Seysara

Drug overview for SEYSARA (sarecycline hcl):

Generic name: sarecycline HCl (SAR-e-SYE-kleen)
Drug class: Tetracyclines
Therapeutic class: Anti-Infective Agents

Sarecycline hydrochloride is a tetracycline anti-infective agent.

No enhanced Uses information available for this drug.

DRUG IMAGES

SEYSARA 60 MG TABLET
SEYSARA 100 MG TABLET
SEYSARA 150 MG TABLET

The following indications for SEYSARA (sarecycline hcl) have been approved by the FDA:

Indications:
Acne vulgaris

Professional Synonyms:
Acne simplex
Common acne
Simple acne

Dosing information for SEYSARA
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
SEYSARA 60 MG TABLET	Maintenance	Adults take 1 tablet (60 mg) by oral route once daily
SEYSARA 100 MG TABLET	Maintenance	Adults take 1 tablet (100 mg) by oral route once daily
SEYSARA 150 MG TABLET	Maintenance	Adults take 1 tablet (150 mg) by oral route once daily

The following drug interaction information is available for SEYSARA (sarecycline hcl):

Contraindicated
Severe
Moderate

There are 1 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
Selected Retinoids (Systemic)/Tetracyclines SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Both systemic tetracyclines(1-4,14) and systemic retinoids(5-14) have been independently associated with medication-induced intracranial hypertension. CLINICAL EFFECTS: The concurrent use of oral retinoids(5-12) with tetracyclines has been associated with pseudotumor cerebri (benign intracranial hypertension). Early signs of pseudotumor cerebri include papilledema (inflammation of the optic nerve), headache, nausea, vomiting, and visual disturbances such as blurred vision, double vision, and loss of vision.(15) PREDISPOSING FACTORS: Women of childbearing age who are overweight or have a previous history of intracranial hypertension are at a greater risk of developing intracranial hypertension.(15) PATIENT MANAGEMENT: The UK(5) and US(6) manufacturers of acitretin state state that concurrent use with tetracyclines is contraindicated. The UK manufacturer of isotretinoin states that concurrent use with tetracyclines is contraindicated.(7) The US manufacturer of isotretinoin states that the concurrent use of tetracyclines should be avoided.(8) The US manufacturer of minocycline states that the administration of isotretinoin should be avoided shortly before, during and shortly after minocycline therapy.(2) The UK manufacturers of oral tretinoin and alitretinoin states that concurrent use with tetracyclines is contraindicated.(9,11) The Canadian manufacturer of palovarotene states that coadministration of tetracycline derivatives should be avoided.(12) Patients who present with symptoms of pseudotumor cerebri should be screened for papilledema. If papilledema is present, they should discontinue the drug and be referred to a neurologist for further treatment.(5-13) DISCUSSION: The concurrent use of isotretinoin and tetracyclines has been associated with pseudotumor cerebri.(5-13) A review of ocular side effects from the National Registry of Drug-Induced Ocular Side Effects, the World Health Organization, the Food and Drug Administration, and medical journals from 1979 to 2003 found 6 patients who developed intracranial hypertension while taking concurrent minocycline or tetracycline with tretinoin, acitretin, or etretinate.(13)	ABSORICA, ABSORICA LD, ACCUTANE, ACITRETIN, AMNESTEEM, CLARAVIS, ISOTRETINOIN, RETINOIC ACID, SOHONOS, TRETINOIN, TRETINOIN ACID, ZENATANE

Drug Interaction

Drug Names

Selected Retinoids (Systemic)/Tetracyclines

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Both systemic tetracyclines(1-4,14) and systemic retinoids(5-14) have been independently associated with medication-induced intracranial hypertension.

CLINICAL EFFECTS: The concurrent use of oral retinoids(5-12) with tetracyclines has been associated with pseudotumor cerebri (benign intracranial hypertension). Early signs of pseudotumor cerebri include papilledema (inflammation of the optic nerve), headache, nausea, vomiting, and visual disturbances such as blurred vision, double vision, and loss of vision.(15)

PREDISPOSING FACTORS: Women of childbearing age who are overweight or have a previous history of intracranial hypertension are at a greater risk of developing intracranial hypertension.(15)

PATIENT MANAGEMENT: The UK(5) and US(6) manufacturers of acitretin state state that concurrent use with tetracyclines is contraindicated. The UK manufacturer of isotretinoin states that concurrent use with tetracyclines is contraindicated.(7) The US manufacturer of isotretinoin states that the concurrent use of tetracyclines should be avoided.(8)

