Warnings for Solodyn
Included as part of the PRECAUTIONS section.
Precautions for Solodyn
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, discontinue SOLODYN immediately.
Tooth Discoloration And Enamel Hypoplasia
The use of tetracycline-class drugs, including SOLODYN, 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-grayÂbrown). 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 SOLODYN is not recommended during tooth development.
Advise the patient of the potential risk to the fetus if SOLODYN is used during the second or third trimester of pregnancy [see Use In Specific Populations].
Inhibition Of Bone Growth
The use of tetracycline-class drugs, including SOLODYN, 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 SOLODYN, 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 SOLODYN is used during the second or third trimester of pregnancy [see Use In Specific Populations].
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 SOLODYN.
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 SOLODYN if liver injury is suspected.
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 SOLODYN. These symptoms may disappear during therapy and usually rapidly disappear when SOLODYN is discontinued.
Idiopathic Intracranial Hypertension
Idiopathic intracranial hypertension has been associated with the use of tetracycline-class drugs, including SOLODYN. 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 SOLODYN 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.
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 SOLODYN.
Metabolic Effects
The anti-anabolic action of the tetracyclines, including SOLODYN, 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 SOLODYN, and if therapy is prolonged, monitor serum levels SOLODYN.
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 SOLODYN. Instruct patients to use sunscreen products and wear protective apparel (e.g., hat) when exposure to sun cannot be avoided.
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.
Development Of Drug-Resistant Bacteria
Bacterial resistance to tetracyclines may develop in patients using SOLODYN. Because of the potential for drug-resistant bacteria to develop during the use of SOLODYN, it should be used only as indicated.
Superinfection
Use of SOLODYN may result in overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, discontinue SOLODYN and institute appropriate therapy.
Laboratory Monitoring
Perform periodic laboratory evaluations of organ systems, including hematopoietic, renal, and hepatic studies.
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION).
Patients taking SOLODYN extended-release tablets should receive the following information and instructions:
Administration Instructions
- SOLODYN should be taken exactly as directed.
- Advise patients to swallow SOLODYN extended-release tablets whole and not to chew, crush, or split the tablets [see DOSAGE AND ADMINISTRATION].
Serious Skin/Hypersensitivity Reactions
- Inform patients that serious skin reactions have occurred with the minocycline use in patients with acne. Advise patients to discontinue use of SOLODYN and contact their healthcare provider immediately at the first evidence of skin erythema [see WARNINGS AND PRECAUTIONS].
Tooth Discoloration And Enamel Hypoplasia
- Advise patients that SOLODYN use in pregnancy may cause permanent tooth discoloration of deciduous teeth. Advise patients to discontinue SOLODYN during pregnancy and to inform their healthcare provider right away if they become pregnant during treatment [see WARNINGS AND PRECAUTIONS, Use In Specific Populations].
- Advise caregivers of pediatric patients that SOLODYN use may cause permanent discoloration of deciduous and permanent teeth [see WARNINGS AND PRECAUTIONS, Use In Specific Populations].
Inhibition Of Bone Growth
- Advise patients that SOLODYN use in pregnancy may cause inhibition of fetal bone growth. Advise patients to discontinue SOLODYN during pregnancy and to inform their healthcare provider right away if they become pregnant during treatment [see WARNINGS AND PRECAUTIONS, Use In Specific Populations].
Clostridioides difficile-Associated Diarrhea (Antibiotic-Associated Colitis)
- Advise patients that Clostridioides difficile-associated diarrhea (antibiotic-associated colitis) can occur with minocycline therapy, including SOLODYN. If patients develop watery or bloody stools, advise patients to seek medical attention [see WARNINGS AND PRECAUTIONS].
Hepatotoxicity
- Inform patients about the possibility of hepatotoxicity. Advise patients to seek medical advice if they experience signs or symptoms of hepatotoxicity, including loss of appetite, tiredness, diarrhea, jaundice, bleeding easily, confusion, and sleepiness [see WARNINGS AND PRECAUTIONS].
Central Nervous System Effects
- Inform patients that central nervous system adverse reactions including dizziness or vertigo have been reported with oral minocycline therapy. Caution patients about driving vehicles or using hazardous machinery if they experience such symptoms while on SOLODYN [see WARNINGS AND PRECAUTIONS].
Idiopathic Intracranial Hypertension
- Inform patients that idiopathic intracranial hypertension can occur with minocycline therapy. Advise patients to seek medical attention if they develop unusual headache, visual symptoms, such as blurred vision, diplopia, and vision loss [see WARNINGS AND PRECAUTIONS].
Autoimmune Syndromes
- Inform patients that autoimmune syndromes, including drug-induced lupus-like syndrome, autoimmune hepatitis, vasculitis, and serum sickness have been observed with tetracycline-class drugs, including minocycline. Symptoms may be manifested by arthralgia, fever, rash, and malaise. Advise patients who experience such symptoms to immediately discontinue SOLODYN and seek medical help [see WARNINGS AND PRECAUTIONS].
Photosensitivity
- Inform patients that 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 (i.e., tanning beds or UVA/B treatment) while using SOLODYN. Instruct patients to use sunscreen and wear protective clothing (e.g., hat) over treated areas when exposure to sun cannot be avoided [see WARNINGS AND PRECAUTIONS].
Tissue Hyperpigmentation
- Inform patients that SOLODYN may cause discoloration of skin, scars, teeth, or gums [see WARNINGS AND PRECAUTIONS].
