Sarecycline is a tetracycline-class antibiotic indicated for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in patients 9 years of age and older. The efficacy of sarecycline was established in 2 clinical trials in patients with acne. At 12 weeks, a significantly higher proportion of sarecycline-treated patients had improved acne and a reduction in inflammatory acne lesions compared with placebo. As with other tetracyclines, sarecycline should not be used in pediatric patients younger than 8 years due to the potential for permanent tooth discoloration and decay if used during tooth development.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Administer with or without food.
-Administer with adequate amounts of fluid to reduce the risk of esophageal irritation and ulceration.
-Divalent and trivalent cations significantly affect absorption. Separate administration of sarecycline from antacids containing aluminum, calcium, or magnesium, sucralfate, bismuth subsalicylate, and iron-containing products. A separation of at least 2 to 3 hours between administration of these agents and tetracycline antibiotics has been recommended.
In clinical trials with sarecycline in patients with acne vulgaris, the only adverse reaction reported in at least 1% of patients was nausea (3%, sarecycline vs. 2%, placebo). Diarrhea, and enterocolitis are also possible adverse GI reactions related to systemic antibiotic use.
Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with sarecycline. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Vulvovaginal mycotic infection (0.8%) and vulvovaginal candidiasis (0.6%) in patients during clinical trials.
Photosensitivity can appear within minutes of taking tetracycline antibiotics if the patient is exposed to direct sunlight or UV light. Photosensitivity is manifested by an exaggerated sunburn reaction and sarecycline should be discontinued at the first evidence of skin erythema. Red rash and onycholysis have been reported on those areas exposed to sunlight. Paresthesias (tingling and burning) in the hands, feet, and nose may indicate latent photosensitivity. If the drug is discontinued, symptoms usually are alleviated within 1 to 2 days. Sunscreens seem to provide only limited protection, and severe response may necessitate treatment with corticosteroids or antihistamines. Photosensitivity is a toxic, rather than an allergic, reaction.
Tooth discoloration has been seen in children who received a tetracycline antibiotic, but this reaction has also been reported in adults. This reaction is more common during long-term use of these drugs, although it has also been observed with repeated short-term courses. Enamel hypoplasia can result.
Benign increased intracranial pressure (pseudotumor cerebri) has been associated with the use of tetracyclines in adults and adolescents. Clinical manifestations include headache, blurred vision, diplopia, visual impairment or vision loss, and papilledema. Symptoms are usually reversible after discontinuation of the drug; however, permanent vision loss can occur.
Central nervous system adverse reactions, including dizziness, lightheadedness, and vertigo, have been reported with tetracycline use and tend to disappear rapidly once the drug is discontinued.
Animal data indicate that sarecycline may cause spermatogenesis inhibition and subsequent infertility in males.
Sarecycline is contraindicated in patients with known tetracyclines hypersensitivity.
Tetracyclines, like sarecycline, may have a serious effect on the bones and teeth in young children; use of tetracyclines in neonates, infants, and children younger than 8 years is not recommended. Tetracyclines are incorporated into bones and teeth that are undergoing calcification. This may cause permanent yellow or brown discoloration and enamel hypoplasia in developing teeth.
Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including sarecycline, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
Photosensitivity is a risk of tetracycline therapy and may occur with sarecycline. Clinically, the effect appears like an exaggerated sunburn reaction. Advise patients to avoid or minimize direct sunlight (UV) exposure. Photosensitivity reactions are believed to be caused by an accumulation of the drug in the skin and are mostly phototoxic, but photoallergic reactions can also occur. Reactions can develop within a few minutes or up to several hours after exposure and can occur 1 to 2 days after discontinuation of the drug. Advise drug recipients to avoid excess sunlight/artificial ultraviolet light whenever possible, use sunscreens, and to discontinue sarecycline therapy if phototoxicity occurs (i.e., skin eruption).
