfare of the patient (see section 4.3 about use during tooth development).

Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues and can have toxic effects on the developing fetus (often related to retardation of skeletal development). Evidence of embryotoxicity has also been noted in animals treated early in pregnancy.

Breast-feeding

Tetracyclines are present in the milk of lactating women who are taking a drug of this kind and should therefore not be used in nursing mothers (see section 4.3 about use during tooth development).

The effect of doxycycline on the ability to drive and operate heavy machinery has not been studied. There is no evidence to suggest that doxycycline may affect these abilities.

The following adverse reactions have been observed in patients receiving tetracyclines, including doxycycline.

CIOMS III categories: Common ≥1/100 to <1/10 (≥1% and <10%), Uncommon ≥1/1,000 to <1/100 (≥0.1% and <1%), Rare ≥1/10,000 to <1/1,000 (≥0.01% and <0.1%), Not known (frequency cannot be estimated from the available data)
^a Reversible and superficial discolouration of permanent teeth has been reported with the use of doxycycline but frequency cannot be estimated from available data
^b in the setting of spirochete infections treated with doxycycline.
^c with chronic use of doxycycline.

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 national reporting system.

Cyprus: Pharmaceutical Services, Ministry of Health, CY-1475 Nicosia, Fax: +357 22608649, Website: www.moh.gov.cy/phs

Not applicable.