MINOCYCLINE HYDROCHLORIDE

Serious Skin/Hypersensitivity Reactions: Minocycline has been associated with anaphylaxis, serious skin reactions, erythema multiforme, and drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. Discontinue immediately if symptoms occur. ( 5.1 ) Tooth Discoloration and Enamel Hypoplasia: Use during 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). ( 5.2 , 8.1 , 8.4 ) Inhibition of Bone Growth: Use during the second and third trimesters of pregnancy, infancy, and childhood up to the age of 8 years may cause reversible inhibition of bone growth. ( 5.3 , 8.1 , 8.4 ) Clostridioides difficile-Associated Diarrhea (Antibiotic-Associated Colitis): Discontinue if Clostridioides difficile-associated diarrhea (antibiotic-associated colitis) occurs. ( 5.4 ) Hepatotoxicity: Discontinue if liver injury is suspected. ( 5.5 ) Central Nervous System Effects: May cause central nervous system side effects including light-headedness, dizziness, or vertigo. ( 5.6 ) Idiopathic Intracranial Hypertension: May cause idiopathic intracranial hypertension in adults and adolescents. Discontinue if symptoms occur. ( 5.7 ) Autoimmune Syndromes: Minocycline has been associated with autoimmune syndromes; discontinue immediately if symptoms occur. ( 5.8 ) Metabolic Effects: If renal impairment exists, reduce minocycline hydrochloride extended-release tablets dosage. ( 5.9 ) 5.1 Serious Skin/Hypersensitivity Reactions Cases of anaphylaxis, serious skin reactions (e.g., Stevens-Johnson syndrome), erythema multiforme, and drug rash with eosinophilia and systemic symptoms (DRESS) syndrome have been reported postmarketing with minocycline use in patients with acne. DRESS syndrome consists of cutaneous reaction (such as rash or exfoliative dermatitis), eosinophilia, and one or more of the following visceral complications such as: hepatitis, pneumonitis, nephritis, myocarditis, and pericarditis. Fever and lymphadenopathy may be present. In some cases, death has been reported. If this syndrome is recognized, minocycline hydrochloride extended-release tablets should be discontinued immediately. Fixed drug eruptions have occurred with minocycline and other tetracyclines. Worsening severity upon subsequent administrations, including generalized bullous fixed drug eruption, has been observed with other tetracyclines [see ADVERSE REACTIONS ( 6.2 )] . If severe skin/hypersensitivity reactions occur, discontinue minocycline hydrochloride extended-release tablets and institute appropriate therapy. 5.2 Tooth Discoloration and Enamel Hypoplasia The use of tetracycline-class drugs, including minocycline hydrochloride extended-release tablets, during tooth development (second and third trimesters of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of the teeth (yellow-graybrown). Permanent discoloration of the teeth is more common during long-term use of tetracycline-class drugs but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Use of minocycline hydrochloride extended-release tablets is not recommended during tooth development. Advise the patient of the potential risk to the fetus if minocycline hydrochloride extended-release tablets is used during the second or third trimester of pregnancy [see Use in Specific Populations ( 8.1 , 8.4 )]. 5.3 Inhibition of Bone Growth The use of tetracycline-class drugs, including minocycline hydrochloride extended-release tablets, during the second and third trimesters of pregnancy, infancy, and childhood up to the age of 8 years may cause reversible inhibition of bone growth. All tetracyclines, including minocycline hydrochloride extended-release tablets, 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. Advise the patient of the potential risk to the fetus if minocycline hydrochloride extended-release tablets is used during the second or third trimester of pregnancy [see Use in Specific Populations ( 8.1 , 8.4 )]. 5.4 Clostridioides difficile Associated Diarrhea (Antibiotic Associated Colitis) Clostridioides difficile -associated diarrhea (CDAD) has been reported with nearly all antibacterial agents, including minocycline, and may range in severity from mild diarrhea to fatal colitis. 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, discontinue minocycline hydrochloride extended-release tablets. 