Tetracyclines have been associated with increased intracranial pressure in adults and adolescents. Women of childbearing age with obesity or a prior history of intracranial hypertension are at higher risk for developing intracranial hypertension. Since blurred vision, diplopia, and permanent vision loss are potential clinical manifestations of intracranial hypertension, ophthalmologic evaluations (i.e., fundoscopy) are advised for patients developing visual symptoms while receiving sarecycline. If visual disturbance occurs during treatment, evaluate patients for papilledema. Stopping the drug usually resolves intracranial hypertension; however, pressures may remain elevated for weeks after treatment discontinuation. Continue to monitor patients until they stabilize. In addition, avoid concurrent use of sarecycline with isotretinoin, as isotretinoin is also associated with increased intracranial pressures.
Sarecycline can cause dizziness, light-headedness, and vertigo; therefore, patients should know how they react to the drug before driving or operating machinery or engaging in activities requiring coordination and concentration. These symptoms may disappear during therapy or after the drug is discontinued.
Sarecycline, like all tetracycline class drugs, may cross the placenta and cause fetal harm, permanent discoloration of teeth, and reversible inhibition of bone growth when given during pregnancy. The potential risk to the fetus outweighs the potential benefit to the mother from sarecycline use during pregnancy; therefore, discontinue sarecycline as soon as pregnancy is recognized. Adequate and well-controlled studies of sarecycline use in pregnant women are lacking. In animal reproduction studies, sarecycline induced skeletal malformations in fetuses occurred when orally administered to pregnant rats during the period of organogenesis at a dose 1.4-times the maximum recommended human dose (MRHD) of 150 mg/day (based on AUC comparison). When dosing with sarecycline continued through the period of lactation, decreases in offspring survival, offspring body weight, and implantation sites and viable embryos in offspring females occurred at a dose 3-times the MRHD (based on AUC comparison).
Tetracyclines are excreted in human milk. Due to the potential for serious adverse reactions on bone and tooth development in nursing infants from tetracycline-class antibiotics, breast-feeding is not recommended during sarecycline therapy. However, because tetracyclines bind to calcium in maternal breast milk, the risk for oral absorption by the infant may be minimal.
Sarecycline is associated with reproductive risk. Sarecycline may cause infertility in male patients; therefore, avoid sarecycline in males attempting to conceive. In animal studies, sarecycline adversely affected spermatogenesis when orally administered at a dose 8-times the maximum recommended human dose (based on AUC comparison). Decreased sperm motility, decreased sperm count and concentration, and an increase in the percent of abnormal sperm were noted.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Propionibacterium acnes
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
For the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris:
Oral dosage:
Adults weighing 85 to 136 kg: 150 mg PO once daily. If there is no improvement after 12 weeks, reassess treatment. Efficacy of sarecycline beyond 12 weeks and safety beyond 12 months have not been established.
Adults weighing 55 to 84 kg: 100 mg PO once daily. If there is no improvement after 12 weeks, reassess treatment. Efficacy of sarecycline beyond 12 weeks and safety beyond 12 months have not been established.
Adults weighing less than 55 kg: 60 mg PO once daily. If there is no improvement after 12 weeks, reassess treatment. Efficacy of sarecycline beyond 12 weeks and safety beyond 12 months have not been established.
Children and Adolescents 9 to 17 years weighing 85 kg or more: 150 mg PO once daily. If there is no improvement after 12 weeks, reassess treatment. Efficacy of sarecycline beyond 12 weeks and safety beyond 12 months have not been established.
Children and Adolescents 9 to 17 years weighing 55 to 84 kg: 100 mg PO once daily. If there is no improvement after 12 weeks, reassess treatment. Efficacy of sarecycline beyond 12 weeks and safety beyond 12 months have not been established.
Children and Adolescents 9 to 17 years weighing 33 to 54 kg: 60 mg PO once daily. If there is no improvement after 12 weeks, reassess treatment. Efficacy of sarecycline beyond 12 weeks and safety beyond 12 months have not been established.
Maximum Dosage Limits:
-Adults
weight 85 to 136 kg: 150 mg/day PO.
weight 55 to 84 kg: 100 mg/day PO.
weight less than 55 kg: 60 mg/day PO.