The US manufacturer of minocycline states that the administration of isotretinoin should be avoided shortly before, during and shortly after minocycline therapy.(2) The UK manufacturers of oral tretinoin and alitretinoin states that concurrent use with tetracyclines is contraindicated.(9,11) The Canadian manufacturer of palovarotene states that coadministration of tetracycline derivatives should be avoided.(12)

Patients who present with symptoms of pseudotumor cerebri should be screened for papilledema. If papilledema is present, they should discontinue the drug and be referred to a neurologist for further treatment.(5-13)

DISCUSSION: The concurrent use of isotretinoin and tetracyclines has been associated with pseudotumor cerebri.(5-13) A review of ocular side effects from the National Registry of Drug-Induced Ocular Side Effects, the World Health Organization, the Food and Drug Administration, and medical journals from 1979 to 2003 found 6 patients who developed intracranial hypertension while taking concurrent minocycline or tetracycline with tretinoin, acitretin, or etretinate.(13)

ABSORICA, ABSORICA LD, ACCUTANE, ACITRETIN, AMNESTEEM, CLARAVIS, ISOTRETINOIN, RETINOIC ACID, SOHONOS, TRETINOIN, TRETINOIN ACID, ZENATANE

There are 8 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Topical Tretinoin/Tetracyclines SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. CLINICAL EFFECTS: Concurrent use of topical tretinoin with tetracyclines may increase the risk of phototoxicity(1) in some patients.(2) PREDISPOSING FACTORS: Patients using topical tretinoin for the treatment of photodamage may be predisposed to photosensitivity.(2) PATIENT MANAGEMENT: Concurrent use of topical tretinoin and tetracycline is standard practice in the treatment of acne.(3) However, patients taking tetracyclines should not use topical tretinoin (e.g Renova) for the treatment of photodamage.(1,2) DISCUSSION: The concurrent use of topical tretinoin and tetracyclines may result in an increased risk of phototoxicity.(1,2)	KATARYA, KATARYAXN, KETARYA, KEVARYA, KUTARYAXM, KUTARYAXMPA, KUVARYA, KUVARYE, MECORIX, MECORIX HP, MECORIX PLUS, MEKAM, MEKAM HP, MELIDU, MELONDIS, MELONDIS PLUS, MOLEXI, MYTHIUS, REFISSA, RENOVA, RENOVA PUMP, TRETINOIN, TRI-LUMA, YAXATARXYN, YOKATAR
Cholera Vaccine Live/Selected Antibiotics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Antibiotics with activity against Vibrio cholerae may attenuate the immunization response to the live cholera vaccine.(1) CLINICAL EFFECTS: Concurrent or recent antibiotic use may make the cholera vaccine ineffective.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of live cholera vaccine states that it should not be administered to patients who have received antibiotics within 14 days prior to vaccination.(1) If antimalarial prophylaxis with chloroquine is required, administer the live cholera vaccine at least 10 days before beginning chloroquine.(1) Antibiotics linked to this monograph are: macrolides, quinolones, tetracyclines, ampicillin, cefprozil, chloramphenicol, furazolidone, sulfamethoxazole-trimethoprim, and sulfametrole-trimethoprim.(2,3) DISCUSSION: Antibiotics with activity against Vibrio cholerae may attenuate the immunization response to the live cholera vaccine, rendering the vaccine ineffective.	VAXCHORA ACTIVE COMPONENT, VAXCHORA VACCINE
Aminolevulinic Acid/Selected Photosensitizers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Aminolevulinic acid, anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides are all known photosensitizers.(1) CLINICAL EFFECTS: Concurrent use of aminolevulinic acid in patients taking anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides may increase the risk of phototoxicity.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer states that aminolevulinic acid should be avoided in patients receiving photosensitizers including anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides for 24 hours before and after administration of aminolevulinic acid.(1) DISCUSSION: Because of the risk of increased photosensitivity, the US manufacturer states that aminolevulinic acid should be avoided in patients receiving photosensitizers including anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides for 24 hours before and after administration of aminolevulinic acid.(1)	AMINOLEVULINIC ACID HCL, GLEOLAN
Porfimer/Selected Photosensitizers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Porfimer causes photosensitivity due to residual drug which is present in all parts of the skin. Anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides are other known photosensitizers.(1) CLINICAL EFFECTS: Concurrent use of porfimer in patients taking anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides may increase the risk of phototoxicity.(1) PREDISPOSING FACTORS: Patients with any hepatic impairment and patients with severe renal impairment have reduced drug elimination and may remain photosensitive for 90 days or longer.(1) PATIENT MANAGEMENT: The US manufacturer of porfimer states that concurrent use of porfimer with photosensitizers including anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides should be avoided.(1) Since the photosensitive effect of porfimer may persist for at least 30 days (and for 90 days in some patients), it would be prudent to avoid other photosensitizing agents for at least 30 days after administration of porfimer. DISCUSSION: All patients who have received porfimer become photosensitive. It is unknown what the risk of photosensitivity reactions is when porfimer is used concurrently with other photosensitizing agents. When porfimer was used in clinical trials, photosensitivity reactions occurred in about 20% of cancer patients and in 69% of high-grade dysplasia in Barretts esophagus patients. Most of the reactions were mild to moderate erythema, but they also included swelling, pruritus, burning sensation, feeling hot, or blisters. The majority of reactions occurred within 90 days of porfimer administration.(1)	PHOTOFRIN