Lactation
- Advise patients that SOLODYN therapy is not recommended during breast feeding for 4 days after the final dose [see Use In Specific Populations].
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment Of Fertility
In a carcinogenicity study in which minocycline HCl was orally administered to male and female rats once daily for up to 104 weeks at dosages up to 200 mg/kg/day, minocycline HCl was associated in both sexes with follicular cell tumors of the thyroid gland, including increased incidences of adenomas, carcinomas and the combined incidence of adenomas and carcinomas in males, and adenomas and the combined incidence of adenomas and carcinomas in females. In a carcinogenicity study in which minocycline HCl was orally administered to male and female mice once daily for up to 104 weeks at dosages up to 150 mg/kg/day, exposure to minocycline HCl did not result in a significantly increased incidence of neoplasms in either males or females.
Minocycline was not mutagenic in vitro in a bacterial reverse mutation assay (Ames test) or CHO/HGPRT mammalian cell assay in the presence or absence of metabolic activation. Minocycline was not clastogenic in vitro using human peripheral blood lymphocytes or in vivo in a mouse micronucleus test.
Male and female reproductive performance in rats was unaffected by oral doses of minocycline of up to 300 mg/kg/day (40 times the MRHD on an AUC comparison basis). However, oral administration of 100 or 300 mg/kg/day of minocycline to male rats (15 to 40 times the MRHD on an AUC comparison basis) adversely affected spermatogenesis. Effects observed at 300 mg/kg/day included a reduced number of sperm cells per gram of epididymis, an apparent reduction in the percentage of sperm that were motile, and (at 100 and 300 mg/kg/day) increased numbers of morphologically abnormal sperm cells. Morphological abnormalities observed in sperm samples included absent heads, misshapen heads, and abnormal flagella.
Use In Specific Populations
Pregnancy
Risk Summary
Tetracycline class drugs, including SOLODYN may cause permanent discoloration of deciduous teeth and reversible inhibition of bone growth when administered during the second and third trimesters of pregnancy [see WARNINGS AND PRECAUTIONS and Use In Specific Populations]. A few postmarketing cases of limb reductions have been reported over decades of use; however, the association is unclear. The limited data from postmarketing reports are not sufficient to inform a drug-associated risk for birth defects or miscarriage.
In animal reproduction studies conducted in pregnant rats and rabbits, fetuses with bent limb bones were observed following oral administration of minocycline during organogenesis at systemic exposures 3 and 2 times, respectively, the exposure associated with the maximum recommended human dose (MRHD) (see Data).
If a patient becomes pregnant while taking this drug, advise the patient of the risk to the fetus and to discontinue treatment.
The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data
Human Data
The use of tetracycline class drugs, including SOLODYN, during tooth development (second and third trimesters of pregnancy, infancy, and childhood up to the age of 8 years) may cause permanent discoloration of deciduous teeth (yellow-gray-brown). Permanent discoloration of the teeth is more common during long-term use of the drug but has been observed following repeated short-term courses [see WARNINGS AND PRECAUTIONS].
Animal Data
Results of animal studies indicate that tetracyclines cross the placenta, are found in fetal tissues, and can cause delayed skeletal development in the developing fetus. Evidence of embryotoxicity has been noted in animals treated early in pregnancy [see WARNINGS AND PRECAUTIONS].
Minocycline induced skeletal malformations (bent limb bones) in fetuses when administered to pregnant rats and rabbits during the period of organogenesis at doses of 30 mg/kg/day and 100 mg/kg/day, respectively (3 times the MRHD and 2 times the MRHD on an AUC comparison basis, respectively). Reduced mean fetal body weight was observed in studies in which minocycline was administered to pregnant rats at an oral dose of 10 mg/kg/day (approximately equal to the MRHD on an AUC comparison basis).
Minocycline was assessed for effects on peri- and post-natal development of rats in a study that involved oral administration to pregnant rats during the period of organogenesis through lactation at dosages of 5, 10, or 50 mg/kg/day. In this study, body weight gain was significantly reduced in pregnant females that received 50 mg/kg/day (2.5 times the MRHD on an AUC comparison basis). No effects of treatment on the duration of the gestation period or the number of live pups born per litter were observed. Gross external anomalies observed in offspring of animals that received minocycline included reduced body size, improperly rotated forelimbs, and reduced size of extremities. No effects were observed on the physical development, behavior, learning ability, or reproduction of the offspring of animals that received minocycline.
Lactation
Risk Summary
Tetracycline-class antibiotics, including minocycline, are present in breast milk following oral administration. There are no data on the effects of minocycline on milk production. Because of the potential for serious adverse reactions, including tooth discoloration and inhibition of bone growth, advise patients that breastfeeding is not recommended during SOLODYN therapy and for 4 days after the final dose [see WARNINGS AND PRECAUTIONS].
Pediatric Use
The safety and effectiveness of SOLODYN have been established in pediatric patients 12 years of age and older for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris [see Clinical Studies]. Tooth discoloration and inhibition of bone growth have been observed in pediatric patients [see WARNINGS AND PRECAUTIONS]. Use of tetracycline-class antibiotics below the age of 8 is not recommended due to the potential for tooth discoloration [see WARNINGS AND PRECAUTIONS].
Safety and effectiveness of SOLODYN have not been established in pediatric patients younger than 12 years of age.
Geriatric Use
Clinical studies of SOLODYN did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.