-Geriatric
weight 85 to 136 kg: 150 mg/day PO.
weight 55 to 84 kg: 100 mg/day PO.
weight less than 55 kg: 60 mg/day PO.
-Adolescents
weight 85 kg or more: 150 mg/day PO.
weight 55 to 84 kg: 100 mg/day PO.
weight 33 to 54 kg: 60 mg/day PO.
-Children
9 to 12 years weighing 85 kg or more: 150 mg/day PO.
9 to 12 years weighing 55 to 84 kg: 100 mg/day PO.
9 to 12 years weighing 33 to 54 kg: 60 mg/day PO.
1 to 8 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Acitretin: (Contraindicated) The concomitant use of acitretin and systemic tetracyclines is contraindicated, due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retinoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
Afatinib: (Moderate) If the concomitant use of sarecycline and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of sarecycline. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-glycoprotein (P-gp) substrate; sarecycline is a P-gp inhibitor. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib.
Aluminum Hydroxide: (Major) Separate administration of sarecycline and antacids by 2 to 3 hours. Coadministration may impair absorption of sarecycline which may decrease its efficacy.
Aluminum Hydroxide; Magnesium Carbonate: (Major) Separate administration of sarecycline and antacids by 2 to 3 hours. Coadministration may impair absorption of sarecycline which may decrease its efficacy.
Aluminum Hydroxide; Magnesium Hydroxide: (Major) Separate administration of sarecycline and antacids by 2 to 3 hours. Coadministration may impair absorption of sarecycline which may decrease its efficacy.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Major) Separate administration of sarecycline and antacids by 2 to 3 hours. Coadministration may impair absorption of sarecycline which may decrease its efficacy.
Aluminum Hydroxide; Magnesium Trisilicate: (Major) Separate administration of sarecycline and antacids by 2 to 3 hours. Coadministration may impair absorption of sarecycline which may decrease its efficacy.
Aminolevulinic Acid: (Moderate) Tetracyclines cause photosensitivity and may increase the photosensitizing effects photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation and the use of protective clothing and sunscreens on exposed skin.
Amoxicillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Amoxicillin; Clarithromycin; Omeprazole: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Amoxicillin; Clavulanic Acid: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Ampicillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Ampicillin; Sulbactam: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Antacids: (Major) Separate administration of sarecycline and antacids by 2 to 3 hours. Coadministration may impair absorption of sarecycline which may decrease its efficacy.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Major) Early reports noted an increase in the excretion of tetracyclines during coadministration with sodium bicarbonate, and that the oral absorption of tetracyclines is reduced by sodium bicarbonate via increased gastric pH. However, conflicting data have been reported, and further study is needed. Two recent studies show no effect of oral sodium bicarbonate administration on tetracycline oral bioavailability. In one of these trials, coadministration with sodium bicarbonate was reported to have no effect on tetracycline urinary excretion, Cmax, or AUC. Until more information is available, avoid simultaneous administration of sodium bicarbonate and tetracyclines. When concurrent therapy is needed, stagger administration times by several hours to minimize the potential for interaction, and monitor for antimicrobial efficacy.
Atracurium: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Betrixaban: (Major) Avoid betrixaban use in patients with severe renal impairment receiving sarecycline. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving sarecycline. Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; sarecycline inhibits P-gp.
Bexarotene: (Major) The concomitant use of systemic retinoid therapy, such as bexarotene, and systemic tetracyclines should be avoided due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with systemic retionoid use alone and early signs and symptoms include papilledema, headache, nausea, vomiting and visual disturbances.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
Bismuth Subsalicylate: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Separate administration of oral tetracyclines and bismuth subsalicylate by at least 2 to 3 hours. Coadministration may impair absorption of oral tetracyclines which may decrease their efficacy. Some data suggest that this interaction may only apply to administration with bismuth subsalicylate suspension.
Calcium Acetate: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Calcium Carbonate: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Calcium Carbonate; Magnesium Hydroxide: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Calcium Carbonate; Magnesium Hydroxide; Simethicone: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Calcium Carbonate; Simethicone: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Calcium Chloride: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Calcium Gluconate: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Calcium: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Calcium; Vitamin D: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Chlorpheniramine; Pseudoephedrine: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.