Relugolix/P-glycoprotein (P-gp) Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Relugolix is a substrate of the intestinal P-glycoprotein (P-gp) efflux transporter. Inhibitors of P-gp may increase the absorption of relugolix.(1) CLINICAL EFFECTS: The concurrent administration of relugolix with an inhibitor of P-glycoprotein may result in elevated levels of relugolix and adverse effects, including hot flashes, skin flushing, musculoskeletal pain, hyperglycemia, acute renal injury, transaminitis, arrhythmias, and hemorrhage.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of relugolix states that the coadministration of relugolix with P-gp inhibitors should be avoided. If the P-gp inhibitor is to be used short-term, relugolix may be held for up to 2 weeks. If treatment with relugolix is interrupted for longer than 7 days, resume relugolix with a loading dose of 360 mg on the first day, followed by 120 mg once daily.(1) If coadministration with a P-gp inhibitor cannot be avoided, relugolix should be taken at least 6 hours before the P-gp inhibitor. Monitor the patient more frequently for adverse events.(1) DISCUSSION: Coadministration of relugolix with erythromycin (a P-gp and moderate CYP3A4 inhibitor) increased the area-under-curve (AUC) and maximum concentration (Cmax) of relugolix by 6.2-fold. Voriconazole (a strong CYP3A4 inhibitor) did not have a clinically significant effect on the pharmacokinetics of relugolix.(1) P-gp inhibitors linked to this monograph include: amiodarone, asunaprevir, azithromycin, belumosudil, capmatinib, carvedilol, cimetidine, clarithromycin, cobicistat, conivaptan, curcumin, cyclosporine, daclatasvir, danicopan, daridorexant, diltiazem, diosmin, dronedarone, eliglustat, erythromycin, flibanserin, fluvoxamine, fostamatinib, ginkgo, ginseng, glecaprevir/pibrentasvir, indinavir, itraconazole, ivacaftor, josamycin, ketoconazole, lapatinib, lonafarnib, mavorixafor, mibefradil, mifepristone, neratinib, osimertinib, paroxetine, pirtobrutinib, propafenone, quinidine, quinine, ranolazine, ritonavir, sarecycline, schisandra, selpercatinib, simeprevir, sotorasib, telaprevir, telithromycin, tepotinib, tezacaftor, tucatinib, valbenazine, velpatasvir, vemurafenib, verapamil, vimseltinib, and voclosporin.(2,3)	MYFEMBREE, ORGOVYX
Doxorubicin/P-glycoprotein (P-gp) Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: P-glycoprotein (P-gp) inhibition may increase doxorubicin cellular concentration, as well as decrease biliary or renal elimination.(1) CLINICAL EFFECTS: Increased cellular or systemic levels of doxorubicin may result in doxorubicin toxicity, including cardiomyopathy, myelosuppression, or hepatic impairment.(1) PREDISPOSING FACTORS: The interaction magnitude may be greater in patients with impaired renal or hepatic function. PATIENT MANAGEMENT: Avoid the concurrent use of P-gp inhibitors in patients undergoing therapy with doxorubicin.(1) Consider alternatives with no or minimal inhibition. If concurrent therapy is warranted, monitor the patient closely for signs and symptoms of doxorubicin toxicity. DISCUSSION: Doxorubicin is a substrate of P-gp.(1) Clinical studies have identified and evaluated the concurrent use of doxorubicin and P-gp inhibitors as a target to overcome P-gp mediated multidrug resistance.(2,3) P-gp inhibitors linked to this monograph include: amiodarone, asciminib, asunaprevir, azithromycin, belumosudil, capmatinib, cimetidine, cyclosporine, daclatasvir, danicopan, daridorexant, diltiazem, diosmin, dronedarone, eliglustat, erythromycin, flibanserin, fluvoxamine, fostamatinib, ginkgo, ginseng, glecaprevir/pibrentasvir, hydroquinidine, istradefylline, ivacaftor, lapatinib, ledipasvir, mavorixafor, neratinib, osimertinib, paroxetine, pirtobrutinib, propafenone, quercetin, quinidine, quinine, ranolazine, sarecycline, schisandra, selpercatinib, simeprevir, sofosbuvir/velpatasvir/voxilaprevir, sotorasib, tepotinib, tezacaftor, valbenazine, vemurafenib, verapamil, vimseltinib, and voclosporin.(4,5)	ADRIAMYCIN, CAELYX, DOXIL, DOXORUBICIN HCL, DOXORUBICIN HCL LIPOSOME
Methoxsalen/Selected Photosensitizers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Methoxsalen causes photosensitivity due to residual drug which is present in all parts of the skin from photopheresis. Anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides are other known photosensitizers.(1) CLINICAL EFFECTS: Concurrent use of methoxsalen in patients taking anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides may increase the risk of phototoxicity.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of methoxsalen states that concurrent use of methoxsalen with anthralin, coal tar and derivatives, fluoroquinolones, griseofulvin, organic staining dyes (such as methylene blue, rose bengal, or toluidine blue), phenothiazines, selected NSAIDs (such as diclofenac, ketoprofen, nabumetone, naproxen, piroxicam, and tiaprofenic acid), St. John's wort, sulfonamides, sulfonylureas, tetracyclines, and thiazides should be avoided.(1) DISCUSSION: All patients who have received methoxsalen become photosensitive. It is unknown what the risk of photosensitivity reactions is when methoxsalen is used concurrently with other photosensitizing agents.(1)	METHOXSALEN, UVADEX
Fecal Microbiota Spores/Antibiotics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1) CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1) DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores.	VOWST