5.5 Hepatotoxicity Postmarketing cases of serious liver injury, including irreversible drug-induced hepatitis and fulminant hepatic failure (sometimes fatal), have been reported with minocycline use in the treatment of acne. Discontinue minocycline hydrochloride extended-release tablets if liver injury is suspected. 5.6 Central Nervous System Effects Central nervous system side effects including light-headedness, dizziness, or vertigo have been reported with minocycline therapy. Caution patients who experience these symptoms about driving vehicles or using hazardous machinery while on minocycline hydrochloride extended-release tablets. These symptoms may disappear during therapy and usually rapidly disappear when minocycline hydrochloride extended-release tablets is discontinued. 5.7 Idiopathic Intracranial Hypertension Idiopathic intracranial hypertension has been associated with the use of tetracycline-class drugs, including minocycline hydrochloride extended-release tablets. Clinical manifestations of idiopathic intracranial hypertension include headache, blurred vision, diplopia, and vision loss; papilledema can be found on fundoscopy. Women of childbearing age who are overweight or have a history of idiopathic intracranial hypertension are at a greater risk for developing idiopathic intracranial hypertension. Avoid concomitant use of isotretinoin and minocycline hydrochloride extended-release tablets because isotretinoin, a systemic retinoid, is also known to cause idiopathic intracranial hypertension. Permanent visual loss may exist, even after the medication is discontinued. If visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted. Because intracranial pressure can remain elevated for weeks after drug cessation, monitor patients until they stabilize. 5.8 Autoimmune Syndromes Tetracyclines have been associated with the development of autoimmune syndromes. The long-term use of minocycline in the treatment of acne has been associated with drug-induced lupus-like syndrome, autoimmune hepatitis, and vasculitis. Sporadic cases of serum sickness have presented shortly after minocycline use. Symptoms may be manifested by fever, rash, arthralgia, and malaise. Evaluate symptomatic patients. If symptoms occur, immediately discontinue use of minocycline hydrochloride extended-release tablets. 5.9 Metabolic Effects The anti-anabolic action of the tetracyclines, including minocycline hydrochloride extended-release tablets, may cause an increase in blood urea nitrogen (BUN). In patients with significantly impaired renal function, higher serum levels of tetracycline-class drugs may lead to azotemia, hyperphosphatemia, and acidosis. If renal impairment exists, lower the total doses of minocycline hydrochloride extended-release tablets, and if therapy is prolonged, monitor serum levels minocycline hydrochloride extended-release tablets. 5.10 Photosensitivity Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines, including minocycline. Advise patients to minimize or avoid exposure to natural or artificial sunlight (e.g., tanning beds or UVA/B treatment) while using minocycline hydrochloride extended-release tablets. Instruct patients to use sunscreen products and wear protective apparel (e.g., hat) when exposure to sun cannot be avoided. 5.11 Tissue Hyperpigmentation Tetracycline-class antibiotics are known to cause hyperpigmentation. Tetracycline therapy may induce hyperpigmentation in many organs, including nails, bone, skin, eyes, thyroid, visceral tissue, oral cavity (e.g., 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 tissue pigmentation has been reported to occur upon prolonged administration. Skin pigmentation includes diffuse pigmentation as well as over sites of scars or injury. 5.12 Development of Drug-Resistant Bacteria Bacterial resistance to tetracyclines may develop in patients using minocycline hydrochloride extended-release tablets. Because of the potential for drug-resistant bacteria to develop during the use of minocycline hydrochloride extended-release tablets, it should be used only as indicated. 5.13 Superinfection Use of minocycline hydrochloride extended-release tablets may result in overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, discontinue minocycline hydrochloride extended-release tablets and institute appropriate therapy. 5.14 Laboratory Monitoring Perform periodic laboratory evaluations of organ systems, including hematopoietic, renal, and hepatic studies.