Cholestyramine: (Major) Colestipol has been shown to reduce tetracycline absorption by roughly 50%. It is likely this is enough to cause a clinically significant effect. Although no data are available for other tetracyclines, or for cholestyramine, it should be assumed that any tetracycline antibiotic may be affected similarly by either cholestyramine or colestipol. Staggering oral doses of each agent is recommended to minimize this pharmacokinetic interaction. To minimize drug interactions, administer tetracyclines at least 1 hour before or at least 4 to 6 hours after the administration of cholestyramine. Since doxycycline undergoes enterohepatic recirculation, it may be even more susceptible to this drug interaction than the other tetracyclines.
Chromium: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Colchicine: (Major) Avoid concomitant use of colchicine and sarecycline due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and sarecycline is a P-gp inhibitor.
Colesevelam: (Moderate) Colesevelam may decrease the bioavailability of tetracyclines. To minimize potential for interactions, consider administering oral tetracyclines at least 4 hours before colesevelam. The manufacturer for colesevelam suggests monitoring serum drug concentrations and/or clinical effects for those drugs for which alterations in serum blood concentrations have a clinically significant effect on safety or efficacy.
Colestipol: (Major) Colestipol has been shown to reduce tetracycline absorption by roughly 50%. It is likely this is enough to cause a clinically significant effect. Although no data are available for other tetracyclines, it should be assumed that any tetracycline antibiotic may be affected similarly by colestipol. Staggering oral doses of each agent is recommended to minimize this pharmacokinetic interaction; administer tetracyclines at least 1 hour before or at least 4 to 6 hours after the administration of colestipol. Since doxycycline undergoes enterohepatic recirculation, it may be even more susceptible to this drug interaction than the other tetracyclines.
Dicloxacillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Didanosine, ddI: (Major) Tetracyclines should not be administered simultaneously with didanosine, ddI chewable tablets or powder for oral solution. The buffering agents contained in didanosine tablets and powder reduce tetracycline absorption. Administer oral doses of tetracycline antibiotics 1 hour before or 4 hours after didanosine tablet or powder administration. The delayed-release didanosine capsules do not contain a buffering agent and would not be expected to interact with tetracycline antibiotics.
Dienogest; Estradiol valerate: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Digoxin: (Major) Measure serum digoxin concentrations before initiating sarecycline. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 30% to 50% or by modifying the dosing frequency and continue monitoring. Coadministration may increase serum concentrations of digoxin. Digoxin is a substrate for P-glycoprotein (P-gp); sarecycline is an inhibitor of P-gp. Coadministration of a single dose of sarecycline 150 mg resulted in a 26% increase in the Cmax of digoxin.
Doxorubicin Liposomal: (Major) Avoid coadministration of sarecycline with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Doxorubicin is a substrate of P-glycoprotein (P-gp); sarecycline is a P-gp inhibitor. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effects of doxorubicin.
Doxorubicin: (Major) Avoid coadministration of sarecycline with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Doxorubicin is a substrate of P-glycoprotein (P-gp); sarecycline is a P-gp inhibitor. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of P-gp, resulting in increased concentration and clinical effects of doxorubicin.
Estradiol: (Moderate) It was previously thought that antibiotics may decrease the effectiveness of oral contraceptives containing estrogens due to stimulation of estrogen metabolism or a reduction in estrogen enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with oral contraceptives (OCs) and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma levels of oral contraceptives. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review of the subject concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with sarecycline is necessary. The dose of everolimus may need to be reduced. Everolimus is a P-glycoprotein (P-gp) substrate and sarecycline is a P-gp inhibitor. Coadministration with P-gp inhibitors may decrease the efflux of everolimus from intestinal cells and increase everolimus blood concentrations.
Ferric Maltol: (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
Halobetasol; Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as tetracyclines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Heparin: (Minor) Tetracyclines may partially counteract the anticoagulant actions of heparin, according to the product labels. However, this interaction is not likely of clinical significance in most patients since heparin therapy is adjusted to the partial thromboplastin time (aPTT) and other clinical parameters of the patient.
