Doxycycline hyclate warnings and precautions

# Warnings and Precautions

## Warnings
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 DISCOLORATION OF THE TEETH (YELLOW-GRAY-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.  TETRACYCLINE DRUGS, THEREFORE, SHOULD NOT BE USED IN THIS AGE GROUP, EXCEPT FOR ANTHRAX, INCLUDING INHALATIONAL ANTHRAX (POST-EXPOSURE), UNLESS OTHER DRUGS ARE NOT LIKELY TO BE EFFECTIVE OR ARE CONTRAINDICATED.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including doxycycline, and may range in severity from mild to life-threatening.  Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.
Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of clostridia.  Studies indicate that a toxin produced by Clostridium difficile is a primary cause of antibiotic-associated colitis.
After the diagnosis of pseudomembranous colitis has been established, therapeutic measures should be initiated.  Mild cases of pseudomembranous colitis usually respond to discontinuation of the drug alone.  In moderate to severe cases, consideration should be given to management with fluids and electrolytes, protein supplementation, and treatment with an antibacterial drug clinically effective against Clostridium difficile colitis.
Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines.  Patients apt 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.
The anti-anabolic action of the tetracyclines may cause an increase in BUN.  Studies to date indicate that this does not occur with the use of doxycycline in patients with impaired renal function.
Use in Pregnancy
(See above WARNINGS about use during tooth development).
Doxycycline for injection has not been studied in pregnant patients.  It should not be used in pregnant women unless, in the judgment of the physician, it is essential for the welfare of the patient.
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.
Usage in Children
The use of doxycycline for injection in children under 8 years is not recommended because safe conditions for its use have not been established.  (See above WARNINGS about use during tooth development).
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.
Tetracyclines are present in the milk of lactating women who are taking a drug in this class.

## Precautions
Prescribing doxycycline in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
As with other antibiotic preparations, use of this drug may result in overgrowth of nonsusceptible organisms, including fungi.  If superinfection occurs, the antibiotic should be discontinued and appropriate therapy instituted.
In venereal diseases when coexistent syphilis is suspected, a dark field examination should be done before treatment is started and the blood serology repeated monthly for at least four months.
Because tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.
In long-term therapy, periodic laboratory evaluation of organ systems, including hematopoietic, renal and hepatic studies should be performed.
All infections due to group A beta-hemolytic streptococci should be treated for at least 10 days.
Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracycline in conjunction with penicillin.
Pregnancy: Teratogenic Effects: Pregnancy Category D
There are no adequate and well-controlled studies on the use of doxycycline in pregnant women.  The vast majority of reported experience with doxycycline during human pregnancy is short-term, first trimester exposure.  There are no human data available to assess the effects of long-term therapy of doxycycline in pregnant women such as that proposed for treatment of anthrax exposure.  An expert review of published data on experiences with doxycycline use during pregnancy by TERISthe Teratogen Information Systemconcluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (the quantity and quality of data were assessed as limited to fair), but the data are insufficient to state that there is no risk.1
A case-control study (18,515 mothers of infants with congenital anomalies and 32,804 mothers of infants with no congenital anomalies) shows a weak but marginally statistically significant association with total malformations and use of doxycycline anytime during pregnancy.  (Sixty-three (0.19%) of the controls and 56 (0.30%) of the cases were treated with doxycycline).  This association was not seen when the analysis was confined to maternal treatment during the period of organogenesis (i.e., in the second and third months of gestation) with the exception of a marginal relationship with neural tube defect based on only two exposed cases.2
A small prospective study of 81 pregnancies describes 43 pregnant women treated for 10 days with doxycycline during early first trimester.  All mothers reported their exposed infants were normal at 1 year of age.3
Nursing Mothers
Tetracyclines are excreted in human milk, however, the extent of absorption of tetracyclines, including doxycycline, by the breastfed infant is not known.  Short-term use by lactating women is not necessarily contraindicated; however, the effects of prolonged exposure to doxycycline in breast milk are unknown.4  Because of the potential for adverse reactions in nursing infants from doxycycline, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother (see WARNINGS).
Information for Patients
Patients should be counseled that antibacterial drugs including doxycycline should only be used to treat bacterial infections.  They do not treat viral infections (e.g., the common cold).  When doxycycline is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed.  Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by doxycycline or other antibacterial drugs in the future.