There are 3 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Tetracyclines/Divalent & Trivalent Cations SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Di- and trivalent cations may form chelation complexes with tetracyclines, preventing their absorption.(1,2) CLINICAL EFFECTS: Simultaneous administration of di- or trivalent cations may result in decreased levels of and therapeutics effects from tetracyclines. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Administer tetracyclines at least two hours before or after the di- or trivalent cations. When used for the treatment of H. pylori infection, tetracyclines and bismuth should be given simultaneously. The US manufacturer of omadacycline states to fast for at least four hours, administer omadacycline, and then wait four hours before taking di- or trivalent cations.(21) DISCUSSION: Concurrent administration of aluminum hydroxide or divalent cations (such as calcium, magnesium, or zinc) has been shown to significantly decrease the gastrointestinal absorption of tetracycline.(3-5) Concurrent administration of tetracycline and magnesium-aluminum hydroxide gel has been shown to decrease the tetracycline area-under-curve (AUC) by 90%.(6) Magnesium-aluminum silicate has been shown to decrease the AUC of tetracycline by 27%.(7) Demeclocycline(8,9) methacycline,(10) chlortetracycline,(11) and oxytetracycline(10,12) have been shown to interact with aluminum hydroxide and/or dairy products. Doxycycline has been reported to interact with aluminum hydroxide gel.(13) Aluminum magnesium hydroxide has been shown to decrease doxycycline absorption by 84%.(14) Minocycline absorption has been shown to be impaired by aluminum, calcium, and magnesium.(15) Bismuth subsalicylate has been shown to decrease absorption of doxycycline and tetracycline by 37%(16) and 34%,(17) respectively. Since sucralfate is an aluminum salt of a sulfated disaccharide, it may also prevent absorption of tetracyclines. This complex has been used to provide site-specific delivery of tetracycline to gastric ulcers in the treatment of Helicobacter pylori gastric ulcer disease and may be useful in some indications.(18) Quinapril tablets contain a high percentage of magnesium and have been shown to decrease the absorption of tetracycline by 28-37%.(19) Lanthanum is expected to interact with tetracyclines as well.(20)	ACCRUFER, ALUMINUM HYDROXIDE, ATTAPULGITE, AUROVELA 24 FE, AUROVELA FE, AURYXIA, BALCOLTRA, BISMUTH CITRATE, BISMUTH SUBSALICYLATE, BLISOVI 24 FE, BLISOVI FE, CALCIUM ACETATE, CALCIUM CHLORIDE, CALCIUM GLUCONATE, CALCIUM GLUCONATE MONOHYDRATE, CARAFATE, CHARLOTTE 24 FE, CLENPIQ, FEIRZA, FERRIC CITRATE, FINZALA, FOSRENOL, GEMMILY, HAILEY 24 FE, HAILEY FE, JOYEAUX, JUNEL FE, JUNEL FE 24, KAITLIB FE, KAOLIN, LANTHANUM CARBONATE, LARIN 24 FE, LARIN FE, LAYOLIS FE, LEVONORG-ETH ESTRAD-FE BISGLYC, LO LOESTRIN FE, LOESTRIN FE, MAGNESIUM CHLORIDE, MAGNESIUM CITRATE, MAGNESIUM OXIDE, MAGNESIUM SULFATE, MERZEE, MIBELAS 24 FE, MICROGESTIN FE, MINZOYA, NORETHIN-ETH ESTRA-FERROUS FUM, NORETHINDRONE-E.ESTRADIOL-IRON, SOD SULF-POTASS SULF-MAG SULF, SUCRALFATE, SUFLAVE, SUPREP, SUTAB, TARINA 24 FE, TARINA FE, TARINA FE 1-20 EQ, TAYTULLA, TILIA FE, TRI-LEGEST FE, VELPHORO, WYMZYA FE, XARAH FE, XELRIA FE, ZINC CHLORIDE, ZINC OXIDE, ZINC SULFATE