Insoluble Prussian Blue: (Moderate) The binding of Insoluble Prussian Blue to some orally administered therapeutic drugs and essential nutrients is possible. The blood concentrations and/or clinical response to critical coadministered products should be monitored during Insoluble Prussian Blue therapy.
Iron Salts: (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
Iron Sucrose, Sucroferric Oxyhydroxide: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of tetracyclines will be significantly reduced by orally administered compounds that contain iron salts. To minimize the potential for this interaction, administer tetracycline antibiotics at least 1 hour before oral iron sucrose, sucroferric oxyhydroxide.
Iron: (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
Isotretinoin: (Major) Avoid the concomitant use of isotretinoin and systemic tetracyclines due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with both systemic retinoid and tetracycline use alone. Early signs and symptoms include papilledema, headache, nausea, vomiting, and visual disturbances.
Lansoprazole; Amoxicillin; Clarithromycin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Lanthanum Carbonate: (Major) Oral compounds known to interact with antacids, like tetracyclines, should not be taken within 2 hours of dosing with lanthanum carbonate. If these agents are used concomitantly, space the dosing intervals appropriately. Monitor serum concentrations and clinical condition.
Lapatinib: (Moderate) Monitor for an increase in lapatinib-related adverse reactions if coadministration with sarecycline is necessary. Lapatinib is a P-glycoprotein (P-gp) substrate and sarecycline is a P-gp inhibitor. Increased plasma concentrations of lapatinib are likely.
Lefamulin: (Moderate) Monitor for lefamulin-related adverse effects if oral lefamulin is administered with sarecycline as concurrent use may increase exposure from lefamulin tablets; an interaction is not expected with intravenous lefamulin. Lefamulin is a CYP3A4 and P-gp substrate and sarecycline is a P-gp inhibitor.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
Lomitapide: (Moderate) Caution should be exercised when lomitapide is used with other medications known to have potential for hepatotoxicity, such as tetracyclines. The effect of concomitant administration of lomitapide with other hepatotoxic medications is unknown. More frequent monitoring of liver-related tests may be warranted.
Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with sarecycline. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and sarecycline is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with sarecycline. Concurrent use may increase loperamide exposure. Loperamide is a P-gp substrate and sarecycline is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased loperamide plasma concentrations by 2- to 3-fold.
Magnesium Citrate: (Moderate) Administer magnesium citrate at least 3 hours before or 3 hours after orally administered tetracyclines. Tetracycline absorption may be reduced as tetracycline antibiotics can chelate with divalent or trivalent cations.
Magnesium Hydroxide: (Major) Separate administration of sarecycline and antacids by 2 to 3 hours. Coadministration may impair absorption of sarecycline which may decrease its efficacy.
Magnesium Salts: (Major) Separate administration of sarecycline and antacids by 2 to 3 hours. Coadministration may impair absorption of sarecycline which may decrease its efficacy. (Moderate) Administer oral magnesium-containing products at least 3 hours before or 3 hours after orally administered tetracyclines. Tetracycline absorption may be reduced as tetracycline antibiotics can chelate with divalent or trivalent cations.
Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: (Major) Administer tetracyclines at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of tetracyclines may be reduced by chelation with magnesium sulfate.
Magnesium: (Moderate) Administer oral magnesium-containing products at least 3 hours before or 3 hours after orally administered tetracyclines. Tetracycline absorption may be reduced as tetracycline antibiotics can chelate with divalent or trivalent cations.
Methotrexate: (Moderate) Monitor for methotrexate-related adverse reactions during concomitant tetracyclines use. Tetracyclines may decrease intestinal absorption of methotrexate or interfere with the enterohepatic circulation by inhibiting bowel flora and suppressing metabolism of methotrexate by bacteria.
Methoxsalen: (Moderate) Use methoxsalen and tetracyclines together with caution; the risk of severe burns/photosensitivity may be additive. If concurrent use is necessary, closely monitor patients for signs or symptoms of skin toxicity.
