oracea

Important safety information

The use of Doxycycline during tooth development (the second and third trimesters of pregnancy, infancy and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown) and reversible inhibition of bone growth. ( 5.1 , 5.2 , 8.1 , 8.4 ) Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of Clostridium difficile . If C. difficile associated diarrhea occurs, discontinue Doxycycline. ( 5.3 ) If renal impairment exists, Doxycycline doses may need to be adjusted to avoid excessive systemic accumulations of the drug and possible liver injury. ( 5.4 ) Photosensitivity can occur with Doxycycline; Patients should minimize or avoid exposure to natural or artificial sunlight. ( 5.5 ) Tetracyclines have been associated with the development of autoimmune syndromes; if symptoms develop, discontinue Doxycycline immediately. ( 5.6 ) Doxycycline may cause pseudotumor cerebri (benign intracranial hypertension). Discontinue Doxycycline if symptoms occur. ( 5.8 ) Bacterial resistance to tetracyclines may develop in patients using Doxycycline. It should only be used as indicated. ( 5.9 ) 5.1 Inhibition of Bone Growth During Fetal and Pediatric Development Doxycycline, like other tetracycline-class drugs, may cause inhibition of bone growth when administered during the second and third trimesters of pregnancy, infancy, and childhood. All tetracyclines form a stable calcium complex in any bone-forming tissue. A decrease in fibula growth rate has been observed in premature human infants given oral tetracycline in doses of 25 mg/kg every 6 hours. This reaction was shown to be reversible when the drug was discontinued. If doxycycline is used during the second or third trimester of pregnancy, advise the patient of the potential risk to the fetus [ see Use in Specific Populations (8.1 ) ]. 5.2 Tooth Discoloration During Fetal and Pediatric Development The use of tetracycline class drugs orally during tooth development (last half of pregnancy, infancy, and childhood up 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 drug but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Use of tetracycline drugs is not recommended during tooth development [ see Use in Specific Populations (8.1) ]. 5.3 Clostridium difficile Associated Diarrhea (CDAD) Clostridium difficile associated diarrhea (CDAD) has been reported with 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. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate management should be instituted as clinically indicated. 5.4 Metabolic Effects The anti-anabolic action of the tetracyclines may cause an increase in BUN. While this is not a problem in those with normal renal function, in patients with significantly impaired function, higher serum levels of tetracycline-class antibiotics may lead to azotemia, hyperphosphatemia, and acidosis. If renal impairment exists, even usual oral or parenteral doses may lead to excessive systemic accumulations of the drug and possible liver toxicity. Under such conditions, lower than usual total doses are indicated, and if therapy is prolonged, serum level determinations of the drug may be advisable. 5.5 Photosensitivity Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Although this was not observed during the duration of the clinical studies with Doxycycline, patients should minimize or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) while using Doxycycline. If patients need to be outdoors while using Doxycycline, they should wear loose-fitting clothes that protect skin from sun exposure and discuss other sun protection measures with their physician. 5.6 Autoimmune Syndromes Tetracyclines have been associated with the development of autoimmune syndromes. Symptoms may be manifested by fever, rash, arthralgia, and malaise. In symptomatic patients, liver function tests, ANA, CBC, and other appropriate tests should be performed to evaluate the patients. Use of all tetracycline-class drugs should be discontinued immediately. 5.7 Tissue Hyperpigmentation Tetracycline-class drugs are known to cause hyperpigmentation. Tetracycline therapy may induce hyperpigmentation in many organs, including nails, bone, skin, eyes, thyroid, visceral tissue, oral cavity (teeth, mucosa, alveolar bone), sclerae and heart valves. Skin and oral pigmentation has been reported to occur independently of time or amount of drug administration, whereas other pigmentation has been reported to occur upon prolonged administration. Skin pigmentation includes diffuse pigmentation as well as over sites of scars or injury. 5.8 Pseudotumor Cerebri Pseudotumor cerebri (benign intracranial hypertension) in adults has been associated with the use of tetracyclines. The usual clinical manifestations are headache and blurred vision. Bulging fontanels have been associated with the use of tetracyclines in infants. While both of these conditions and related symptoms usually resolve after discontinuation of the tetracycline, the possibility for permanent sequelae exists. Patients should be questioned for visual disturbances prior to initiation of treatment with tetracyclines and should be routinely checked for papiledema while on treatment. 5.9 Development of Drug Resistant Bacteria Bacterial resistance to tetracyclines may develop in patients using Doxycycline. Because of the potential for drug-resistant bacteria to develop during the use of Doxycycline, it should only be used as indicated. 5.10 Superinfection As with other antibiotic preparations, use of Doxycycline may result in overgrowth of non-susceptible microorganisms, including fungi. If superinfection occurs, Doxycycline should be discontinued and appropriate therapy instituted. Although not observed in clinical trials with Doxycycline, the use of tetracyclines may increase the incidence of vaginal candidiasis. Doxycycline should be used with caution in patients with a history of or predisposition to Candida overgrowth. 5.11 Laboratory Monitoring Periodic laboratory evaluations of organ systems, including hematopoietic, renal and hepatic studies should be performed. Appropriate tests for autoimmune syndromes should be performed as indicated. 5.12 Fixed Drug Eruptions Fixed drug eruptions have occurred with doxycycline and have been associated with worsening severity upon subsequent administrations, including generalized bullousfixed drug eruption [see Adverse Reactions (6.2)]. If severe skin reactions occur, discontinue ORACEA immediately and initiate appropriate therapy.