Digoxin, Oral/Tetracyclines SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: In approximately 10% of patients receiving digoxin, a considerable amount of an administered dose of the drug is metabolized by GI bacteria to inactive digoxin reduction products (DRPs). Concomitant administration of tetracycline may alter the GI flora, enabling an increased amount of digoxin to be absorbed. CLINICAL EFFECTS: Increased serum digoxin levels with possible toxicity may occur. This effect may persist for several months after tetracycline is discontinued. Symptoms of digoxin toxicity can include anorexia, nausea, vomiting, headache, fatigue, malaise, drowsiness, generalized muscle weakness, disorientation, hallucinations, visual disturbances, and arrhythmias. PREDISPOSING FACTORS: Low body weight, advanced age, impaired renal function, hypokalemia, hypercalcemia, and/or hypomagnesemia may increase the risk of digoxin toxicity. PATIENT MANAGEMENT: Monitor serum digoxin levels and observe the patient for toxicity. The dosage of digoxin may need to be decreased by 30-50% or the frequency of administration may be reduced.(3) DISCUSSION: Approximately 10% of the patients receiving digoxin metabolize 30% or more of an ingested dose of digoxin to inactive DRPs. Concurrent current administration of tetracycline may alter the GI flora, decreasing the conversion of digoxin to DRPs. In these patients this could produce an increase in plasma digoxin concentration. The effect of tetracycline on the metabolism of digoxin to DRPs may persist for several months after the antibiotic is discontinued. Concomitant administration of tetracycline and digoxin increased the digoxin serum concentration 100%. (3)	DIGITEK, DIGOXIN, DIGOXIN MICRONIZED, LANOXIN
Coumarin Anticoagulants/Tetracyclines SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown. Tetracyclines may interfere with vitamin-K producing gut flora. CLINICAL EFFECTS: The addition of a tetracycline to a patient maintained on a coumarin anticoagulant may result in increased anticoagulant effects, including bleeding. PREDISPOSING FACTORS: he risk for bleeding episodes may be greater in patients with disease-associated factors (e.g. thrombocytopenia). Drug associated risk factors include concurrent use of multiple drugs which inhibit anticoagulant/antiplatelet metabolism and/or have an inherent risk for bleeding (e.g. NSAIDs). PATIENT MANAGEMENT: Patients maintained on coumarin anticoagulants should be closely monitored when tetracyclines are initiated and discontinued. The dosage of the anticoagulant may need to be adjusted. When applicable, perform agent-specific laboratory test (e.g. INR, aPTT) to monitor efficacy and safety of anticoagulation. Discontinue anticoagulation in patients with active pathologic bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling. The time of highest risk for a coumarin-type drug interaction is when the precipitant drug is initiated or discontinued. Contact the prescriber before initiating, altering the dose or discontinuing either drug. DISCUSSION: In a retrospective review of patients receiving either acenocoumarol or phenprocoumon, use of doxycycline and tetracycline was associated with relative risk of major bleeding of 3 and 9, respectively.(1) There are several case reports of bleeding following the addition of doxycycline(2-4) and tetracycline(5,6) to warfarin therapy.	DICUMAROL, JANTOVEN, WARFARIN SODIUM