Molindone: (Major) The tablet formulation of molindone contains calcium sulfate as an excipient and the calcium ions may interfere with the absorption of tetracyclines. It may be advisable to consider an alternative to tetracycline treatment during molindone administration.
Nafcillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Nanoparticle Albumin-Bound Sirolimus: (Major) Avoid concomitant use of sirolimus and sarecycline. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and sarecycline is a P-gp inhibitor.
Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
Omeprazole; Amoxicillin; Rifabutin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Omeprazole; Sodium Bicarbonate: (Major) Early reports noted an increase in the excretion of tetracyclines during coadministration with sodium bicarbonate, and that the oral absorption of tetracyclines is reduced by sodium bicarbonate via increased gastric pH. However, conflicting data have been reported, and further study is needed. Two recent studies show no effect of oral sodium bicarbonate administration on tetracycline oral bioavailability. In one of these trials, coadministration with sodium bicarbonate was reported to have no effect on tetracycline urinary excretion, Cmax, or AUC. Until more information is available, avoid simultaneous administration of sodium bicarbonate and tetracyclines. When concurrent therapy is needed, stagger administration times by several hours to minimize the potential for interaction, and monitor for antimicrobial efficacy.
Oxacillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Palovarotene: (Major) Avoid concomitant use of palovarotene and tetracyclines due to an increased risk for intracranial hypertension. Both tetracyclines and retinoids have been associated with this adverse effect and concomitant use may increase risk.
Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Penicillin G Benzathine: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Penicillin G Benzathine; Penicillin G Procaine: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Penicillin G Procaine: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Penicillin G: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Penicillin V: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Penicillins: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Photosensitizing agents (topical): (Moderate) Tetracyclines cause photosensitivity and may increase the photosensitizing effects photosensitizing agents used in photodynamic therapy. Prevention of photosensitivity includes adequate protection from sources of UV radiation and the use of protective clothing and sunscreens on exposed skin.
Piperacillin; Tazobactam: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Polycarbophil: (Major) Coadministration of calcium polycarbophil with orally administered tetracyclines can decrease the absorption of tetracyclines; oral doses of tetracyclines should be given 2 hours before or after the administration of calcium polycarbophil. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg). This effect is presumably due to the chelation of the antibiotic by the calcium.
Polyethylene Glycol; Electrolytes: (Major) Administer tetracyclines at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of tetracyclines may be reduced by chelation with magnesium sulfate.
Polyethylene Glycol; Electrolytes; Ascorbic Acid: (Major) Administer tetracyclines at least 2 hours before or 6 hours after administration of magnesium sulfate; potassium sulfate; sodium sulfate. The absorption of tetracyclines may be reduced by chelation with magnesium sulfate.
Polysaccharide-Iron Complex: (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
Porfimer: (Major) Avoid coadministration of porfimer with tetracyclines due to the risk of increased photosensitivity. Porfimer is a light-activated drug used in photodynamic therapy; all patients treated with porfimer will be photosensitive. Concomitant use of other photosensitizing agents like tetracyclines may increase the risk of a photosensitivity reaction.
Pralsetinib: (Major) Avoid concomitant use of sarecycline with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a P-gp substrate and sarecycline is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased the overall exposure of pralsetinib by 81%.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and sarecycline due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a P-gp substrate and sarecycline is a P-gp inhibitor.
Pyridostigmine: (Moderate) Parenteral administration of high doses of certain antibiotics such as tetracyclines may intensify or produce neuromuscular block through their own pharmacologic actions. If unexpected prolongation of neuromuscular block or resistance to its reversal with pyridostigmine occurs, consider the possibility of an antibiotic effect.
Pyridoxine, Vitamin B6: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Quinapril: (Major) Tetracycline absorption is reduced by about 28 to 37% with coadministration with quinapril, presumably due to the magnesium in the quinapril tablet. This interaction should be taken into account when prescribing tetracyclines with quinapril.
Quinapril; Hydrochlorothiazide, HCTZ: (Major) Tetracycline absorption is reduced by about 28 to 37% with coadministration with quinapril, presumably due to the magnesium in the quinapril tablet. This interaction should be taken into account when prescribing tetracyclines with quinapril.
