VIBRAMYCIN Capsule, Tablet Ref.[50938] Active ingredients: Doxycycline

Use in Children

As with other tetracyclines, doxycycline forms a stable calcium complex in any bone-forming tissue. A decrease in the fibula growth rate has been observed in prematures given oral tetracycline in doses of 25 mg/kg every six hours. This reaction was shown to be reversible when the drug was discontinued.

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 pediatric patients 8 years of age or less only when the potential benefits are expected to outweigh the risks in severe or life-threatening conditions (e.g., anthrax, Rocky Mountain spotted fever), particularly when there are no alternative therapies.7

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 Undesirable effects). If severe skin reactions occur, doxycycline should be discontinued immediately and appropriate therapy should be instituted.8

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).3

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 diarrhea subsequent to the administration of antibacterial agents.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including doxycycline, and may range in severity from mild diarrhea 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 diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

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

Instances of esophagitis and esophageal ulcerations have been reported in patients receiving capsule and tablet forms of drugs in the tetracycline class, including doxycycline. Most of these patients took medications immediately before going to bed.

The anti-anabolic action of tetracyclines may cause an increase in BUN. Studies to date indicate that this antianabolic effect does not occur with the use of doxycycline in patients with impaired renal function.

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

In long-term therapy, periodic laboratory evaluation of organ systems, including hematopoietic, renal and hepatic studies should be performed.

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.

When treating venereal disease when 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 four months.

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

Information for Patients

All patients taking doxycycline should be advised:

• To avoid excessive sunlight or artificial ultraviolet light while receiving doxycycline and to discontinue therapy if phototoxicity (e.g., skin eruption, etc.) occurs. Sunscreen or sunblock should be considered.
• To drink fluids liberally along with doxycycline to reduce the risk of esophageal irritation and ulceration.
• That the absorption of tetracyclines is reduced when taking bismuth subsalicylate.
• That the use of doxycycline might increase the incidence of vaginal candidiasis.

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 doxycycline in conjunction with penicillin.

Absorption of tetracyclines is impaired by antacids containing aluminum, calcium, magnesium or other drugs containing these cations, iron-containing preparations and bismuth salts.

Alcohol, barbiturates, carbamazepine and phenytoin decrease the half-life of doxycycline.

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

Concurrent use of tetracyclines may render oral contraceptives less effective.

Laboratory Test Interactions

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

Use in Pregnancy

Doxycycline has not been studied in pregnant patients. It should not be used in pregnant women unless, in the judgment of the physician, the potential benefit outweighs the risk (see section 4.4 Special Warnings and Precautions for Use: Use in Children).

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.

Lactation

As with other tetracyclines, doxycycline forms a stable calcium complex in any bone-forming tissue. A decrease in the fibula growth rate has been observed in prematures given oral tetracycline in doses of 25 mg/kg every six hours. This reaction was shown to be reversible when the drug was discontinued (see section 4.4 Special Warnings and Precautions for Use: Use in Children).

Doxycycline should be avoided in nursing mothers, as tetracyclines including doxycycline are present in the milk of lactating women who are taking a drug of this class.

The effect of doxycycline on the ability to drive or 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.

^a Reversible and superficial discolouration of permanent teeth has been reported with the use of doxycycline
^b in the setting of spirochete infections treated with doxycycline.
^c with chronic use of doxycycline

Not available.