Contraindication List
Pregnancy

Severe List
Clostridioides difficile infection
Idiopathic intracranial hypertension

The following adverse reaction information is available for SEYSARA (sarecycline hcl):

Overview
Severe
Less Severe

Adverse reaction overview.

The most common adverse effect of sarecycline is nausea, which was reported in 3-5% of patients in clinical trials.

There are 2 severe adverse reactions.

More Frequent	Less Frequent
None.	None.

Rare/Very Rare
Clostridioides difficile infection Intracranial hypertension

There are 7 less severe adverse reactions.

More Frequent	Less Frequent
Nausea	Skin photosensitivity Vertigo

Rare/Very Rare
Dental discoloration Dizziness Fungal infection Vulvovaginal candidiasis

The following precautions are available for SEYSARA (sarecycline hcl):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of sarecycline have not been established in pediatric patients younger than 9 years of age. The use of tetracyclines in pediatric patients younger than 8 years of age is not recommended due to potential for tooth discoloration. (See Dental and Bone Effects under Cautions: Warnings/Precautions.) The safety and efficacy of sarecycline for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in pediatric patients 9 years of age and older have been established by controlled clinical studies that included children in this age group.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Like other tetracyclines, sarecycline may cause fetal harm, permanent discoloration of teeth, and reversible inhibition of bone growth if administered during pregnancy. Human data are insufficient to inform a drug-associated risk for birth defects or miscarriage with sarecycline; however, tetracyclines are known to cross the placenta. If sarecycline is used during pregnancy or if the patient becomes pregnant while taking sarecycline, the patient should be apprised of the potential hazard to the fetus.

Because potential risks to the fetus outweigh potential benefits to the mother, pregnant patients should discontinue sarecycline as soon as pregnancy is recognized. In an embryofetal developmental study in rats, sarecycline administered to pregnant rats at oral dosages up to 500 mg/kg daily (7 times the maximum recommended human dosage (MRHD) based on area under the plasma concentration-time curve (AUC) comparison) during organogenesis was associated with decreased maternal body weight, fetal body weight, and litter size and increased numbers of resorption and postimplantation losses. Skeletal malformations (bent forelimb, hind limb, and scapula) were also reported at all dosage levels tested (50 mg/kg daily or higher; 1.4 or more times the MRHD based on AUC comparison).

In an embryofetal developmental study in rabbits, sarecycline was administered to pregnant rabbits at oral dosages up to 150 mg/kg daily during the period of organogenesis. Excessive maternal toxicity (mortality/moribundity/abortion) occurred at 150 mg/kg daily (5 times the MRHD based on AUC comparison) and this dosage group was terminated early. Maternal moribundity also occurred at 100 mg/kg daily (0.6 times the MRHD based on AUC comparison); no significant embryofetal toxicity or malformations were observed at dosages up to 100 mg/kg daily.

In a prenatal and postnatal developmental study in rats, sarecycline was administered to maternal rats at oral dosages up to 400 mg/kg daily during the period of organogenesis through lactation. Excessive litter toxicity (litter loss and stillbirth) occurred at 400 mg/kg daily (8 times the MRHD based on AUC comparison), which led to early termination of dams at parturition. Decreases in body weight and food consumption of dams during the lactation period occurred at 150 mg/kg daily (3 times the MRHD based on AUC comparison).

Decreases in offspring survival and offspring body weight during the pre-weaning and growth period, and decreases in implantation sites and viable embryos in female offspring occurred at 150 mg/kg daily (3 times the MRHD based on AUC comparison). However, no significant maternal or developmental toxicity was observed at 50 mg/kg daily (1.4 times the MRHD based on AUC comparison).

Tetracyclines are distributed into human milk. Because of the potential for serious adverse effects on bone and tooth development in nursing infants from tetracycline anti-infectives, women should be advised that breast-feeding is not recommended during sarecycline treatment.

There is insufficient experience in geriatric patients 65 years of age and older to determine whether they respond differently than younger adults. Clinically important age-related differences in the pharmacokinetics of sarecycline have not been reported when the drug was used in adults up to 73 years of age.