Relugolix: (Major) Avoid concomitant use of relugolix and oral sarecycline. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer sarecycline at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and sarecycline is a P-gp inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of relugolix and oral sarecycline. Concomitant use may increase relugolix exposure and the risk of relugolix-related adverse effects. If concomitant use is unavoidable, administer sarecycline at least 6 hours after relugolix and monitor for adverse reactions. Relugolix is a P-glycoprotein (P-gp) substrate and sarecycline is a P-gp inhibitor.
Repotrectinib: (Major) Avoid coadministration of repotrectinib with sarecycline due to increased repotrectinib exposure which may increase the risk for repotrectinib-related adverse effects. Repotrectinib is a P-gp substrate and sarecycline is a P-gp inhibitor.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with sarecycline is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and sarecycline is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with sarecycline; concurrent use may increase rimegepant exposure. Rimegepant is a P-gp substrate and sarecycline is a P-gp inhibitor.
Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of sarecycline. Coadministration may increase sirolimus concentrations and the risk for sirolimus-related adverse effects. Sirolimus is a P-gp substrate and sarecycline is a P-gp inhibitor.
Sodium Bicarbonate: (Major) Early reports noted an increase in the excretion of tetracyclines during coadministration with sodium bicarbonate, and that the oral absorption of tetracyclines is reduced by sodium bicarbonate via increased gastric pH. However, conflicting data have been reported, and further study is needed. Two recent studies show no effect of oral sodium bicarbonate administration on tetracycline oral bioavailability. In one of these trials, coadministration with sodium bicarbonate was reported to have no effect on tetracycline urinary excretion, Cmax, or AUC. Until more information is available, avoid simultaneous administration of sodium bicarbonate and tetracyclines. When concurrent therapy is needed, stagger administration times by several hours to minimize the potential for interaction, and monitor for antimicrobial efficacy.
Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Separate administration of tetracyclines and iron by 2 to 3 hours. Iron may decrease the oral bioavailability of tetracyclines.
Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Moderate) Administer oral magnesium-containing products at least 3 hours before or 3 hours after orally administered tetracyclines. Tetracycline absorption may be reduced as tetracycline antibiotics can chelate with divalent or trivalent cations.
Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Sucralfate: (Moderate) Sucralfate should be given 2 hours before or after the oral administration of tetracyclines. Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain aluminum salts, calcium salts, iron salts, magnesium salts, and/or zinc salts. Sucralfate, because it contains aluminum in its structure and due to its mechanism of action, can bind with tetracyclines in the GI tract, reducing the bioavailability of these agents.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if coadministration with sarecycline is necessary. Talazoparib is a P-gp substrate and sarecycline is a P-gp inhibitor.
Tazarotene: (Moderate) The manufacturer states that tazarotene should be administered with caution in patients who are also taking drugs known to be photosensitizers, such as tetracyclines, as concomitant use may augment phototoxicity. Patients should take care and use proper techniques to limit sunlight and UV exposure of treated areas.
Topotecan: (Major) Avoid coadministration of sarecycline with oral topotecan due to increased topotecan exposure; sarecycline may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp); sarecycline is a P-gp inhibitor.
Tretinoin, ATRA: (Major) Avoid the concomitant use of tretinoin and systemic tetracyclines due to the potential for increased cranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Pseudotumor cerebri has been reported with both systemic retinoid and tetracycline use alone. Early signs and symptoms include papilledema, headache, nausea, vomiting, and visual disturbances.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with sarecycline. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a substrate of the P-gp drug transporter; sarecycline is a P-gp inhibitor.
Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and tetracyclines may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with sarecycline due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of sarecycline. Venetoclax is a P-glycoprotein (P-gp) substrate; sarecycline is a P-gp inhibitor. Coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with tetracyclines is necessary due to the risk of increased photosensitivity. Verteporfin is a light-activated drug used in photodynamic therapy; all patients treated with verteporfin will be photosensitive. Concomitant use of other photosensitizing agents like tetracyclines may increase the risk of a photosensitivity reaction.
