Special Warning : אזהרת שימוש

4.4. Special Warnings and Precautions for Use

Use in patients with impaired hepatic function: Doxylin 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 10ml/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 doxycycline 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. All patients taking doxycycline should be advised to avoid excessive sunlight or artificial ultraviolet light while receiving 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. Sunscreen or sunblock should be considered.
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. Women of childbearing age who are overweight or have a history of IH are at greater risk for developing tetracycline associated IH. 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 tablets with plenty of water (at least 100ml), 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 utilized. In all such cases monthly serological tests should be made for at least 4 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.
Systemic lupus erythematosus: Tetracyclines can cause exacerbation of SLE (see section 4.8).
Plasmodium strains: Doxycycline offers substantial but not complete suppression of the asexual blood stages of Plasmodium strains.
Doxycycline does not suppress P. falciparum’s sexual blood stage gametocytes. Subjects completing this prophylactic regimen may still transmit the infection to mosquitoes outside endemic areas.


Laboratory Tests
In venereal disease, when co-existent syphilis is suspected, dark field examinations should be done before treatment is started and the blood serology repeated monthly for at least 4 months.
In long-term therapy, periodic laboratory evaluation of organ systems, including hematopoietic, renal, and hepatic studies, should be performed.

Excipient information
• Doxylin contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.
•   Doxylin contains the excipient Sunset Yellow FCF Aluminum Lake (E110), which may cause allergic reactions.

Effects on Driving

4.7 Effects on Ability to Drive and Use Machines
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.