Minocycline Hydrochloride Extended-Release

5 WARNINGS AND PRECAUTIONS 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 EMROSI immediately if symptoms occur. ( 5.1 ) Tooth Discoloration and Enamel Hypoplasia: The use of EMROSI 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-gray-brown). ( 5.2 ) 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 ) Clostridioides difficile -Associated Diarrhea (Antibiotic-Associated Colitis): Discontinue if Clostridioides difficile -associated diarrhea (antibiotic-associated colitis) occurs. ( 5.4 ) Hepatotoxicity: Discontinue EMROSI 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 EMROSI if symptoms occur. ( 5.7 ) Autoimmune Syndromes: Minocycline has been associated with autoimmune syndromes; discontinue EMROSI immediately if symptoms occur. ( 5.8 ) Metabolic Effects: If renal impairment exists, monitor serum levels of EMROSI during treatment, discontinue EMROSI if necessary. ( 5.9 ) 5.1 Hypersensitivity Reaction and Serious Skin 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, discontinue EMROSI immediately. 5.2 Tooth Discoloration and Enamel Hypoplasia The use of tetracycline class drugs, including EMROSI 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-gray-brown). 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 EMROSI is not recommended during tooth development. Advise the patient of the potential risk to the fetus if EMROSI 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 EMROSI, 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 EMROSI, 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 EMROSI 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) Clostridium 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 EMROSI. 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 EMROSI 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 EMROSI. These symptoms may disappear during therapy and usually rapidly disappear when the drug is discontinued. 5.7 Idiopathic Intracranial Hypertension Idiopathic Intracranial hypertension has been associated with the use of tetracyclines. 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 EMROSI 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 EMROSI. 5.9 Metabolic Effects The anti-anabolic action of the tetracyclines, including EMROSI, may cause an increase in blood urea nitrogen (BUN). In patients with significantly impaired renal function, higher serum levels of EMROSI may lead to azotemia, hyperphosphatemia, and acidosis. If renal impairment exists, monitor serum levels of EMROSI during treatment, and discontinue EMROSI if necessary. 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 (tanning beds or UVA/B treatment) while using EMROSI. 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. EMROSI 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 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 the tetracyclines may develop in patients using EMROSI, Because of the potential for drug-resistant bacteria to develop during the use of EMROSI, use EMROSI only as indicated. 5.13 Superinfection Use of EMROSI may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, discontinue EMROSI and institute appropriate therapy. 5.14 Laboratory Monitoring Perform periodic laboratory evaluations of organ systems, including hematopoietic, renal and hepatic studies.