Vitamin D: (Moderate) Divalent or trivalent cations readily chelate with tetracycline antibiotics, forming insoluble compounds. The oral absorption of these antibiotics will be significantly reduced by other orally administered compounds that contain calcium salts, particularly if the time of administration is within 60 minutes of each other. Calcium salts and tetracyclines should not be administered within 1 to 2 hours of each other, although doxycycline chelates less with calcium than other tetracyclines.
Vonoprazan; Amoxicillin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Vonoprazan; Amoxicillin; Clarithromycin: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Warfarin: (Moderate) Tetracyclines may increase the action of warfarin and other oral anticoagulants by either impairing prothrombin utilization or, possibly, decreasing production of vitamin K because of its antiinfective action on gut bacteria. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.
Zinc Salts: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.
Zinc: (Major) Concurrent administration of oral zinc salts with oral tetracyclines can decrease the absorption of these antiinfectives and possibly interfere with their therapeutic response. This is a result of the formation of insoluble chelates between zinc and the antiinfective. Oral zinc supplements should be administered at least 6 hours before or 2 hours after administering tetracyclines.
Sarecycline is an aminomethylcycline within the tetracycline class. It's mechanism of action in treating inflammatory lesions of non-nodular acne vulgaris is unknown. In C. acnes, sarecycline binds to the 30S ribosomal subunit and interacts with the 16S ribosomal RNA. It protrudes its C7 moiety into the mRNA binding channel to interact with mRNA. Sarecycline blocks C. acnes protein synthesis and inhibits bacteria growth.
Sarecycline is administered orally. Protein binding is approximately 63% to 75% in vitro. The mean apparent volume of distribution of sarecycline at steady state ranges from 91 to 97 L. Metabolism of sarecycline by enzymes in human liver microsomes is minimal (less than 15%) in vitro. Minor metabolites resulting from non-enzymic epimerization, O-/N-demethylation, hydroxylation, and desaturation have been found. After a single 100 mg dose of radiolabeled sarecycline, approximately 43% of the dose was recovered in the feces (15% as unchanged drug) and 44% in the urine (25% as unchanged drug). The mean apparent oral clearance and elimination half-life of sarecycline at steady state are 3 L/hour and 21 to 22 hours, respectively.
Affected cytochrome P450 isoenzymes and drug transporters: P-glycoprotein (P-gp)
Sarecycline is a P-gp inhibitor.
-Route-Specific Pharmacokinetics
Oral Route
Peak sarecycline plasma concentrations are reached at a median of 1.5 to 2 hours after administration. Coadministration with a high-fat, high-calorie meal (that included milk) delayed peak concentrations by approximately 0.5 hours and decreased sarecycline Cmax and AUC by 31% and 27%, respectively. Increasing the sarecycline dose from 60 to 150 mg once daily in healthy subjects resulted in a slightly less than proportional increase in steady-state Cmax and AUC. The mean accumulation ratio of sarecycline ranges from 1.5- to 1.6-fold with repeated dosing. Steady-state of sarecycline is reached by Day 7.
-Special Populations
Hepatic Impairment
No clinically significant differences in the pharmacokinetics of sarecycline were observed in patients with mild to moderate hepatic impairment (Child-Pugh A or B). The pharmacokinetics of sarecycline have not been evaluated in patients with severe hepatic impairment (Child-Pugh C).
Renal Impairment
No clinically significant differences in the pharmacokinetics of sarecycline were observed in patients with renal impairment. The pharmacokinetics of sarecycline have not been evaluated in patients with end-stage renal disease (ESRD).
Pediatrics
No clinically significant differences in the pharmacokinetics of sarecycline were observed in pediatric patients (11 years and older).
Geriatric
No clinically significant differences in the pharmacokinetics of sarecycline were observed in geriatric patients (up to 73 years).
Gender Differences
No clinically significant differences in the pharmacokinetics of sarecycline were observed based on gender.
Obesity
No clinically significant differences in the pharmacokinetics of sarecycline were observed based on weight (42 to 133 kg).